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Banff Symposium on Organic Chemistry 2013 BSOC Participants, The BSOC organizing committee is gratified to welcome you to the 6th Banff Symposium on Organic Chemistry within the beautiful borders of Banff, Alberta! Banff Symposium on Organic Chemistry was established by a group of graduate students from the University of Alberta as a way to promote communication between graduate students, post-doctoral fellows, and internationally-renowned guest lecturers from academia and industry within a relaxing environment. Twelve years later, five universities from across western Canada collaborate to bring together new colleagues with new ideas, maintaining the same philosophy of informal networking and innovation between attendees. This year we are pleased to host some of the most prolific and recognized chemists the world has seen as keynote speakers: Dr. Paul Wender, Dr. Neil Garg, Dr. Suzanne Blum, Dr. Daniel Kahne, and Dr. Corey Stephenson. These talks will be complemented by presentations from promising graduate students studying at the University of British Columbia, University of Saskatchewan, University of Alberta, Simon Fraser University, and University of Calgary. With the great group of chemists we have assembled in mind, it could never have been achieved without our sponsors, listed within the abstract booklet. A huge thank you to all the sponsors for their support. Without further ado, I welcome you to BSOC 2013 in beautiful Banff and encourage you to make connections, live some chemistry, and relax in the Rocky Mountains. Sincerely, The BSOC Organizing Committee 2013 Amgad Albohy, Stanley Chang, Claire Chatalova, Colin Diner, Jinyue Ding, Christine Dunbar, Shira Halperin, Anushka Jayasuriya, Venkata Pavan Kumar Kondapi, Yonghoon Kwon, Verner Lofstrand, Nicole McNeil, Taras Rybak, Thomas Scully, and Jacky Yim

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Table of Contents

Welcome to BSOC Page 1

BSOC Schedule Page 3

Keynote Speakers

Professor Paul Wender Page 6

Professor Corey Stephenson Page 7

Professor Suzanne Blum Page 8

Professor Daniel Kahne Page 9

Professor Neil Garg Page 10

Abstracts

Oral Presentations Page 11

Poster Presentations Page 29

Participant List Page 56

Supplemental Information

Banff Town Map Page 61

Restaurants Page 62

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The 6th Banff Symposium on Organic Chemistry

Friday, November 8th, 2013

16:00 – 18:30 Hotel check-in and conference registration – Alpine Meadows Reception Area

19:00 – 19:15 Opening remarks – Summit Room

19:15 – 20:15 Keynote lecture – Professor Paul Wender

21:00 – 23:00 Opening mixer – Rose and Crown Pub

Saturday, November 9th, 2013

07:00 – 09:30 Breakfast – Glacier Salon

Morning session – Summit Room

(Chairs: Thomas Scully and Claire Chatalova)

09:30 – 09:50 Wenjie Shao

09:50 – 10:10 Samantha Keller

10:10 – 10:30 Bren Atienza

10:30 – 10:50 Eugene Chong

10:50 – 11:20 Coffee break

11:20 – 12:20 Keynote lecture – Professor Corey Stephenson

12:20 – 15:00 Lunch break

Afternoon session – Summit Room

(Chairs: Verner Lofstrand and Nicole McNeil)

15:00 – 15:20 Nargess Hosseini

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15:20 – 15:40 Ying Lau

15:40 – 16:00 Ho-Yan Sun

16:00 – 16:20 Natalie Campbell

16:20 – 16:40 Coffee Break

16:40 – 17:40 Keynote lecture – Professor Suzanne Blum

17:40 – 19:30 Dinner/sightseeing break

19:30 – 21:30 Mixer – Banff Ave. Brewing Co.

Sunday, November 10th, 2013

07:00 – 09:30 Breakfast – Glacier Salon

Morning session – Summit Room

(Chairs: Jinyue Ding and Jacky Yim)

09:30 – 09:50 Michael Holmes

09:50 – 10:10 Marcus Drover

10:10 – 10:30 Milan Bergeron-Brlek

10:30 – 10:50 Yonghoon Kwon

10:50 – 11:20 Coffee break

11:20 – 12:20 Keynote lecture – Professor Daniel Kahne

12:20 – 15:20 Lunch break

Afternoon session – Summit Room

(Chairs: Yonghoon Kwon and Stanley Chang)

15:20 – 15:40 Jinyue Ding

15:40 – 16:00 Claire Chatalova

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16:00 – 16:20 Colin Diner

16:20 – 16:40 Coffee Break

16:40 – 17:40 Keynote lecture – Professor Neil Garg

17:40 – 19:30 Dinner/sightseeing/poster set-up break

19:30 – 21:30 Poster session/mixer – Black Bear Room

Monday, November 11th, 2013

07:00 – 09:30 Breakfast – Glacier Salon

Morning Session – Summit Room

(Chairs: Colin Diner and Thomas Scully)

09:30 – 09:50 Jacky Yim

09:50 – 10:10 Nicole McNeil

10:10 – 10:30 Awards presentation and closing remarks

11:00 Hotel check-out

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Keynote Lecture

19:15 – 20:15 Friday, November 8th, 2013

Professor Paul Wender Bergstrom Professor of Chemistry, Stanford University Toward the Ideal Synthesis and Transformative Therapies Biography Professor Paul Wender obtained his bachelor’s degree in 1969 at Wilkes College. He received his doctorate degree in 1973 at Yale University, after which he completed a postdoctoral position at Columbia University. Professor Paul Wender’s research spans a variety of topics including chemistry, biology, medicine, and materials science. The Wender group has focused their research on the eradication of HIV/AIDS, multidrug resistance of chemotherapeutic drugs and the treatment of cognitive disorders. Among these contributions in medicinal chemistry, the Wender group has synthesized several chemotherapeutic drugs such as Taxol, Laulimalide and Bryostatin . The Wender group are interested in the invention of new reactions, such as the development of new transition metal-catalyzed reactions. Abstract Our research involves studies in chemistry, biology, medicine and materials science. A special emphasis is placed on synthesis-informed design directed at achieving improved or new function (Function Oriented Synthesis: Accts 2008, 40; PNAS 2011, 6721) in a step and time economical if not ideal fashion (Nature 2009, 197). This lecture will explore strategies to develop supply-impacting syntheses through the design of new reactions (JACS 2010, 2532), catalysts (ACIE 2012, 2736; JACS, 2012, 11012), drug delivery and nanoparticle technologies (PNAS 2012, 13171; Accts 2013, ASAP), and therapeutic leads, the last including a first-in-class strategy for the eradication of HIV/AIDS (Science 2008, 649; Nature Chemistry 2012, 705; PNAS 2013, 11698), a new approach for the treatment of Alzheimer’s disease and cognitive dysfunction (Neurobiology of Disease 2009, 332), and immunotherapeutic approaches to cancer that do not rely on cytotoxins (Clinical & Experimental Immunology 2009, 186).

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Keynote Lecture

11:30 – 12:30 Saturday, November 9th, 2013

Professor Corey Stephenson Associate Professor of Chemistry, University of Michigan Photochemical Approaches to Chemical Diversity, Complex Molecule Synthesis, and Biomass Degradation Biography Corey Stephenson obtained his B.Sc, Honours in Applied Chemistry at the University of Waterloo in 1998. He went on the complete a Ph.D. in Organic Chemistry under Peter Wipf at the University of Pittsburgh in 2004. Afterwards he completed a Postdoctoral Fellow at ETH- Hönggerberg under Erick Carreira. He us currently an Assistant Professor at University of Michigan. The Stephenson group is focused on methodology development, specifically the utilization of redox chemistry of visible light activated metal complexes, in order to access natural products. Moreover, the group is exploring the utilization of photocatalysts toward selective functionalization of organic molecules. These processes are aimed to improve chemoselectivity over current approaches, while enabling the reduction of stoichiometric waste byproducts. Abstract Photochemistry is a powerful tool to affect difficult bond forming events in the generation of architecturally fascinating small molecules. Despite providing rapid access to novel chemotypes and intellectual property space, it is remarkable that it is underutilized in the development of novel scaffolds and/or chemical synthesis outside of the academic community. This talk will describe our general program directed towards photochemical approaches to enhancing molecular diversity using both UV photochemistry and visible light mediated photocatalysis. Specifically, the photogeneration of reactive oxyallyl cations from readily available dienones and their intramolecular trapping with dipolarophiles along with the visible light mediated approaches to indole alkaloid synthesis and lignin degradation will be presented.

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Keynote Lecture

16:40 – 15:40 Saturday, November 9th, 2013

Professor Suzanne Blum Associate Professor of Chemistry, University of California at Irvine Dual-Metal Reactions with Gold & Microscopy for Organic Chemists Biography Professor Blum received her honours undergraduate degree in Chemistry at the University of Michigan in 2000. She obtained her Ph.D. at the University of California at Berkeley, where she studied under Dr. Bergman and Dr. Ellman. During her doctoral studies, she contributed to the study of organozirconium-mediated reactions. In 2004, she joined Professor Christopher Walsh at the Harvard Medical School, where she studied the mechanism of novel epimerase activity in the biosynthesis of syringomycin. Dr. Blum began her career as an assistant professor at the University of California in 2006. Her current research focuses on the development of single-molecule tools to study organic and organometallic reactions, to further the fundamental understanding of the reaction steps in catalytic systems. The Blum group is also working to develop and apply dual-catalyst systems for synthetic organic chemistry. Abstract Our research program is the mechanistic study of catalytic reactions, producing fundamental insights that lead to the development of new reactions and the improved selectivity of known reactions. Within this program, we have two main research thrusts: The first thrust is the development and fundamental study of dual-metal reactions, whereby two metals (or metalloids—i.e., boron) are employed to create new chemical bonds for organic synthesis; these reactions can be catalytic in both metals or catalytic in one and stoichiometric in the other. The second thrust is the development of fluorescence microscopy tools to revolutionize the tools for studying chemical reactions important to the field of synthetic chemistry and catalysis.

