Paul Grieco Chemistry
39
The Chemistry of Prof. Paul A. Grieco Montana State University Prepared by Andy Diep Senior Medicinal Research Scientist Forest Laboratories, Inc
Transcript of Paul Grieco Chemistry
The Chemistry of Prof. Paul A. Grieco
Montana State University
Prepared by Andy DiepSenior Medicinal Research Scientist
Forest Laboratories, Inc
Paul A. GriecoRegents Professor of Chemistry and Biochemistry
Montana State University
B.A., Boston University, 1966;M.A., Columbia University, 1967;Ph.D., Columbia University, 1970;
NSF Postdoctoral Fellow, Harvard University, 1970-71.
AwardsCharles & Nora L. Wiley Award for Meritorious Research, 1999; ACS Award for Creative Work in Synthetic Organic Chemistry, 1991; ACS Arthur C. Cope Scholar Award, 1990; National Cancer Institute Merit Award, 1988; ACS Ernest Guenther Award in the Chemistry of Essential Oils and Related Products, 1982; Award of the Akron Section of the ACS, 1982; Member, Medicinal Chemistry Study Section, NIH, 1998-01; Chairman Medicinal Chemistry Study Section, NIH, 1999-01; Japan Society for the Promotion of Science Fellow, 1978-79; Alfred P. Sloan Fellow, 1974-76; Eli Lilly Fellow, 1973-75.
Since 1997 Paul Grieco has been at Montana State University, where he is now Regents Professor of Chemistry and Biochemistry. Before that, he was the Earl Blough Professor and chairman of the chemistry department at Indiana University. He has published more than 250 articles in scientific journals and received many major awards. He has mentored 98 Ph.D. students and 75 postdoctoral fellows in his career. His research interests are center on the invention of new reactions, methods development of medium effects in organic reactions, and strategies in organic synthesis of natural products.
TotalSynthesis
Natural product
New Strategies&
Tactics
Designed & Discovered methods
Selected Highlights
• Organic Synthesis in Water By Paul A. Grieco Published by Springer, 1998 ISBN 0751404101, 9780751404104
• Development of Cationic Diels-Alder Reaction in Highly Polar Media, Lithium Perchlorate in Diethyl Ether (LPDE) * [1,3]-Sigmatropic Rearrangement of Allyl Vinyl Ethers * Catalytic Acid in LPDE to Promote: # Intra / Intermolecular Imino Diels-Alder # Intramolecular Cycloaddition of Heteroatom-Stabilized Allyl Cations * Nucleophilic Substitution and Ring Opening via Silyl Ketene Acetal • Stereospecific Synthesis of Natural Products via Bicyclo[2.2.2]heptenone & Oxabicyclo[3.2.1]octenes as templates
• Total Synthesis of Natural Products
DiumycinolJOC, 1975, 40, 2261
MoenocinolJACS, 1975, 97, 1597
OH
OH
OO
CostunolideJOC, 1977, 42, 1717
OH
OHH
H
SireninJACS, 1969, 91, 5660
O
OH
H
O
TemisinJCS, CC,, 1978, 76
OO
OH
OH
OO
R
OH
O
O
TuberiferineJCS, CC, 1976, 582
Eriolangin / EriolaninJACS, 1978, 100, 1616 ibid.,1980, 102, 5886
O
OO
H
OH
O
VernolepinJACS, 1976, 97, 1612ibid.,1977, 99, 5773
O
HO
OH
OO
