1 OMICS International OMICS International through its Open Access Initiative is committed to make...
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1 OMICS International OMICS International through its Open Access Initiative is committed to make genuine and reliable contributions to the scientific community. OMICS International signed an agreement with more than 1000 International Societies to make healthcare information Open Access.
Transcript of 1 OMICS International OMICS International through its Open Access Initiative is committed to make...
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OMICS International
OMICS International through its Open Access Initiative is committed to make genuine and reliable contributions to the scientific community. OMICS International signed an agreement with more than 1000 International Societies to make healthcare information Open Access.
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Chemical Proteomic Special Training Program / Arrangement
Tao YE (葉濤 )
Hong Kong Polytechnic University
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Tao Ye received his B.Sc. (1983) and M.Sc. (1986) from East China University of Science & Technology. He obtained his Ph.D. (1993) from Queen's University, Belfast, under the supervision of Professor Tony McKervey. After pursuing a post-doctoral stay at QUB (1993-1994) and ROPA-postdoctoral work with Professor Gerald Pattenden at University of Nottingham (1994-1998), he joined the University of Hong Kong in 1998, then moved to The Hong Kong Polytechnic University in 2001 and was promoted to Associate Professor in 2005. He has completed the total syntheses of 38 marine natural products. He received "Xiaoyu Hu Memorial Award" (2014) and “WuXi PharmaTech Life Science and Chemistry Award” (2012), Asian Core Program Lectureship Award 2012 (To deliver a series of lectures in Japan) and Asian Core Program Lectureship Award 2012 (To deliver a series of lectures in Mainland China)
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Research Interests
Our laboratory is dedicated to the discovery and development of new agents of medicinal value. We are working in two main areas:
(1) Total Synthesis and Biological Evaluation of Natural Products and Their Analogues. Natural products have provided considerable value to the pharmaceutical industry over the past half century. In particular, the therapeutic area of oncology has benefited from numerous drug classes derived from natural product sources. In fact, over 60% of the anticancer agents approved have been of natural origin. Chemical synthesis of natural products and their analogues has been a key tool in drug discovery and development. The synthesis allows verification of primary structure proposed on the basis of studies of natural product, and presents opportunities to modify the structure, with the ultimate aim of improving activity or physicochemical/biological properties of the lead molecule. Synthesis is also crucial in the establishment of structure-activity relationships, as the ability to make analogues of the lead compound chemically is a prerequisite of such studies.
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We are particularly devoted to the exploration of natural-products-based novel antitumor agents. Large part of our research program is dedicated to the training and research in synthesis and biological evaluation of natural products with known anticancer activities.
(2) Design and Syntheses of Novel Small Molecule Bioprobes and Drugs. In the second area, our research centers on rationally designed molecular probes and their application to biological problems, especially in cancer biology and neurodegenerative disorders. Protein–protein interactions have a key role in most biological processes, and offer attractive opportunities for therapeutic intervention. The targeted manipulation of protein-protein interactions by small molecules is rapidly gaining importance in the development of biological tools for dissecting living processes on a molecular level and for the discovery of conceptually novel drugs. We have been focusing on the discovery of small molecules/peptidomimetics to prevent the degradation of p27, p53 and to regulate histone methylation process and epigenetic control.
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Recent Publications in Total synthesis of Natural Products: "Total Synthesis of Largamide B" Chem. Comm. 2015, 51, DOI: 10.1039/C4CC08901D "Total Synthesis and Stereochemical Reassignment of Mandelalide A", Angew. Chem. Int.
Ed. 2014, 53, 6533. "Synthesis of the Macrocyclic Core of Rhizopodin" Chem. Asian J. 2013, 8, 2955. "Total Synthesis and Biological Evaluation of Grassypeptolide A" Chem. Eur. J, 2013,
19, 6774. "Total Synthesis of Padanamides A and B"Chem. Comm. 2013, 49, 2977. "Total Synthesis and Stereochemical Revision of Lagunamide A" Chem. Comm. 2012,
48, 8697. “Total Synthesis and Absolute Configuration of Nocardioazine B” Chem. Comm. 2012,
48, 4344. “Total Synthesis of Hoiamide C” Org. Lett. 2011, 13, 2506. “Total Synthesis of Grassypeptolide” Chem.Comm. 2010, 46, 7486. “Synthesis of the Macrocyclic Core of Iriomoteolide-1a”Chem. Comm. 2010, 46, 4773. “Total Synthesis and Stereochemical Reassignment of Bisebromoamide” Org. Lett. 2010,
12, 3018. “Synthesis of the C9−C23 (C9’-C23’) Fragment of the Dimeric Natural Product
Rhizopodin”, Org. Lett. 2010, 12, 2036. “Total Synthesis of Sintokamide C” Org. Lett. 2010, 12, 1100. “Towards the Stereochemical Assignment of Natural Lydiamycin A” Chem. Comm. 2010,
46, 574. “Total Synthesis of Largamide H” Chem. Comm. 2010, 46, 153.
Structure elucidation of natural products Prior to the 1960’s, structure elucidation heavily relied on
chemical degradation or derivatization followed by partial or total synthesis.
Structure elucidation of increasingly limited quantities of components from marine natural product extracts heavily rely on advanced nano-scale NMR technologies.