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Keynote Lecture

11:30 – 12:30 Sunday, November 10th, 2013

Professor Daniel Kahne Professor of Chemistry and Chemical Biology and Professor of Biological Chemistry and Molecular Pharmacology, Harvard University Lipopolysaccharide transport and assembly in Escherichia coli Biography Daniel Kahne received his B.Sc. from Cornell University in 1981, followed by his Ph.D. in 1986 from Columbia University under the supervision of Gilbert Stork. In 1988, he completed his postdoctoral work at Columbia University, where he worked as a synthetic chemist with Clark Still. Professor Daniel Kahne began his career as an assistant professor at Princeton University and remained as a faculty member for 16 years. In 2004, he moved to Harvard University, where his interests have been directed toward bacterial cell wall biosynthesis, specifically studying the molecular mechanisms by which antibiotics such as the beta-lactams, vancomycin and moneomysin interact with the enzymes that synthesize and degrade the bacterial cell wall. By increasing the fundamental understanding of bacterial cell envelope biogenesis, the Kahne group hopes to lay the groundwork for new antibacterial strategies. Abstract The outer membrane of Gram-negative bacteria contains an outer leaflet composed of lipopolysaccharide (LPS) that is transported to this location by a pathway that is essential for viability. It has been suggested that inhibitors of this pathway could be useful antibiotics. In Escherichia coli, eight essential proteins have been identified to function in the proper assembly of LPS following its biosynthesis. This assembly process involves release of LPS from the inner membrane, transport across the periplasm, and insertion into the outer leaflet of the outer membrane. I will talk about the mechanism of LPS transport and assembly and the development of tools that could lead to the discovery of inhibitors of this process.

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Keynote Lecture

16:40 – 15:40 Sunday, November 10th, 2013

Professor Neil Garg Professor of Chemistry, University of California at Los Angeles Complex Molecule Synthesis as a Fuel for Discovery Biography Professor Garg received a B.Sc. in Chemistry from New York University, where he did his undergraduate research with Professor Marc Walters. During his undergraduate years, he spent several months in France working as a research assistant with Professor Mir Wais Hosseini at Université Louis Pasteur. Garg completed his Ph.D. in 2005 from the California Institute of Technology under the supervision of Professor Brian Stoltz. During his doctoral work, Professor Garg succeeded in accomplishing the total synthesis of dragmacidin B, trans-dragmacidin C,and cis- and trans-dihydrohamacanthins A. He then joined Professor Larry Overman’s research laboratory at the University of California, where completed the total synthesis of (-)-Sarain A. Neil Garg began his career as an assistant professor at UCLA in 2007. The Garg group is primarily focused on the development of synthetic methodology. Professor Garg s also interested in the total synthesis of bioactive molecules such as Maoecrystal Z, Communesin A and Transtaganolide A. Abstract This presentation will describe my laboratory’s recent efforts to develop new tactics for the synthesis of complex organic molecules. In particular, new methods for the synthesis of functionalized heterocycles will be discussed. The application of these methods to the synthesis of intricate natural products such as the welwitindolinones will also be presented.

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O1 Oral Presentation

A General Route to 1,3'-Bipyrroles

Ping Cheng, Wenjie Shao and Derrick L. J. Clive*

Chemistry Department, University of Alberta, Edmonton, Alberta T6G 2G2, Canada

A general method is described for the synthesis of 1,3'-bipyrroles. The route involves constructing a pyrrole ring on the nitrogen of a substituted 1H-pyrrole, so as to generate the 1,3'-bipyrrole. In this approach the nitrogen of the starting pyrrole was alkylated with a special Michael acceptor having an allylic leaving group, and the product was then modified in such a way that the second pyrrole ring could be formed by a Paal-Knorr reaction. Two variants of this sequence were examined, one of which led to formation of a 3-hydroxypyridine instead of the second pyrrole ring; the other variant used phenacyl bromide instead of the special Michael acceptor.

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O2 Oral Presentation Tuning Light Absorption in Pyrene: Synthesis and Substitution Effects of Regioisomeric Donor–Acceptor Chromophores Samantha N. Keller, Nicole L. Veltri, Todd C. Sutherland Department of Chemistry, University of Calgary, 2500 University Drive NW, Calgary, AB, T3G1R8

Pyrene is well-known and loved as a photochemist’s molecule. Due to recent advances in synthetic chemistry allowing for its controlled and regioselective functionalization, pyrene is also gaining popularity as building block for small-molecule organic electronic devices such as transistors or photovoltaic cells. We have developed a synthetic strategy to access three regioisomers of a pyrene-based chromophore that feature strong charge transfer absorption bands due to the donor-acceptor (D-A) substitution pattern.1 These chromophores are non-fluorescent and absorb light in the long-wavelength region approaching 700 nm, making them promising light-harvesters for photovoltaic applications. Their optical properties depend greatly on the substitution pattern of the donor, but their electrochemical properties are relatively unaffected. In addition to the regiochemical relationship of donor and acceptor substituents, the nature and strength of the donor and acceptor can also be utilized to tune the light absorbing properties. Synthesis and characterization of new molecules illustrating this point will also be discussed.

OO

NN C12H25C12H25C12H25

C12H25

NNC12H25

C12H25C12H25

C12H25

OO

OO

NNC12H25

C12H25 C12H25

C12H25

1. S. N. Keller, N. L. Veltri, T. C. Sutherland, Org. Lett. 2013, 15, 4798-4801.

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O3 Oral Presentation

Redox Initiated Azide-Metallocarbene Coupling/Friedel-Crafts Cascade Reaction: Synthesis of Heteroaromatic Substituted 3-Indolone and Pyrrolidone Frameworks Bren Jordan Atienza and Frederick G. West* Department of Chemistry, University of Alberta, E3-43 Gunning-Lemieux Chemistry Centre, Edmonton, AB, T6G 2G2, Canada Copper(II) salts undergo reduction to Cu(I) in the presence of heteroaromatics via single electron transfer (SET) pathway producing oligomeric heteroaromatic compounds. Copper(I) catalyzes the intramolecular coupling of diazoketones with azides forming cyclic iminones. Sequential Friedel-Crafts alkylation to Brønsted acid activated iminones forms 3-indolone and 3-pyrrolidone structural motifs in one-pot under ambient conditions.

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O4 Oral Presentation Titanium Complexes of Pyridine Derivatives for the Synthesis of Amines Eugene Chong and Laurel L. Schafer* Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC, Canada V6T 1Z1 Cyclic amines and N-heterocycles are prevalent in biologically active compounds for agrochemical and pharmaceutical applications. The choice of catalyst between bis(2-pyridonate) and mono(2-aminopyridinate) titanium complexes can dictate the selectivity of the cyclization of primary aminoalkenes to give either hydroaminoalkylation (HAA) products from C–H bond addition across C=C bond or hydroamination (HA) products from N–H bond addition across C=C bond preferentially. Features of ligand design and modification of reaction conditions to favor either HAA or HA product formation will be highlighted.

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O5 Oral Presentation Expedient Route to Cyclobutanone Derivatives via the Stevens [1,2]- Rearrangement of Oxonium Ylides Using a Cyclopropylcarbinyl Migrating Group Seyedeh Nargess Hosseini and Frederick G. West* Department of Chemistry, University of Alberta, E3-43 Gunning-Lemieux Chemistry Centre, Edmonton, AB, T6G 2G2, Canada The Stevens [1,2]- rearrangement is a valuable carbon- carbon bond-forming process observed from ylide species.1 The intermediates are typically accessed from heteroatom attack on the in situ generated metallocarbenes using Cu and Rh catalysts. Designing a proper substrate possessing a potential migrating group enables organic chemists to synthesize valuable organic structures.2 We studied the role of the cyclopropylcarbinyl moiety as a migrating group in the Stevens rearrangement. It was found that migratory aptitude of the cyclopropylcarbinyl group affords strained cyclobutanone derivatives which can serve as valuable intermediate in the synthesis of biologically active compounds.3 As well, using a cyclopropylcarbinyl group as a radical clock4 provides insight into the controversial mechanism of the Stevens rearrangement to investigate whether [1,2]- Stevens rearrangement proceeds through a concerted mechanism or stepwise process involving either biradical or zwitterionic intermediate.

1. Murphy, G. K.; Stewart, C.; West, F. G. Tetrahedron 2013, 69, 2667. 2. a) Roskamp, E. J.; Johnson, C. R. J. Am. Chem. Soc. 1986, 108, 6062. b) Marmsäter, F. P.; Vanecko, K. A.; West, F. G.

Tetrahedron 2002, 58, 2027. 3. a) Rasik C. M.; Brown M. K. J. Am. Chem. Soc. 2013, 135, 1673 and references therein. b) Darses, B.; Greene, A. E.;

Coote, S. C; Poisson, J. F. Org. Lett. 2008, 10, 821. 4. a) Choi, S-Y.; Horner, J. H.; Newcomb, M. J. Org. Chem. 2000, 65, 4447. b) Le Tadic-Biadatti, M-H.; Newcomb, M. J.

Chem. Perkin Trans 2 1996, 1467.

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O6 Oral Presentation

Catalytic Asymmetric Synthesis of 3-Substituted Morpholines Ying Yin Lau, Huimin Zhai, and Laurel L. Schafer* Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada The synthesis of enantioenriched N-heterocycles typically requires the use of enantiopure starting materials, such as amino acids. However, we have recently disclosed the first catalytic approach for the enantioselective synthesis of 3-substituted N-heterocycles through a tandem sequential one-pot reaction employing both hydroamination and asymmetric hydrogen transfer reactions. Using aminoalkyne substrates, we utilize a commercially available bis(amidate)bis(amido)Ti precatalyst to yield a cyclic imine, which is subsequently reduced using commercially available RuCl [(S,S)-Ts-DPEN] (η6-p-cymene). For the synthesis of morpholines, excellent yields and enantioselectivities (up to >99%) were achieved. Using this general protocol, we have successfully extended this methodology to synthesize a variety of N-heterocycles, such as piperazines, thiomorpholines, and piperidines.

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O7 Oral Presentation Preparation of Chiral Organoboronates by Desymmetrization of 1,1-Diboron Compounds via an Asymmetric Suzuki-Miyaura Coupling Ho-Yan Sun, Dennis G. Hall* Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada Arguably one of the most prevalent approaches to carbon-carbon bond formation, cross-coupling reactions have received widespread attention over the years, which has led to the development of some of the most heavily used processes in pharmaceutical, materials and agrochemical industries.1 Among these processes is the Suzuki-Miyaura cross-coupling of organoboron derivatives. Despite numerous reports on the Suzuki-Miyaura cross-coupling of sp2-hybridized carbon centers, advances in the coupling of sp3 organoboronates, especially in a stereoselective manner, have been slow in comparison,2 due in part to problematic side reactions like β-hydride elimination and protodeboronation. As an effort to expand the available methods of cross-coupling alkylboronates, we are currently investigating the desymmetrization of prochiral 1,1-diboron compounds 1 through an asymmetric Suzuki-Miyaura cross-coupling. Initial studies have identified phosphoramidites 2 as a potentially suitable class of ligands for the transformation. The resulting chiral secondary organoboronates serve as useful synthetic building blocks as they are known to be capable of undergoing various transformations, allowing for a novel approach towards the construction of complex stereogenic centers. This method also has the potential to provide a unique way of accessing medicinally important diarylmethine units via sequential stereoselective Suzuki-Miyaura cross-couplings.