VernomeninJACS, 1976, 97, 1612ibid.,1977, 99, 5773
O
O
O
H
DamsinJACS, 1977, 99, 7393ibid.,1982, 104, 4226
O
O
O
H
AmbrosinJACS, 1977, 99, 7393ibid.,1982, 104, 4226
OO
O
O
H
Stramonin BJOC, 1978, 43, 4552
O
H
OH
O
O
HelenalinJACS, 1978, 100, 5946ibid.,1982, 104, 4233
O
H
RO
O
O
R=H: Mexicanin 1R=Ac: Linifolin A
TL, 1979, 3265
NS
NH2
O
H HOH
COOH
ThienamycinJACS, 1984, 106, 6414
Selected works (total synthesis) by the Grieco Group
CompactinJACS, 1986, 108, 5908
O
O
O
O
H
H
H
H
MeO
OMe
QuassinJACS, 1980, 102, 7586ibid., 1984, 106, 3539
O
O
OH
H
H
H
OH
OH
OH
CastelanolideJOC, 1982, 47, 601ibid., 1984, 49, 2342
OH
H
O
H
OH
OH
OH
O
De-A-quassimarinJOC, 1987, 52, 3346
OH
H H
H
O
EstroneJOC, 1980, 45, 2247
NH
N
O
O
O O
NH
CO2HH
H
H
CalcimycinJACS, 1982, 104, 1436
O
O
O
OH
OH
MethynolideJACS, 1979, 101, 4749
O
O
OH
O
O
OH
OH
(+)-TylonolideJACS, 1982, 104, 5781
O
OH
H
OH
OH
O
OOH
HO
H
PolyandraneJACS, 1999, 121, 9891
O
H
OH
O
OHO
CO2Me
H
OH
RO
O
O
H
Bruceoside CJACS, 1996, 16, 5316
R=H ; (-)-ChaparrinoneR=OH ; (-)-Glaucarubolone
JACS, 1993, 115, 6078
O
H
OH
OH
H
O
H
OH
OOH
R
OH
H
H
O
OH
OOH
(+)-des-D-ChaparrinoneJOC, 1998, 63, 5929
Selected works (total synthesis) by the Grieco Group
O
O
O
H
O
H
OH
H
H
H
HH
Ph
CO2H
H
n
Endiandric AcidSYNLETT, 1997, 493
LycopodineJACS, 1998, 120, 5128
S
N
O
O OH O
OH
O
(-)-Epothilone BCC, 1998, 1597
NN
H
O
EburnamonineJOC, 1994, 59, 7197
N
NH
H H
H
IbogamineJOC, 1994, 59, 6898TL, 1996, 37, 8289
NH
NH O
N
NH
O
OH
O
O
O
Br
(+)-JasplakinolideJACS, 1988, 110, 1630
NH
N
CO2Me
H
H
PseudotabersonineJACS, 1993, 115, 1164
C(19)-C(32)Scytophycin C
TL, 1998, 39, 1125OL, 2002, 2, 245
C(19)-C(27)Rifamycin S
OL, 2001, 3, 481
O
O
O
H
H
OH H
H
OH
HO
Laulimalide
Selected works (total synthesis) by the Grieco Group
NHH
H
H
O
O
OO
O
OHNH
O
O
AcO
OH OHMeO
O
O
OOH
OH
NCHO
OMe
OMe
OMeOMe
O
Organic Synthesis in H2O & Polar MediaLithium Perchlorate in Diethyl Ether
(LPDE)
Aqueous Intermolecular Diels-Alder ChemistryDienes with Dienophiles in H2O
JOC. 1983, 48, 3137CO2Na
O
OO
O
H
CO2Me
+1. H2O / r.t. / 1h
2. CH2N2 / 77%
CO2Na
O
OO
O
H
CO2Me
+ 1. H2O / r.t. / 7h
2. CH2N2 / 77%
NH3
O
O
MeON
OH
MeO
Cl-
+
H2O / r.t. / 20 h95%
Tetrahedron, 1986, 42, 2847
Methacrolein
H2O / 550 C 16 h
LiAlH4
THF/00 C
CO2Na CO2H
H
OOH
OH
J.Chem.Soc., Chem Comm, 1988, 500
Aqueous Intermolecular Diels-Alder ChemistryDienes with Dienophiles in H2O
Benzene
reflux / 72h 67%
HO
CHO
OMe
CO2Na H
OMe
H H
O
CHO
CO2Na
+ H2O
r.t. / 5 h 75%
HO
CHO
OMe
CO2Et H
OMe
H H
O
CHO
CO2Et
+
O
H
OH
OH
H
O
H
OH
OOH
JOC. 1983, 48, 3137JACS. 1990, 112, 9436JACS, 1993, 115, 6078
Chaparrinone
VernolepinO
OO
H
OH
O
JOC. 1984, 49, 5257JOC. 1983, 48, 3137JACS. 1980, 102, 782
Aqueous Intermolecular Diels-Alder ChemistryDienes with Dienophiles in H2O
CO2Na
BnO
CHO
OBn
H
OHC
NaO2C
O
OH
OBn
+ H2O 1. NaBH4
2. H+ / 91%overall
O
H
O
MeO
Reaction in Highly Polar Media (LPDE)Nucleophilic Substitutions of Ketene Acetals