Chemical degradation and derivatization were somewhat less involved.
Certain stereochemical issues are often difficult or impossible to be determined by spectral methodology alone
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Structure elucidation1. NMR based methods 1D and 2D NMR The 13C NMR acetonide method (Rychnovsky) Universal NMR database (Kishi) Chiral derivatizing agents (Mosher’s method) J-Based configurational analysis (Murata’s method)
2. Chiroptical methods Polarimetry UV-vis and electronic circular dichroism The exciton chirality method (Nakanishi) Infrared and vibrational circular dichroism
3. Chromatographic methods (e.g. Marfey’s method)
4. Biosynthetic methods
5. X-ray crystallography
6. Chemical synthesis including total synthesis
Stereochemical analysis methods
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Structures of Completed Natural Products:
Ceratospongamide
HN
O
HN
O
S N
OHO
O O O Cl Cl
SN
N N
SO
HN
N
O
HNN
O
NH
O
OO
O
NH
O
O O
NH
SN
SN
S
O
NO O
N
OO
HNO
HNO
HON
O
N
S
NH
OSN
N
O
Lyngbyabellin A
Largazole
Grassypeptolide
O
N
S
N
S
N
S O OH OHHN
O
OHO
Hoiamide C
NH
N
H
N
NO
HH
HO
Nocardioazine B
Padanamide A
O
O
HN
O
HO
O
NHN
HN
OH O
NH
NNH2
OO
HN
O
NH
OHN
OO
HN
O
NHO
O
Emericellamide A, n = 0Emericellamide B, n = 1
nO N
H
N
O
O
HN
OO O
NNH
O O
O
Pitipeptolide A
O O HN
OOH
O
O OH
HO
NH
O
O
N
S
N
S
N S
Hoiamide A
O
HN
O
ON
HNHN
NH
O
HO
OH O
HNO O
Padanamide B
Apd
HN
HNNH O
O
O
O
NH2
NH
O
O
H2N O
OHO
O
HN
O
N
NH
NH2
O
OHN
O
N
OHN
NH
HNO
NH
O
O
OH
HN OH
OMe
O
N O
O
ClCl
NHO
Cl
Cl
N
S N
NH
O
N
OMe
O Aeruginosamide
Largamide H
Sintokamide C Azumamide
NH
NH
HN
N
O
O
SS
12-deoxybionectin A
NH
NH
HN
N
O
OO
Gliocladin C
NH
NH
HN
N
O
O
S
S
Gliocladin B
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Structures of Completed Natural Products:
NHO
N
O
Br
OH
O
NS
NO
NH
O
NN
OO
Bisebromoamide
NN
NH
Ph
O
O
N
O
O O
O
HN O
O
O OH
NNH2
O
NO
NO
NO
O
NO
NH
O
NH
OH
O
HN O
HN
O NH
OHO
NH
O
HN
HN OH
O
N
O
CONH2
O
NH
OHN
OHO
HO
H2NOC
Dragonamide
Lagunamide A
Scytonemin A
Brukholdac A
Laxaphycin B
NH
HN
NH
HN
NH
O
O
HO
OO
ONH
O
HNO
O
O
O
OH
HO
Largamide B
O
NHHN O
S S
O
HN
OH
OO
S
Ph
NH
OH
O
HO
O
HN
O
O
NH O
HO
HN
O
O
NOH
N
O
OHO
HN
HN O
O
HN
OH
O
NH
Ph
NO
HN
HOO
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HN
O O
NH
OO
O
N
OO
NH
NH
H
O
OH
HO
MeO
Yanucamide A
Angelicastigmin
O
O
O
OH
O
O
OH
H
O
OMe
HOHO
Mandelalide A
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Structures of Completed Natural Products:
HN
OO
N
O
O
OOOHN
NH
OO
N
O
O
OO O NH
HN
HN
NH
O
OO
HN
HO
O
OH O
OCONH2
CONH2
O
N
O
OH
Celebeside C Onchidin
N
OO
O
O
ONO
O
HN
NO
Veraguamide D
NO
HN
N
O HN
OO
O
N
OO
N O
ClCl
Itralamide B
NH
N
O
NH
O
O O
O
NH
O
NN CO2H
HN
O O
NH
NH
N
NHO
OHO
O
O
NH
O
Ph
HN
NH
HN
O
HN
O O O
OHOH
OH
OH
H
Lydiamycin A Banyasin AIriomoteolide A
O
O
NH
HNNH
O
O
HN
O
O
O
OH
OH
LL15G256
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Current Targets
OMe
OOMe
MeO
OH
O OH OMe
NO
NO
OMe O
O
OMe
HO
OHOMe
NO
N O
OMeO
O
Rhizopodin
Actinoranone
NH
N
N
HN
O
OH
SnOH
Luteoalbustin A (n = 2)Luteoalbustin B (n = 3)
H
OH
OO
O
OO
OH
Br
OH
OH2N
O
Callyspongiolide
O
HO
O
H H
O
O
O
O
HO
O
O
OH
OMeHO
Mandelalide B
NH
N
O
KopsanoneCocosolide Looekeyolide C
Structures of cocosolide and looekeyolide C will be published in 2015
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