1 (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457; (b) Rudolph, A.; Lautens, M. Angew. Chem. Int. Ed. 2009, 48, 2656; (c) Molander, G. A.; Canturk, B. Angew. Chem. Int. Ed. 2009, 48, 9240. 2 For selected examples of stereoselective couplings of secondary organoboronates: (a) Imao, D.; Glasspoole, B. W.; Laberge, V. S.; Crudden, C. M. J. Am. Chem. Soc. 2009, 131, 5024; (b) Ohmura, T.; Awano, T.; Suginome, M. J. Am. Chem. Soc. 2010, 132, 13191; (c) Sandrock, D. L.; Jean-Gérard, L.; Chen, C.; Dreher, S. D.; Molander, G. A. J. Am. Chem. Soc. 2010, 132, 17108; (d) Lee, J. C. H.; McDonald, R.; Hall, D. G. Nature Chemistry 2011, 3, 894.

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O8 Oral Presentation Tandem Single-Electron/Pericyclic Cascade Process for the Synthesis of Dienes Natalie E. Campbell, Glenn M. Sammis* University of British Columbia, Rm D223-2036 Main Mall, Vancouver, BC, V6T 1Z1, Canada Dienes are integral motifs sought after in many natural product syntheses, present in either the desired final product or utilized within the synthetic design. Typically, cross-coupling strategies are used, however these are often difficult to incorporate due to their use of expensive metals or the complex syntheses of the reaction precursors. Using commercially available tosyl hydrazide, two fragments of varying complexity are able to be linked and, following reaction under radical conditions, nitrogen gas is expelled to generate a diene in high diastereoselectivity. This reaction can be employed to produce products with a range of substitution patterns. The proposed mechanism involves an initial one-electron radical addition process, followed by a subsequent pericyclic cycloreversion in one pot. Details of this mechanism and the tunability of this reaction will be discussed.

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O9 Oral Presentation Total Synthesis and Structural Revision of Laurefurenynes A and B Michael T. Holmes and Robert Britton* Department of Chemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC, V5A 1S6, Canada A total synthesis of the proposed structure of (–)-laurefurenyne A has been accomplished that relies on organocatalytic α-chlorination and a flexible chlorohydrin-based strategy for stereocontrolled access to the bis-tetrahydrofuran core of the natural product. Analysis of incongruities between the 1H NMR spectra of synthetic and natural material led to a configurational reassignment for the natural product, which was also confirmed by total synthesis.

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O10 Oral Presentation 3-Rhoda-1,2-diazacyclopentanes: A Unique Example of Diazene (RN=NR) Complexation and N-C Bond Formation at a Metal Centre Marcus W. Drover, Daniel W. Beh, Pierre Kennepohl, Laurel L. Schafer*, and Jennifer A. Love*

Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC, V6T 1Z1, Canada Metal-mediated N-C bond functionalization of dinitrogen has been a long-standing challenge.1 In our approach, we show that coordinated diazenes (RN=NR) are readily activated and subsequently functionalized using ethylene - a cheap and abundant C2 source employing a tetra-coordinate Rh complex.2 In particular, discrete Rh-containing metallacycles, [(TPA)RhIII(κ2-(C,N)-CH2CH2(NR)2-]Cl; TPA = N,N,N-tris(2-pyridyl)methylamine (such as [4]+) have been accessed through treatment of the rhodium(I) ethylene complex, [(TPA)Rh(η2-CH2CH2)]Cl ([1]Cl) with dinitrogen surrogates (RN=NR). Preliminary evidence using 2D NMR spectroscopy and ESI(+)-MS suggests that these moieties result from Rh-mediated N-N activation followed by ethylene insertion. We show this methodology to be tolerant of electron-deficient azo compounds, including several azo diesters (RCO2N=NCO2R; R = Et [2]Cl, R = iPr [3]Cl, R = tBu [4]Cl, and R = Bn [5]Cl) and a cyclic azo diamide, namely 4-phenyl-1,2,4-triazole-3,5-dione (PTAD = -C(O)N=NC(O)N(Ph)-) [6]Cl. The latter complex constitutes the first 3-metalla-1,2-diazabicyclopentane featuring two ortho-fused five-membered ring systems. Complexes [2-6]+ were characterized using a series of 1 and 2D NMR spectroscopic methods, including 1H-15N HMBC, to corroborate the formation of a five-membered Rh,N-containing ring system. In the absence of crystallographic data, we also present the DFT evaluation of these structures using geometry structure optimizations. Reactivity of these diazarhodacycles was also examined using a variety of acids. Notably, exposure of [4]Cl to trifluoroacetic acid, resulted in deprotection generating an ethyl functionalized, end-on coordinated diazene [8]+ - a hitherto unexplored motif.

(1) a) Knobloch, D.J.; Benito-Garagorri, D.; Bernskoetter, W.H.; Keresztes, I.; Lobkovsky, E.; Toomey, G.; Chirik, P.J. J. Am. Chem. Soc. 2009, 131, 14903. b) Morello, L.; Love, J.B.; Patrick, B.O.; Fryzuk, M.D. J. Am. Chem. Soc. 2004, 126, 9480. (2) Drover, M.W.; Beh, D.W.; Kennepohl, P.; Love, J.A. Chem. Sci. 2013, submitted

N

N NRh

N

+

[1]+N

N NRh

N

NN

HH

+

RN NRN

N NRh

N

NN

RR

+

CF3CO2H

HN NH

R = CO2tBu [4]+ [8]+

- 78 oC rt

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O11 Oral Presentation

De Novo Synthesis of Carbohydrates Analogues through Tandem Organocatalytic α-Chlorination-Aldol Reaction Milan Bergeron-Brlek and Robert Britton* Department of Chemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC, V5A1S6, Canada.

The aldol reaction is a powerrful tool in synthetic organic chemistry. Recently, we have discovered a one-pot tandem organocatalytic α-chlorination-aldol reaction that proceeds with dynamic kinetic resolution and provides ready access to choropolyols with excellent diastereoselectivity (2 :1 to 22 :1 dr) and enantioselectivity (up to 98% ee). Both chloropolyols diastereomers of these reactions give avvess to a variety of carbohydrate analogues in a short synthetic sequence with excellent stereocontrol and good yields. The discovery of this process and its application to the rapid synthesis of various carbohydrates will be presented.

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O12 Oral Presentation Further Studies of the Interrupted Nazarov Reaction Initiated by Organoaluminum Y. Kwon and F. G. West*, Department of Chemistry, University of Alberta, E3-43 Gunning-Lemieux Chemistry Centre, Edmonton, AB, T6G 2G2, Canada We have found that organoaluminum species can trigger the electrocyclization of dienone 1, and intercept the intermediate 2, intramolecularly, via ligand tranfer.1 The resulting aluminum enolate 3 can further react with an electrophile, expanding substituent patterns of cyclopentanone 4 with three new bonds formed in one pot. This talk will present studies on the functionalization of the Nazarov intermediate with various electrophiles, such as paraformaldehyde, triplet oxygen, and diiodomethane.

1) Y. Kwon, R. McDonald, F. G. West, Angew. Chem. Int. Ed. 2013, 52, 8616-8619.

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O13 Oral Presentation Concise Synthesis of All Mefloquine Stereoisomers Using a Highly Enantioselective Pd-Catalyzed Borylative Alkene Isomerization Jinyue Ding, Dennis G. Hall* Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada Malaria is a potentially fatal disease caused by Plasmodium parasites, which, according to the latest estimates,1 almost half of the world’s population is in danger of contracting. Moreover, the rapid evolution and adaptation of malaria parasites make drug resistance a continuing problem. As a leading antimalarial drug, mefloquine remains effective against all existing human malaria parasites.2 However, its clinical utility is plagued with the risk for severe neurotoxic side effects.3

Studies have shown that (+)-erythro and (+)-threo mefloquine have the same levels of IC50 against malaria parasites, and they are more active than their respective enantiomers,4 while (−)-erythro mefloquine can cause severe psychotropic effects. Lariam®, the marketed antimalarial formulation, contains the racemic (±)-erythro mefloquine, and thus contains both active and harmful forms of the drug. To the best of our knowledge, use of the threo enantiomers has never been explored for treating malaria, which maybe due to a more difficult synthetic access. Herein, we describe a concise and scalable synthesis of six mefloquine analogues, using a carefully optimized Pd-catalyzed asymmetric borylative alkene isomerization in tandem with stereoselective aldehyde allylboration.5 The resulting mefloquine stereoisomers/analogues were tested against Plasmodium falciparum NF54. The threo enantiomers and the two novel dehydromefloquine enantiomers displayed potent antimalarial activities, which confers to these analogues potential to be developed as alternative antimalarial drugs.

1 Murray, C. J. L.; Rosenfeld, L. C.; Lim, S. S.; Andrews, K. G.; Foreman, K. J.; Haring, D.; Fullman, N.; Naghavi, M.; Lozano, R.; Lopez, A. D. Lancet. 2012, 379, 413–431. 2 Schlagenhauf, P.; Adamcova, M.; Regep, L.; Schaerer, M. T.; Rhein, H-G. Malaria J. 2010, 9, 1–15. 3 a) Croft, A. M. J.; World, M. J.; Lancet 1996, 347, 326−326. b) Gullahorn, G. M.;; Bohman, H. R.;; Wallace, M. R. Lancet 1993, 341, 632−632. 4 a) Karle, J. M.; Olmeda, R.; Gerena, L.; Milhous, W. K. Exp. Parasitol. 1993, 76, 345−351. b) Schlagenhauf, P. J. Travel Med. 1999, 6, 122–123. 5 Lessard, S.; Peng, F.; Hall, D. G. J. Am. Chem. Soc. 2009, 131, 9612−9613.