TL, 1992, 33, 4735
OHOTBS
OMeO
OMe
(2 eq)
3.0 M LiClO4 in Et2O rt., 15 min / 86%
H
OH O
OMe
H
OTBS
OMe(2 eq)
3.0 M LiClO4 in Et2O rt., 15 min / 92%
OH O
OMe
O
OMe
OTBS
OMe
3.0 M LiClO4 in Et2O 75% 4 : 1
Reaction in Highly Polar Media (LPDE)Nucleophilic Substitutions of Indole
OH
OHNH OH
1.0 M LiClO4 in Et2O .01 (eq) HOAc
Indole / 1.5 h / 86%
NH
H
H
OHNHN
H
H
H
3.0 M LiClO4 in Et2O
Indole / 30 min / 97%
Yuehchukene
J. Chem.Soc.,Chem.Commun, 1993, 510
Reaction in Highly Polar Media (LPDE)[4+2] Cycloaddition
TL., 1993, 34, 7367
NHBOCO
O
O
O
O
O
H
NHBOC
O
O
O
H
NHBOC+
7.7 : 1
toluene
550 C / 7h 86%
+
NHBOCO
O
O
O
O
O
H
NHBOC
O
O
O
H
NHBOC+
41 : 1
5.0 M LiClO4- Et2O
rt ., 4h
+
N
OTBS
OTBS O
OMe NH
O
CO2MeOTBS
5.0 M LiClO4- Et2O
4h / 80%+
endo : exo 3 : 1
Reaction in Highly Polar Media (LPDE)Intra/Intermolecular Ionic Diels-Alder Reactions
Synlett., 1995, 1155
O O
H
O
H
O
H
5.0 M LiClO4- Et2O
.1 (eq) CSA / 16h 63%
+ +
endo : endo : exo 1 4 1
OO
H
O O5.0 M LiClO4- Et2O
.01 (eq) CSA / 2h 95%
OO OO
5.0 M LiClO4- Et2O
.01 (eq) CSA / 30 min 96%
+
Reaction in Highly Polar Media (LPDE)Intramolecular Diels-Alder reaction of Trienone
O
H
H
H
H
O
1.0 M LiClO4- Et2O
.1 (eq) CSA / 24h 70%
O O
H
H H
H
O
H
H H
H
O
H
H H
H
O
+
2 : 1
o-dichlorobenzene reflux / 40 h 53%
1. 2 %
1.0 eq Et2AlCl DCM / 24h
Acid catalyzed migration of the diene prior to [4+2] cycloaddition
Reaction in Highly Polar Media (LPDE)Heteroatom-stabilized Allyl Cations Cycloaddition
OH
O O
H
H H
H
O
H
H H
H
O+
3.0 M LiClO4- Et2O
.1 (eq) TFA / 24h 91%
+
4 : 1
JACS. 1996, 118, 2095
OH
O
H
H
H
H
O
3.0 M LiClO4- Et2O
.1 (eq) TFA / 24h 87%
Reaction in Highly Polar Media (LPDE)Heteroatom-stabilized Allyl Cations Cycloaddition
TL. 1998, 39, 7047OH
H
H
OH
MeOO
H
H H
OH
H
H
5.0 M LiClO4- Et2O
.1 (eq) TFA / 75%
OTBSSPh
OH
Ph
HH
SPhOH
H H
H
H
Ph
5.0 M LiClO4- Et2O
.1 (eq) CSA / 88%
Ph
H
O
H
TIPSOH
H
H
Ph
O
H
HTIPSO
5.0 M LiClO4- Et2O
.1 (eq) TFA / 90%
H
H
H
PhHH
HHO2C
Endiandric acid A Synlett., 1997, 493
Reaction in Highly Polar Media (LPDE)1,4-Addition of Silyl Ketene Acetal
O
OTBS
OMe
OTBS
O
OMe
+1.0 M LiClO4- Et2O
rt., 30 min / 87%
O
OTBS
OMe
OTBS
O
OMe
+5.0 M LiClO4- Et2O
rt., 1.5 h / 76%
TL. 1991, 32, 4665
Reaction in Highly Polar Media (LPDE)1,4-Addition of Silyl Ketene Acetal
OTBS
OMe
O
O
O
H
OMe
CO2Me
O
O
H
OMe
CO2Me
OTBS
CO2Me1.0 M LiClO4- Et2O
24 h / 93%
JACS. 1993, 115, 5841
Sesbanimide A
OTBS
OMe
O
OO
O
H
TBSO
O
OO
H
TBSO
OTBS
CO2Me
O NHOH
OO
O
O
OH
3.0 M LiClO4- Et2O
rt., 2h / 65%
J.C.S., Chem.Commun. 1992, 368
PERSPECTIVES INTOTAL SYNTHESIS
Diels-Alder ChemistryTotal Synthesis of Pseudotabersonine
(Retro Diels-Alder/intramolecular aza Diels-Alder sequence)
Pseudotabersonine
NH
N
CO2Me
H
H
A B
CB D
JOC, 1987, 52, 5746JACS. 1993, 115, 1164
Compound D is anticipated to undergo a tandem retro Diels-Alder / intramolecular aza Diels-Alder reaction under aprotic conditions.