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O14 Oral Presentation

Photochemical Decarboxylative Fluorination Claire Chatalova Sazepin and Glenn M. Sammis* Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC Canada V6T 1Z1

The introduction of fluorine into molecules often leads to interesting modification of their activity or properties. The vast majority of methods available for the incorporation of fluorine rely on the use of either electrophilic or nucleophilic fluorine. A third option, radical fluorination, was limited by the few available atomic fluorine sources, corrosive and/or expensive. We recently demonstrated the ability of two sources of electrophilic fluorine, N-fluorobenzenesulfonimide (NFSI) and Selectfluor® to efficiently transfer a fluorine atom to alkyl radicals.1

We then started to explore the scope of the radical fluorination and reported the synthesis of mono- and difluoroarylethers by photochemical decarboxylation fluorination.2 This process only requires irradiation in an alkaline solution. This methodology is currently being extended to the synthesis of trifluoromethoxyarylethers.

(1) Rueda-Becerril, M.; Chatalova Sazepin, C.; Leung, J. C. T.; Okbinoglu, T.; Kennepohl, P.; Paquin, J.-F.; Sammis, G. M. J.

Am. Chem. Soc. 2012, 134, 4026–4029. (2) Leung, J. C. T.; Chatalova Sazepin, C.; West, J. G.; Rueda-Becerril, M.; Paquin, J.-F.; Sammis, G. M. Angew. Chem. Int.

Ed. 2012, 51, 10804–10807.

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O15 Oral Presentation Synthesis of Archipelago Asphaltene Model Compounds Colin Diner and Jeffrey M. Stryker* Department of Chemistry, University of Alberta, E5-32 Gunning-Lemieux Chemistry Centre, Edmonton, AB, T6G 2G2, Canada While asphaltenes represent a major constituent of crude bitumen and are rich in potential chemical energy, they remain a difficult class of compounds to process into viable fuels due to their chemical complexity, heteroatom-rich constitution, and irreversibly aggregated molecular structure. Our goal is to reverse-engineer compounds that can be used as models for the types of chemical species hypothesized to populate bitumen. If these functionalized compounds prove to be good models for predicting asphaltene structure and behavior, they can be studied in well-defined systems to help understand how to increase the processing efficiency of crude bitumen. Due to the nature of the proposed downstream experiments, model compounds must be provided analytically pure and in gram quantities. Thus our synthetic strategies must be concise and chromatography-free.

Br ClEt Et

Et

Et

Et

Et

Br

Br

+

26

O16 Oral Presentation Bis(amidate)bis(amido) Titanium Complex: A Robust and Regioselective Intermolecular Alkyne Hydroamination Catalyst Jacky C.-H. Yim and Laurel L. Schafer* Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, B.C. Canada, V6T 1Z1 Nitrogen-containing organic molecules are ubiquitous in pharmaceuticals and agrochemicals, thereby making efficient, 100% atom economic C−N bonds forming reactions, such as hydroamination (the catalytic addition of an N−H bond across an unsaturated C−C bond), highly desirable. The Schafer group has previously reported a bis(amidate)bis(amido) titanium complex, which is now commercially available, as a regioselective alkyne hydroamination precatalyst. Exploration of substrate scope and regioselectivity regarding this complex will be presented. Modification to reaction conditions to allow for facile bench-top use is disclosed. Applications in tandem sequential reactions, with examples of allylamine and primary amine synthesis, and the assembly of a small library of aminoethers biologically active small molecule is presented.

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O17 Oral Presentation A Functionalized Cyclic Seleninate Ester: A Molecule of Many Talents Nicole M. R. McNeil, Marie C. Matz and Thomas G. Back* Department of Chemistry, University of Calgary, 2500 University Dr. NW Calgary, AB, T2N 1N4, Canada The hydroxymethyl functionalized cyclic seleninate ester (1) has proven to be a molecule with many interesting properties. This molecule displays glutathione peroxidise (GPx) activity and is therefore considered a GPx mimetic. GPx is a seleno-enzyme that catalyzes the reduction of peroxides in the presence of thiols. This seleno-enzyme is an important part of the defense mechanism against oxidative stress. GPx mimetics are valuable potential drug compounds that can be implemented during times of high oxidative stress when GPx can be overwhelmed by high concentrations of peroxides, such as during ischemic reperfusion of heart attack and stroke victims. In addition to its GPx activity, this compound displays interesting NMR properties resulting from its fluxional behavior at room temperature. Finally, en route to synthesizing this compound an unexpected re-arrangement was observed and the mechanism was investigated.1

1. Nicole M. R. McNeil, Marie C. Matz and Thomas G. Back, J. Org. Chem., 2013, 78 (20), 10369–10382

OSe

OOH

OSe

OO

Se

OH

OH

H2O2

heat

1

SeO

OH

O

1

OR

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P1 Poster Presentation Synthesis and Fluorous Binding Ability of Highly Fluorinated Glucose-Containing Oligosaccarides Santu Mandal, Todd L. Lowary*

Alberta Glycomics Centre and Department of Chemistry, University of Alberta, Edmonton, Alberta, T6G 2G2, Canada Fluorous phase chemistry is an emerging field in terms of new separation techniques. A highly fluorinated compound tends to dissolve in a fluorinated solvent rather than in a common organic solvent. Fluorophilic solid phase separation techniques are also well established. Our goal is to explore the fluorous binding ability of highly fluorinated cyclic and acyclic glucopyranoside oligosaccharides against fluorinated lipids. For this purpose we have selected two families of targets: cyclodextrins, α-(1→4)-linked cyclic glucose-containing oligosaccharides, and their open chain counterparts. Fluorinated cyclodextrins have previously been synthesized and shown to bind to p-trifluoromethyl phenol4 and inspiration for the latter class of compounds comes from bacteria. Some mycobacteria produce α-(1→4)-linked 6-O-methylated glucopyranose residues. These species form 1:1 complexes with long-chain fatty acids and acyl-coenzyme A derivatives in vitro.1 We envisioned that fluorinated derivatives of these molecules might bind to fluorinated lipids. We developed synthetic routes to prepare fluorinated oligosaccharides with variable number of glucopyranose residues.2,3 Highly fluorinated cylcodextrin derivatives have been synthesized earlier by other groups. Our synthetic scheme is focused on cyclodextrins as starting materials. Cyclic derivatives will be synthesized through a route that does not require protecting group chemistry. These cyclic molecules will serve as the precursors to the acyclic molecules through the use of a reported cyclodextrin cleavage method. These compounds will undergo binding affinity assays fluorous lipids using electrospray mass spectrometry.

1. Jackson, M. et al. J. Biol. Chem., 2009, 284, 1949 2. Hsu, M. C. et al. J. Org. Chem., 2007, 72, 1931 3. Meppen, M. et al. J. Org. Chem., 2007, 72, 1941 4. Becker, M. M. et al. Chem. Commun., 2010, 46, 4369

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P2 Poster Presentation

Efforts Towards Total Synthesis of Nosiheptide: Construction of the Pyridine Core Through a Modified Hantzsch Reaction Hee Jong (Jason) Hwang, Marco A. Ciufolini* Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia, Canada, V6T 1Z1

Efforts towards total synthesis of nosiheptide are described. A key phase of this endeavor is the construction of the heterocyclic core of the molecule through a modified Hantzsch reaction that delivers the complete pyridine segment in a convergent fashion. Thus, a delicate Michael addition merges fragments A and B to afford 1,5 diketone, which is then condensed with NH4OAc under an O2 atmosphere to furnish pyridine directly.

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P3 Poster Presentation Concise Synthetic Method for the Preparation of Substituted Indoles and Pyrrolopyridines Ying Zhu, Detian Gao and Thomas G. Back* Department of Chemistry, University of Calgary, 2500 University Drive NW, Calgary, AB T2N 1N4 , Canada

A novel, simple and efficient synthetic method for the preparation of variously functionalized and substituted indoles is described. It was achieved by the conjugate addition of N-formyl-o-haloanilines to acetylenic sulfones, esters and ketones. The resulting enamine adducts were then cyclized to the desired indoles by an intramolecular arylation reaction employing catalytic copper(II) acetate in DMF under ligand-free conditions without the need for exclusion of air and moisture. Numerous examples with good yield were reported.

The enamine first forms an isolable complex with Cu(II) and thus serves as the ligand for its own further transformation.The cyclization reaction then proceeds by reduction of Cu(II) to Cu(I) by formate ion produced by hydrolysis of the solvent, followed by Cu(I)-catalyzed ring-closure of the enamine. Interestingly ,this methodology can be extended to the preparation of functionalized and substituted pyrrolopyridines. Indoles and pyrrolopyridines are in turn common structural motifs of numerous alkaloids and medicinal compounds.

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P4 Poster Presentation

Studies Toward the Total Synthesis of Biselide A Matt Taron; Hope Fan; Baldip Kang; Rob Britton* Department of Chemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC, V5A 1S6, Canada Biselides and haterumalides are similar bioactive compounds that occur naturally in Okinawan marine invertebrates and were recently discovered in 2004. Biselide A has shown potent cytotoxicity against multiple types of human cancers, and has displayed no toxicity in vivo. While Biselide A harbours the potential as a novel anticancer drug, the synthesis of Biselide A would provide avenues for large scale synthesis, and to other promising derivatives that could be created. The total synthesis of haterumalides have been published numerous times, while the total synthesis of biselides have never been reported. The Britton group has been investigating the total synthesis of Biselide A and a recent change in strategy has shown promising results.

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P5 Poster Presentation

Computational Study of an Interrupted Nazarov Reaction Christine R. Dunbar, Yen-Ku Wu, and Frederick G. West*

Department of Chemistry, University of Alberta, E3-43 Gunning-Lemieux Chemistry Centre, Edmonton, AB, T6G 2G2, Canada

The interrupted Nazarov reaction between dienone 1 and furan was demonstrated to undergo [4+3] cycloaddition to give 2 using boron trifluoride etherate. However, under trimethysilyl triflate-mediated conditions, the Friedel-Crafts product 3 was obtained, with furan syn to the adjacent phenyl group. Experimental and computational evidence confirms that the formation of the cycloadduct under TMSOTf conditions is endergonic, whereas the formation of the cycloadduct under BF3•OEt2 conditions is exergonic. Additionally, a CH-π interaction between the furan and phenyl group is likely responsible for the selectivity in the formation of Friedel-Crafts product 3.

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P6 Poster Presentation New Niobium-Phosphoramidate Complexes for the Catalytic 𝜶-Alkylation of Secondary Amines Jason W. Brandt and Laurel L. Schafer* Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC, Canada V6T 1Z1 The transition-metal catalyzed -alkylation of amines, commonly referred to as hydroaminoalkylation, provides an atom-economic route to add complexity to amine substrates while avoiding the inefficiencies of stoichiometric reagents and protection/de-protection sequences found in conventional synthetic routes, such as N-alkylation or reductive amination procedures. The addition of phosphoramidate ligands to niobium-amido centers has led to the synthesis of new complexes that effect this transformation and provide increased reactivity compared to their tantalum analogues. Further, adjusting the steric parameters of phosphoramidate ligands leads to the spontaneous formation of bis(phosphoramidate) niobaziridine complexes that prove to be highly active in catalysis when compared to other isolated metallaaziridines.

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P7 Poster Presentation Synthesis of Nitrogen-Containing Sugar Nucleotides from Campylobacter Jejuni Ryan B. Snitynsky and Todd L. Lowary* Alberta Glycomics Centre and Department of Chemistry, University of Alberta, Edmonton, Alberta, T6G 2G2 , Canada The cell wall polysaccharides of pathogenic bacteria such as Mycobacterium tuberculosis and C. jejuni are essential for the virulence of these organisms. Many of these structures contain sugars in the five-membered (furanose) ring form, notable due to the absence of furanose sugars in mammals. For this reason, the inhibition of the bacterial enzymes that assemble cell wall polysaccharides has been suggested as a novel treatment for several diseases.1

The precursors of the sugars incorporated into cell wall polysaccharides are sugar nucleotides (e.g. 1, below), which are difficult to isolate in appreciable amounts from natural sources. Efficient routes to these precursors are required to study the glycosyltransferases involved in bacterial cell wall assembly. The syntheses of natural and non-natural sugar nucleotides are presented, outlining the formation of sugar-1-phosphates (2) and subsequent coupling with activated UDP derivatives. Efforts towards chemoenzymatic syntheses of these UDP-sugars using a nucleotidyltransferase enzyme2 (GalPUT) are also discussed.

Figure 1. Synthesis of sugar nucleotides to probe cell wall biosynthesis in C. jejuni. 1) Pedersen, L. L.; Turco, S. J. Cell. Mol. Life Sci. 2003, 60, 259–266. 2) Errey, J. C.; Mukhopadhyay, B.; Kartha, K. P. R.; Field, R. A. Chem. Comm. 2004, 23, 2706-2707.

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P8 Poster Presentation Novel Bioorthogonal Conjugation Based on ‘Click’ Boronate Formation Burcin Akgun, Sylvain Bernard and Dennis G. Hall* Department of Chemistry, University of Alberta, Edmonton, Alberta, T6G 2G2, Canada Bioorthogonal chemistry is the study of chemical reactions between biomolecules that occur without disturbing their natural biochemical processes (1a). This concept has become an important tool in proteomics to investigate biomolecules in their native state, to understand cellular events in real time, to enable drug discovery and the development of new biomaterials (1,2,3). To be considered a true bioorthogonal chemical reaction, the process must be rapid, selective and high yielding (1). ‘Click chemistry’, which refers to formation of substances rapidly and selectively by conjugating small/large molecules together, is the great answer for bioorthogonal reactions (1). The most widely studied ‘click’ reaction is copper-catalyzed azide-alkyne cycloaddition reactions discovered by Meldal and Sharpless (1,4). Unfortunately, the use of copper salts is a restrictive issue for in vivo applications due to its cytotoxicity. Recently, copper-free cycloaddition reactions have been investigated by employing strained alkyne substrates by Bertozzi and coworkers (1). This approach, however, has its disadvantages since the alkynyl substrates are less reactive towards azides, unstable and often challenging to synthesize (4). It has been previously reported by Brown and coworkers that pinanediol produces the most hydrolytically and oxidatively robust class of boronates (5). Biomolecules in living systems do not possess the class of 1,2-diols that are as rigid and as strongly binding as pinanediol. Thus, we propose novel copper-free click chemistry based on boronic ester formation to develop conjugates that are rapid, selective, stable and safe for in vivo applications and materials science.

1. (a) E. M. Sletten, C. R. Bertozzi, Angew. Chem. Int. Ed. 2009, 48, 6974-6998.(b) C. Hartmuth, C. Kolb, M. G. Finn, K.B. Sharpless, Angew. Chem. Int. Ed. 2001, 40, 2004-2021. (c) M. Morten, T. C. Wenzel, Chem. Rev. 2008, 108, 2952-3015. 2. J. Hou, X. Liu, J. Shen, G. Zhao, P. G. Wang, Expert Opin. Drug Discov. 2012, 7(6), 489-501. 3. M. D. Best, Biochemistry 2009, 48, 6571-6584. 4. (a) J. M. Baskin, C. R. Bertozzi, et al., PNAS 2007, 104, 16793-16797. (b) J. C. Jewett, E. M. Sletten, C. R. Bertozzi, J. Am. Chem. Soc. 2010, 132, 3688-3690. (c) J. C. Jewett, C. R. Bertozzi, Chem. Soc. Rev. 2010, 39, 1272-1279. 5. C.D. Roy, H.C. Brown, Monatshefte für Chemie 2007, 138, 879-887.

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P9 Poster Presentation Synthesis and Performance of an Alkylating Agent Sensor Philip A. Provencher and Jennifer A. Love* Department of Chemistry, University of British Columbia, Vancouver, BC, V6T 1Z1, Canada 4-(4-nitrobenzyl)pyridine (NBP) is a colorimetric indicator compound for many types of carcinogenic alkylating agents. It is used in toxicology screening of pharmaceutical compounds, detection of chemical warfare agents, environmental hygiene technology, and in other chemical analyses.

We report a novel and facile synthesis of the NBP-derivatives NBP-yde and NBP-Si from readily available salicylaldehyde and isoniazid, which allows for the incorporation of NBP through covalent bonds into a bulk material which is then sensitive to the presence of alkylating agents. NBP-Si has been integrated into a material known as a “sol-gel”, which is polymeric silica. This material changes color upon the exposure to dangerous alkylating agents like iodomethane. This material modernizes the NBP assay from a time consuming laboratory method to a real-time solid state sensor. This solid state sensor requires neither solvent nor additional reagents, and can detect gas-phase agents. NBP-yde and a number of other derivatives have been synthesized that may be incorporated into a variety of materials: a metal surface, a PEGylate, or organic based polymers. Additionally, these compounds could potentially be applied towards the synthesis of functional materials such as color switching material and dye sensitized solar cells. NBP is used extensively in preliminary tests for determining toxicology profiles and mutagenicity of medicinal compounds because of its similar reactivity to guanine in DNA. The compounds synthesized in this report address several problems with the use of NBP as a DNA model: (1) NBP-aci-K (synthesized from NBP-yde) is water soluble as opposed to the previous state of the art compound NBP, and thus may more closely reflect in vivo conditions, an important property in toxicology testing; (2) NBP-aci-K and NBP-yde both have reactive oxygen sites, which also improves the likeness of these compounds to DNA, since many hard carbocations react at oxygen in DNA; (3) the polymeric nature of the sol-gels synthesized more well reflect the sterics of DNA, which is a polymer.

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P10 Poster Presentation

Identifying the GalfNAC-Transferase in the Biosynthetic Pathway of Campylobacter Jejuni Strain NCTC11168 Capsular Polysaccharide Anushka B. Jayasuriya, Cory Q. Wenzel, Christine M. Szymanski, Todd L. Lowary. Alberta Glycomics Centre and Department of Chemistry, University of Alberta, Edmonton, Alberta, T6G 2G2, Canada

Campylobacter jejuni is currently the leading cause of food-borne gastroenteritis, and is a precursor to Guillian–Barré and Miller–Fischer syndromes (1). C. jejuni produces a number of unusual carbohydrates that are essential to viability and pathogenicity. Of particular interest is the C. jejuni serotype 11168 capsular polysaccharide (CPS), which in addition to having a structurally unique tetrasaccharide repeating unit (Figure 1), is an important virulence factor. Inhibitors of CPS biosynthesis are ideal therapeutic targets in circumventing diseases

associated with C. jejuni. However there remain many questions in regard to the mechanism of CPS biosynthesis, and without the proper identification of the enzymes that catalyze the synthesis of this tetrasaccharide, producing effective inhibitors remains problematic. This project aims to carry out investigations to identify the enzymes (glycosyltransferases, GTs) that catalyze the coupling of the carbohydrate residues in the tetrasaccharide repeating unit. We have focused initially on the enzyme that introduces the GalfNAc residue (Figure 1, ring C), GalfNAc-transferase. The sugar nucleotide donor substrate is UDP-GalfNAc (1, Figure 2); possible acceptors are either monosaccharides 3 or 4, or disaccharides 5 or 6. The current poster outlines: two synthetic routes toward the heptose (2, Figure 2), allowing access to acceptors 5 and 6 (3); the synthesis of glucuronic acids 3 and 4, in addition to their coupling with 2, yielding 5 and 6; the chemoenzymatic approach toward donor 1. Work towards identifying the GalfNAc-transferase will be discussed, including preliminary work on cloning and expression, in addition to examining the substrate specificity of the five putative GT’s (1).

1.) Mol. Microbiol. 2005, 55, 90. 2.)JBC 2010, 285, 493. 3.) Org. Lett. 2011, 13, 5290.

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P11 Poster Presentation An Enantioselective Synthesis Of BIRT-377 and its Enantiomer Aaron Johnson, Thomas G. Back* Department of Chemistry, University of Calgary, Alberta T2N 1N4 BIRT-377 (Fig.1) is a member of a class of hydantoins which have potent anti-inflammatory properties. It is an antagonist of lymphocyte function-associated antigen-1 (LFA-1) mediated cell adhesion which plays a critical role in leukocyte adhesion and therefore has potential as a therapeutic agent in the treatment of allograft rejection and autoimmune disorders including Crohn’s disease.1

NN

O

O

Cl

Cl

Br Figure 1

Our synthetic route to BIRT-377 and its enantiomer builds on our group’s previous work of enzymatic asymmetric hydrolysis and desymmetrization of diesters followed by the Curtius rearrangement to obtain α-quaternary amines (Fig. 2).2

MeO OMeO O

OMeHOOO

NPig LiverEsterase

CurtiusRearr. CO

OMeO

Br Br Br1 2 3 Figure 2

BIRT-377 was synthesised starting from half ester 2. Acid amide 4 was obtained through several functional group modifications. Subsequent Curtius rearrangement gave intermediate 5 which was subjected to intramolecular cyclization and N-methylation to afford BIRT-377 (Fig. 3).Ent-BIRT-377 was synthesised from 2 by a variation of this approach.

Figure 3

(1) Kelly, T. Aq.; Jeanfavre, D. D.; McNeil, D. W.; Woska, J. R., Jr.; Reilly, P. L.; Mainolfi, E. A.; Kishimoto, K. M.; Nabozny, G. H.; Zinter, R.; Bormann, B.-J.; Rothlein, R. J. Immunol. 1999, 163, 5173–5177. (2) Iosub, V.; Haberl, A.R.; Leung, J.; Tang, M.; Vembaiyan, K.; Parvez, M.; Back, T.G. J. Org. Chem., 2010, 75, 1612–1619.

39

N

S

N

S

OC12H25

OC12H25C12H25O

C12H25O

meso

Figure 1: Structure of meso-alkynyl dithiaporphyrin.

Figure 2: DFT calculation of Figure 1 HOMO.

Figure 3: UV-Vis absorption of figure 1.

P12 Poster Presentation Synthesis of Meso-Alkynyl Dithiaporphyrins for Organic Photovoltaic Applications Ryan P. Jansonius, Ashley D. Bromby and Todd C. Sutherland* Department of Chemistry, University of Calgary, Calgary, AB, T2N 1N4, Canada Dithiaporphyrins are large, organic, aromatic, heterocycles composed of two pyrrole and two thiophene units linked through methine bridges into one macrocyclic ring. Because of the high degree of conjugation, porphyrins are photochemically and electrochemically active. Porphyrins exhibit high molar absorptivities, low oxidation potentials and a small HOMO-LUMO energy gap. The electronic properties of dithiaporphyrins make these macrocycles suitable for many organic electronic applications, including solar light harvesting for photovoltaic devices.1,2,3 The already desirable electronic properties of porphyrins can be further improved through functionalization at the four meso-positions, shown in Fig. 1. In order for these molecules to be well suited for photovoltaic applications they must efficiently absorb the solar spectrum. Based on this criterion, meso-alkynyl functional groups were synthesized to increase the size of the aromatic core, which redshifts the onset absorbance and stabilizes the oxidized porphyrin. Previous research has explored functionalization at the meso-positions with phenylalkyl ether groups.1 Theoretically, these groups satisfy the desired criteria, where the phenyl ring expands the aromatic core; experimentally however, the steric hindrance between the meso-substituents and the aromatic porphyrin prevents meaningful electronic communication from occurring. To relieve the steric interactions, a series of meso-functional groups incorporating alkyne spacers were synthesized. DFT calculations (B3LYP/6-31G+(d)) (Fig. 2) support the hypothesis that alkynes will improve conjugation and electronic communication between the meso-positions and the aromatic core because the HOMO is delocalized over the entire system, as opposed to the N2S2 macrocycle. UV-Vis spectroscopy (Fig. 3) of a synthesized meso-alkynyl dithiaporphyrin showed a significant redshift of ~100 nm relative to analogous phenyl ether dithiaporphyrins. The high degree of conjugation and electronic communication observed is promising for photovoltaic applications. 1. Bromby, A. D.; Kan, W. H.; Sutherland, T. C. J. Mater. Chem. 2012, 22, 20611-20617. 2. Yella, A.; Lee H. W; Tsao, H. N.; Yi, C.; Chandiran, A. K.; Nazeeruddin, K.; Diau, E. W. G.; Yeh, C. Y.; Zakeeruddin, S. M.; Gratzel, M. Science. 2011. 334, 629-633. 3. Bromby, A. D.; Jansonius, R. P.; Sutherland, T. C. J. Org. Chem. 2013. 78, 1612-1620.

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P13 Poster Presentation

Rational Design of Aldol Reactions with Kinetic Resolution

Sushital Jana, Diptarghya Kundu, Mojtaba Biniaz, and Dale E. Ward*

Department of Chemistry, University of Saskatchewan, 110 Science Place, Saskatoon SK S7N 5C9, Canada

In a previous proof-of-principle study, we demonstrated that aldol couplings of chiral reactants (X = S) that proceed with kinetic resolution under substrate control can be rationally designed by applying the 'multiplicativity' rule [J. Org. Chem. 2009, 74, 4447; 2012, 77, 10789]. In principle, all possible stereoisomers of 3 should be available by appropriate manipulation of the stereocontrol elements (diastereoface selectivity, relative topicity). Towards that goal, a study on the effects of relative configuration, protecting group, and enolate type on the diastereoface selectivity of 1 (X = H, H) has identified conditions that result in highly diastereoselective aldol reactions with (±)-2 that should proceed with kinetic resolution. The adducts 3 are useful for polypropionate synthesis.

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P14 Poster Presentation Silver(I)-promoted Syntheses of Natural Products Containing 5,5-Spiroacetals Stanley Chang and Robert Britton* Department of Chemistry, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada

Spiroacetals are important structural motifs in several biologically active molecules. In particular, a growing number of 5,5-spiroacetal-containing fungal metabolites have been isolated that possess potential anti-inflammatory applications. While a large body of research in stereocontrolled spiroacetal syntheses currently exist, only one previous example of hemiacetal alkylation en route to spiroacetals has been reported. Herein we wish to describe the use of inexpensive silver(I) reagents in the construction of 5,7-, 5,6-, and 5,5-spiroacetal-containing molecules via hemiacetal alkylation. The optimized cyclization conditions were further applied to the total syntheses of cephalosporolides E and F, as well as studies toward the total synthesis of ascospiroketal A.

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P15 Poster Presentation A Novel Method for Stereoselective Access to Boron and Titanium Enolates Diptarghya Kundu and Dale E. Ward* Department of Chemistry, University of Saskatchewan, 110 Science Place, Saskatoon, SK, S7N 5C9, Canada

Directed aldol reactions, particularly those of boron and titanium enolates, are powerful methods for stereoselective synthesis. Because the relative topicity of these processes is strongly correlated with enolate geometry, reliable methods for stereoselective enolate formation are essential. Although ‘soft enolization’ approaches are by far the most popular, their substrate scope is limited by steric hindrance and incompatibility with the Lewis acidic reagents. We have found that (E)-enol borinates and (Z)-enol titanates can be generated in high yields with excellent stereoselectivities by metathesis of the corresponding Li enolates with titanium (IV) or boron halides (or triflates). Enolate isomerization is implicated because the results are independent of the starting geometry of the Li enolate. Mechanistic studies are underway.

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P16 Poster Presentation

Study of Biosynthetic Pathways of Polyindolenine Alkaloids Soo (Steve) Hur, David Vocadlo, and Robert Britton* Simon Fraser University, Department of Chemistry, 8888 University Drive, V5A 1S6 Chimonanthine is the building block of a series of natural products found within terrestrial plants including members of Psychotria in the family of Rubiaceae. Studies have shown that alkaloids containing the chimonanthine core display interesting analgesic, anti-cancer and anti-bacterial activities. I aim to develop new assays for the enzymes involved in the biosynthesis of chimoanthine-based compounds as well as to identify these enzymes to use as biocatalysts that can generate libraries of modified natural products. Here I report on the identification of suitable plants containing these enzymes and demonstrate feasibility of new assays by showing that feeding of plants with synthetic precursors leads to the production of labelled chimonanthine.

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P17 Poster Presentation New Methodology of Imine Formation form Metallocarbene with Azide Tianmin Niu, Tina M. Bott, Frederick G. West* Department of Chemistry, University of Alberta, W5-54 Gunning-Lemieux Chemistry Centre, Edmonton, AB, T6G 2G2, Canada

Electron-deficient metallocarbenes, generated catalytically in situ from diazocarbonyl precursors, can be trapped by simple organic azides to generate reactive C-acyl imines. This can be viewed as a “green” process, since the only by-products are two equivalents of N2 gas. We are currently examining a range of nucleophilic traps for these imines, which allow for the one-pot formation of amino acid derivatives. The potential for carrying this out as a multicomponent coupling, as well as asymmetric catalysis, is also under study and will be discussed.

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P18 Poster Presentation

Nickel-Catalyzed C-X (X = O,F) Activation Nicole A. LaBerge and Jennifer A. Love* Department of Chemistry, University of British Columbia, 2036 Main Mall , Vancouver, B.C., Canada V6T 1Z1

Nickel catalysis has recently received increased attention due to its high abundance, low toxicity, and inexpensiveness compared to platinum and palladium. Toward this end, the Love group has recently reported examples of nickel catalysts that overcome limitations of platinum in the generation of partially fluorinated biaryls.1 We have also developed a novel method for the generation of sp2-sp3 carbon-carbon bonds via the activation of aryl-fluorine bonds using NiCl2(PEt3)2 and benzyl zinc bromide (eq 1).2 The Negishi reaction tolerates a range of substrates, proceeds at ambient temperature and does not require elaborate reagent preparation. Currently, we are investigating the use of Nickel catalysts in decarbonylative cross coupling to bis(heteroaryl) motifs (eq 2). Preliminary results show that esters are viable aroyl cross coupling partners, reacting with boronic acids. Reaction optimization and substrate screening will also be discussed.

1. Sun, A.D.; Love, J.A. Org. Lett. 2011, 13, 2750-2753. 2. Sun, A.D. Leung, K. Restivo, A.D. LaBerge, N.A. Takasaki, H. Love, J.A. Chem.-Eur. J. 2013.

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P19 Poster Presentation Applications of Fluorinated Imine and Hydrazone in Heterocycles Synthesis Haibo Xie and Robert N. Young* Department of Chemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC, V5A 1S6, Canada

The performance of organofluorine compounds in all aspects of chemicals industry such as

materials, pharmaceuticals, agrochemicals, fine chemicals, is phenomenal. Organofluorine compounds are rare in natural products, but 20~25% of drugs in the pharmaceutical pipeline contains at least one fluorine atom. As the incorporation of fluorine and/or fluorine-containing groups into an organic molecule often drastically alters the chemical, physical, and biological properties of the parent compound, it is only logical to conclude that above modification necessitate the invention of novel reagents and materials endowed with fluorine imparting properties. As a matter of fact, extensive studies have been carried out in seeking new synthetic fluorination methodologies during the last 30 years.

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P20 Poster Presentation Synthesis of Novel Titanium Complexes and their Reactivity toward Catalytic C−O Bond Formation Scott A. Ryken, Ruth L. Webster, Laurel L. Schafer*

Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC, V6T 1Z1, Canada

N,O- and O,O-chelating ligands on early transition metals have been shown to be useful for mediating a variety of catalytic reactions. Pyridone, binaphthol, and biphenol proligands have been utilized, including modified proligands featuring variable steric and electronic properties near the coordinating heteroatoms. These ligands have been installed on titanium to form pyridonate, binaphtholate, and biphenolate supported complexes. Initial reactivity studies have been conducted toward C−O bond forming catalysis, including activation of carbon dioxide with epoxides to form both monomeric carbonate and polycarbonate products, as well as ring opening polymerization (ROP) of epoxides and intramolecular hydroalkoxylation of alkynes.

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P21 Poster Presentation The Synthesis of ABC-Transporter Dependent Pathway Oligosaccharides from Klebsiella pneumonia Ryan P. Sweeney and Todd L. Lowary* Department of Chemistry, University of Alberta, CCIS 4-014, Edmonton, AB, T6G 2G2, Canada

Figure 1.

Glycans are large, complex molecules, which leads to difficulty in their isolation. Therefore, investigating the role of glycans in biological processes rely on synthetic carbohydrate chemistry to make multi-milligram quantities. Our lab has shown that synthesizing large oligosaccharides is achievable1. Our targets are the lipid oligosaccharides involved in the ABC-transporter dependent bacterial LPS biosynthesis of Klebsiella pneumonia. In this pathway, large lipid oligosaccharides are synthesized and transported from the inner membrane to the cell’s surface.2 Many questions remain about this pathway, including how the chain length is controlled and the effect that has on the transport. We will synthesize 5 molecules [5, Figure 1], of varying repeating unit length (4, 8, 12, 16, and 20), from the building blocks 3 and 4, which will allow us to address the problems associated with increasing molecular size, and allow investigation into the ABC-transporter dependent pathway in bacteria, giving insight to how oligosaccharides are transferred from the inner cell to the membrane.

1. Joe, M.; Bai, Y.; Nacario, R. C.; Lowary, T. L. J. Am. Chem. Soc. 2007, 129, 9885-9901. 2. Greenfield, L. K.; Whitfield, C. Carbohydr. Res. 2012, 356, 12-24

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P22 Poster Presentation Synthesis and Structural Analysis of Homo-Oligoureas Based on a Constrained Bicyclic 𝜷-Amino Acid Christophe Andréa*, Baptiste Legranda, Emmanuel Wengerc, Claude Didierjeanc, Marie Christine Averlant-Petitb, Jean Martineza, Monique Calmes,a Muriel Amblarda. a Institut des Biomolécules Max Mousseron (IBMM) UMR 5247 CNRS-Université Montpellier 1 et 2, 15 Avenue Charles Flahault, 34093 Montpellier, France. b Laboratoire de Chimie-Physique Macromoléculaire, Nancy Université, CNRS, 1 rue Grandville, BP20451, 54001 Nancy Cedex 1, France. c Laboratoire de Cristallographie, Résonance Magnétique et Modélisation, Nancy Université, UMR7036 CNRS-UHP, Boulevard des Aiguillettes, BPP239, 54506 Vandoeuvre-Lès-Nancy Cedex, France. The field of foldamers has become an important area of chemistry over the years because of their particular structural and functional properties. They can support biological activities comparable to those of folding biopolymers and they also found applications in material sciences.1 Among the foldamers based on natural peptide sequences, β-peptides are the most widely studied systems. Although a higher level of helix stability was obtained upon homologation of -peptides, the resulting γ-peptides have not received so much attention. An elegant way for the construction of γ-peptide mimetics was the use of an urea linkage.2

Compared to γ-peptide, the additional nitrogen in the urea linkage promotes helix stabilization by introducing additional conformational restriction to the backbone and hydrogen bond donor sites. In this study, our aim was to design new oligomers able to display a well-defined secondary structure combining the benefit of a conformationally constrained cyclic β-amino acid and the bifidic hydrogen bonds stabilization brought by urea links. We selected the bicyclic β-amino acid (S)-ABOC, i.e. [(S)-aminobicyclo[2.2.2]octane-2-carboxylic acid], a β2,3,3-trisubstituted cyclic amino acid that we recently described its ability to induce a turn.3 To study the progressive folding of oligoureas derived from the ABOC motif, we prepared BAC oligoureas (Bicyclic Amino Carbamoyl oligoureas) of different lengths and we investigated their conformational preference by a combination of NMR and CD spectroscopy and X-ray crystallography.4 1 Martinek and al., Chem. Soc. Rev. 2012, 41, 687 ; Guichard and Huc, Chem. Commun., 2011, 47 5933 ; Gellman et al. Chem. Rev. 2001, 101, 3219. 2. Fischer and al., Angew. Chem. Int. Ed., 2010, 49, 1067. 3. André and al., Org. Lett., 2012, 14, 960. 4. André and al., Angew. Chem. Int. Ed., 2012, 51, 11270.

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P23 Poster Presentation New Noscapine Analogues: Synthesis and Biological Evaluation Peter E. Ghaly, Jack A. Tuszynski*, and Frederick G. West*

Department of Chemistry, University of Alberta, E3-43 Gunning-Lemieux Chemistry Centre, Edmonton, AB, T6G 2G2, Canada Noscapine, a phthalide isoquinoline alkaloid, was originally extracted from opium. It has been extensively used as a cough suppressant due to its low toxicity profile.1 In 1997, it was found to have potent anti-cancer activity targeting tubulin, the protein required for microtubule formation.2 Our collaborators in the Tuszynski group have developed a library of computationally designed noscapine analogues that are predicted to bind more effectively to tubulin.3 To validate this computational study, we are preparing several of the analogues predicted to have the strongest binding coefficients. As a preliminary step, we have prepared simplified models of compounds to optimize the synthetic sequence. Interestingly, preliminary biological evaluation indicates that one of these simplified compounds displays activity that is comparable or superior to that of noscapine.

1- Winter, C. A.; Flataker, L. Toxicol. Appl. Pharm. 1961, 3, 96-106. 2- Ye, K.; Ke, Y.; Keshava, N.; Shanks, J.; Kapp, J. A.; Tekmal, R. R.; Petros, J.; Joshi, H. C. Proc. Natl. Acad. Sci. U. S. A. 1997, 95, 1601-1606. 3- Alisaraie, L.; Tuszynski J. A. Chem. Biol. Drug. Des. 2011, 78, 535-546.

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P24 Poster Presentation A New Route to Cylindricine Alkaloids Based on Cyclisations of Acetylenic Sulfones Rohen Prinsloo, Kristen Clary and Thomas Back* Department of Chemistry, University of Calgary, 2500 University Dr. NW, Calgary, AB, T2N 1N4, Canada Alkaloids are naturally-occurring nitrogen containing compounds typically produced by both animals and plants as secondary metabolites. Many useful pharmacological applications of alkaloids have been identified making them of special interest in drug discovery. In particular, marine alkaloids have been relatively little studied and are therefore of special current interest. The cylindricine family are marine alkaloids that contain a structurally unique tricyclic motif, making them synthetically challenging and a target for several synthetic efforts. Our group has developed a variety of new cyclisations, using acetylenic sulfones that can be exploited in routes to diverse alkaloids. Our proposed synthesis makes use of a tandem conjugate addition/base-catalysed cyclisation sequence of acetylenic sulfone 7 with amine 8 to give 6. An intramolecular electrophilic cyclisation gave the tricylic core of the selenide 5. A seleno-Pummerer reaction to give aldehyde 3 or a selenoxide elimination to afford 4 will be followed by reduction or hydroboration from the less hindered face, respectively, to provide the corresponding hydroxymethyl substituent. Birch reduction and desulfonylation is then expected to furnish the desired product.

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P25 Poster Presentation

Generation of 1,2-Cyclohexadiene Derivatives via Base-Induced-Elimination Sida Zhou, Verner Lofstrand and Frederick G. West* Department of Chemistry, University of Alberta, E3-43 Gunning-Lemieux Chemistry Centre, Edmonton, AB, T6G 2G2, Canada Cyclic allenes are highly strained ring systems, and this novel structural feature indicates a potential toward unique reactivity in complex molecule synthesis. 1,2-Cyclohexadiene is known to be one of the most strained cyclic allenes and can be generated via various conditions.1 Base induced elimination is a mild method to generate 1,2-cyclohexadienes when there are suitably acidic protons present in the precursor. Our group intends to apply this method to generate and trap substituted 1,2-cyclohexadienes. We have developed optimized conditions for this process, and are currently investigating the scope of both inter- and intramolecular trapping reactions.

1. M. Christl, “Cyclic Allenes Up to Seven-Membered Rings” in Modern Allene Chemistry (Eds.: N. Krause, A. Stephen, K. Kashmi), Wiley-VCH, Weinheim, 2004, pp. 243–357.

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P26 Poster Presentation Discovery via Target-Guided Synthesis and Optimization of Insulin-Degrading Enzyme Inhibitors Damien Bosc,† Xavier Marechal,† Julie Charton,† Jane Totobenazara,† Florence Leroux,† Catherine Piveteau,† Wei-Jei Tang,‡ Benoit Deprez,† Rebecca Deprez-Poulain†

†a INSERM U761 Biostructures and Drug Discovery, b Faculté de Pharmacie, Univ Lille Nord de France, 3 rue du Pr Laguesse, c Institut Pasteur de Lille, IFR 142, d PRIM, Lille F-59000, France, ‡ Ben-May Institute for Cancer Research, The University of Chicago, Chicago, Illinois, USA. Insulin Degrading Enzyme (IDE) is a ubiquitous Zinc metalloprotease implicated in the clearance of numerous physiological peptides among which the β-amyloid peptide and insulin, respectively implicated in Alzheimer’s disease and Diabetes.1 Consistently, mutations leading to functional loss of IDE or deletion of the gene in rodents result in high levels of insulin, glucose intolerance and accumulation of amyloid in brain. Moreover genetic studies have shown that polymorphism on the IDE region of chromosome are associated with Type-2 Diabetes and Alzheimer’s disease.2-3

Drug-like tools to explore in depth IDE’s role are needed. We thus decided to use multicomponent in situ click chemistry to access new inhibitors of IDE. By this original orthogonal target-guided synthesis was found ligands of IDE. These ligands were the starting points for further optimizations that are presented here. Thus, following the identification of several ligands, we assessed the Structure-Activity Relationships in the series by synthesizing the 1,4- and 1,5 disubstituted triazoles and measuring their inhibition of IDE. The best inhibitor displays an IC50 A-β 16-23 of 300 nM and an IC50 insulin of 60 nM and has a Ligand Efficiency of 0.27. The X-ray structure of an inhibitor-enzyme complex shows that the molecule locks the enzyme in a closed conformation. By this original work was found the first drug-like zinc-binding inhibitors of this enzyme. Thus this work opens new avenues for both the study of the function of IDE and for the design of therapeutic interventions.

1) Duckworth, W.C. et al., Endocr. Rev. 1998, 19, 608-624. 2) Fawcett, J. et al., Diabetologia, 2009, 52, 1457-1460. 3) Zhao, Z. et al., Neurobiology of Aging, 2007, 28, 824-830.

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P27 Poster Presentation Synthesis of β-D-idopyranosides via a Di-inversion in 2,3-Di-o-sulfonyl-β-D-galactopyranosides Rachel Hevey, Chang-Chun Ling* Alberta Glycomics Centre, Department of Chemistry, University of Calgary, Calgary Alberta T2N 1N4 Idopyranosides are unusual sugars which exhibit conformational flexibility, as the chair conformer typically observed with other hexopyranosides forces the C-2, C-3, and C-4 substituents into an axial orientation. Idopyranose derivatives have been isolated as components of natural products, such as the 6-deoxy-β-D-ido-heptopyranose found in the capsular polysaccharide of Campylobacter jejuni, or the L-iduronic acids found in the glycosaminoglycan polysaccharides heparin, heparan, and dermatan. We have recently reported a facile method to obtain β-D-ido-pyranosides from 2,3-di-O-sulfonyl-β-D-galactopyranosides [1], which enables subsequent orthogonal protection and is the first reported method able to install the challenging β-1,2-cis glycosidic linkage for idopyranosides. The method relies on a regio- and stereoselective double inversion of the C-2 and C-3 positions on galactopyranose via a 2,3-anhydro intermediate to give a single product with the desired ido-configuration. The di-inversion proceeds via nucleophilic attack on the S-atom of the 3-O-sulfonate ester, and is facilitated by intramolecular coordination of the counter-cation [2]. We will present a summary of our efforts at elucidating this unique mechanism, and subsequent use of the synthetic method to generate potential antigens for use in a conjugate vaccine against C. jejuni, which aim to target the 6-deoxy-β-D-ido-heptopyranose repeating unit.

[1] R. Hevey, A. Morland, and C.-C. Ling. J Org Chem 77(16): 6760-6772 (2012). [2] R. Hevey, and C.-C. Ling. Org & Biomol Chem 11(11): 1887-1895 (2013).

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P28 Poster Presentation Function-Oriented Synthesis of Simplified Laulimalide-based Antimitotic Compounds Taras Rybak and Dennis Hall*

Department of Chemistry, University of Alberta, 4-025 Centennial Centre for Interdisciplinary Science, Edmonton, AB, T6G 2G2, Canada

Laulimalide has shown significant potency in treating diseases such as ovarian and breast cancer.1-3 This natural antimitotic compound also possesses activity against multidrug-resistant cells that are known to affect the efficacy of other related chemotherapeutic drugs.4 Through function-oriented synthesis and computational studies, two classes of Laulimalide analogues (1 and 2) were identified as possible potent mitotic inhibitors. Our efforts toward the construction of these templates for future diversification will be presented.

1 Kingston, D.G.I. J. Nat. Prod. 2009, 72, 507-515. 2 Hamel, E. et al. Mol. Pharmacol. 2006, 70, 1555-1564. 3 Gapud, E.J.; Bai, R.; Ghosh, A.K.; Hamel, E. Mol. Pharmacol. 2004, 66, 113-121. 4 Pryor, D.E. et al. Biochemistry 2002, 41, 9109-9115.

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Oral Presentations

O1 Wenjie Shao Alberta A General Route to 1,3'-Bipyrroles O2 Samantha Keller Calgary Tuning Light Absorption in Pyrene: Synthesis and Substitution Effects of Regioisomeric Donor–Acceptor Chromophores O3 Bren Atienza Alberta Redox Initiated Azide-Metallocarbene Coupling/Friedel-Crafts Cascade Reaction: Synthesis of Heteroaromatic Substituted 3-Indolone and Pyrrolidone Frameworks O4 Eugene Chong British Columbia Titanium Complexes of Pyridine Derivatives for the Synthesis of Amines O5 Nargess Hosseini Alberta Expedient Route to Cyclobutanone Derivatives via the Stevens [1,2]-Rearrangement of Oxonium Ylides Using a Cyclopropylcarbinyl Migrating Group O6 Ying Lau British Columbia Catalytic Asymmetric Synthesis of 3-Substituted Morpholines O7 Ho-Yan Sun Alberta Preparation of Chiral Organoboronates by Desymmetrization of 1,1-Diboron Compounds via an Asymmetric Suzuki-Miyaura Coupling O8 Natalie Campbell British Columbia Tandem Single-Electron/Pericyclic Cascade Process for the Synthesis of Dienes O9 Michael Holmes Simon Fraser Total Synthesis and Structural Revision of Laurefurenynes A and B O10 Marcus Drover British Columbia 3-Rhoda-1,2-diazacyclopentanes: A Unique Example of Diazene (RN=NR) Complexation and N-C Bond Formation at a Metal Centre O11 Milan Bergeron-Brlek Simon Fraser De Novo Synthesis of Carbohydrates Analogues through Tandem Organocatalytic α-Chlorination-Aldol Reaction

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O12 Yonghoon Kwon Alberta Further Studies of the Interrupted Nazarov Reaction Initiated by Organoaluminum O13 Jinyue Ding Alberta Concise Synthesis of All Mefloquine Stereoisomers Using a Highly Enantioselective Pd-Catalyzed Borylative Alkene Isomerization O14 Claire Chatalova British Columbia Photochemical Decarboxylative Fluorination O15 Colin Diner Alberta Synthesis of Archipelago Asphaltene Model Compounds O16 Jacky Yim British Columbia Bis(amidate)bis(amido) Titanium Complex: A Robust and Regioselective Intermolecular Alkyne Hydroamination Catalyst O17 Nicole McNeil Calgary A Functionalized Cyclic Seleninate Ester: A Molecule of Many Talents

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Poster Presentations P1 Santu Mandal Alberta Synthesis and Fluorous Binding Ability of Highly Fluorinated Glucose-Containing Oligosaccarides P2 Jason Hwang British Columbia Efforts Towards Total Synthesis of Nosiheptide: Construction of the Pyridine Core Through a Modified Hantzsch Reaction P3 Ying Zhu Calgary Concise Synthetic Method for the Preparation of Substituted Indoles and Pyrrolopyridines P4 Matt Taron Simon Fraser Studies Toward the Total Synthesis of Biselide A P5 Christine Dunbar Alberta Computational Study of an Interrupted Nazarov Reaction P6 Jason Brandt British Columbia New Niobium-Phosphoramidate Complexes for the Catalytic 𝛼-Alkylation of Secondary Amines P7 Ryan Snitynsky Alberta Synthesis of Nitrogen-Containing Sugar Nucleotides from Campylobacter Jejuni P8 Burcin Akgun Alberta Novel Bioorthogonal Conjugation Based on ‘Click’ Boronate P9 Philip Provencher British Columbia Synthesis and Performance of an Alkylating Agent Sensor P10 Anushka Jayasuriya Alberta Identifying the GalfNAC-Transferase in the Biosynthetic Pathway of Campylobacter Jejuni Strain NCTC11168 Capsular Polysaccharide P11 Aaron Johnson Calgary An Enantioselective Synthesis Of BIRT-377 and its Enantiomer

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P12 Ryan Jansonius Calgary Synthesis of Meso-Alkynyl Dithiaporphyrins for Organic Photovoltaic Applications P13 Sushital Jana Saskatchewan Rational Design of Aldol Reactions with Kinetic Resolution P14 Stanley Chang Simon Fraser Silver(I)-promoted Syntheses of Natural Products Containing 5,5-Spiroacetals P15 Diptarghya Kundu Saskatchewan A Novel Method for Stereoselective Access to Boron and Titanium Enolates P16 Soo Hur Simon Fraser Study of Biosynthetic Pathways of Polyindolenine Alkaloids P17 Tianmin Niu Alberta New Methodology of Imine Formation form Metallocarbene with Azide P18 Nicole LaBerge British Columbia Nickel-Catalyzed C-X (X = O,F) Activation P19 Haibo Xie Simon Fraser Applications of Fluorinated Imine and Hydrazone in Heterocycles Synthesis P20 Scott Ryken British Columbia Synthesis of Novel Titanium Complexes and their Reactivity toward Catalytic C−O Bond Formation P21 Ryan Sweeney Alberta The Synthesis of ABC-Transporter Dependent Pathway Oligosaccharides from Klebsiella pneumonia P22 Christophe André Simon Fraser Synthesis and Structural Analysis of Homo-Oligoureas Based on a Constrained Bicyclic 𝛽-Amino Acid P23 Peter Ghaly Alberta New Noscapine Analogues: Synthesis and Biological Evaluation P24 Rohen Prinsloo Calgary A New Route to Cylindricine Alkaloids Based on Cyclisations of Acetylenic Sulfones

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P25 Sida Zhou Alberta Generation of 1,2-Cyclohexadiene Derivatives via Base-Induced-Elimination P26 Damien Bosc Simon Fraser Discovery via Target-Guided Synthesis and Optimization of Insulin-Degrading Enzyme Inhibitors P27 Chang-Chun Ling Calgary Synthesis of β-D-idopyranosides via a Di-inversion in 2,3-Di-o-sulfonyl-β-D-galactopyranosides P28 Taras Rybak Alberta Function-Oriented Synthesis of Simplified Laulimalide-based Antimitotic Compounds

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Banff Town Map

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Restaurants

Please note: Conference ID must be shown to be eligible for discounts. Coffee and Snacks

1. Wild Flour Bakery

211 Bear Street #101 Banff, AB (403) 760-5074 10% discount

Lunch/Dinner

2. Balkan The Greek Restaurant 120 Banff Avenue Banff, AB (403) 762-3454 15% discount

3. Banff Ave Brewing Co 110 Banff Ave 2nd Floor Clocktower Village Mall Banff, AB (403) 762-1003

4. Rose and Crown

202 Banff Avenue Banff, AB (403) 762-2121 10% discount

5. Old Spaghetti Factory

317 Banff Avenue Banff, AB (403) 760-2779 10% discount

6. Magpie and Stump 203 Caribou Street Banff, AB (403) 762-4067 10% discount