NH
O
C3H7H
N+
NH
O
N
NO
N
bn
K-diisopropylamideTHF / - 780 C / 53%
-OTf
KO-t-Bu / THFBnCl / Bu4NI /24 h 65%
NH
O
NH
O
C3H7H
trans-2-hexenal
tol / Et3N / reflux 18 h / 65%
Diels-Alder ChemistryTotal Synthesis of Pseudotabersonine
JOC, 1987, 52, 5746JACS. 1993, 115, 1164
DE
NO
N
bn N
O
N
bn
N
N
H
H
bn
O
BF3OEt2 / tol1000 C / 2 h
-
Aza Diels-Alder61% / (1.5 : 1 ds)
Retro Diels-Alder
NH
NH
H
CHO
MeCN / Et3N 800 C
NH
N
CO2Me
H
H
Pseudotabersonine
FGH
I
• The use of cyclopentadiene as a protective group• Mixture of [E] is of no consequence, since both will be transformed into intermediate [H]• Pericyclic reaction Cascades: tandem retro Diels-Alder/intramolecular aza Diels-Alder sequence
Li
CH(OEt)2
N
N
O
CH(OEt)2
OH
H
H
bn
NO
CH(OEt)2bn
N+
H
NO
CH(OEt)2bn
N
Acetone/H2O TsOH
Ibogamine
Reaction in Highly Polar Media (LPDE)Application Toward the Synthesis of Ibogamine
N
NH
NH
NHCBz
H
CO2Me
NH
H
CO2Me
OH
NHCBz
1. 3 (eq) diborane / THF
2. base / H2O2 / 68%
Electrophilic substitution at C2 of N’-CBz-tryptamine employinghighly polar media (LPDE)
NH
NHCBzOH CO2Me
NH
NHCBz
H
CO2Me
+ 5.0 M LiClO4-Et2O.05 (eq) CSA / 60%
TL. 1996, 37, 8289
O
O
O
H
O
CO2H
MeO OH
CO2Me
Ibogamine
Reaction in Highly Polar Media (LPDE)Synthesis of Ibogamine
N
NH
N
NH
H
Epi-Ibogamine
NH
H
CO2Me
OH
NHCBz
OI+
OH O
CF3CF3
NH
H
CO2Me
O
NHCBz
/ DCM / 75%
NH
H
CO2Me
O
NHCBz
NH
NH
H
CO2Me
NH
NH
H
CO2Me
1. 10% Pd-C / THF-EtOH (1:1) cyclohexene
2. Na-cyanoborohydride / TFA 75% / ratio (1 : 2.4)
+
NH
NH
H
CO2Me
1. Pyrolysis at 2200 C2. LiAlH4 / THF / 6h
TL. 1996, 37, 8289
Eburnamonine
Reaction in Highly Polar Media (LPDE)Intramolecular Imino Diels-Alder: Total Synthesis of Eburnamonine
NN
H
ON
N
H
H
O
NN
O
JOC. 1994, 59, 7197
NO
Et
OO
SiMe3 N
Et
OO
SiMe3NH
O
N
Et
OO
SiMe3NH
EtO2C
TEOC
NH
EtO2C
TEOCethyl diazoacetate Cu / 1350C
64 % (1 : 1)
+
BF3OEt2 (cat)
DCM / 00C
Reaction in Highly Polar Media (LPDE)Intramolecular Imino Diels-Alder: Total Synthesis of Eburnamonine
JOC. 1994, 59, 7197
NH
EtO2C
TEOC
O
NHTEOC
O
O2N
NN
H
H
O
NN
O
N
O
O
NH
TEOCO
NHTEOC
O
O2N
NH
O
N
O
NH
TEOC WittigOlefination
N
O
NH
TEOC NN
O
BTAF / molecular sieves
THF / 8h / 81% (sensitive imine)
Reaction in Highly Polar Media (LPDE)Intramolecular Imino Diels-Alder: Total Synthesis of Eburnamonine
JOC. 1994, 59, 7197
NN
H
H
O
reflux / EtOHsulfuric acid
80%
NN
H
O
Eburnamonine
NN
H
H
O
NN
O
5.0 M LiClO4-Et2O10 mol % CSA / rt
96 %
Lycopodine
Reaction in Highly Polar Media (LPDE)Heteroatom-Stabilized Allyl Cation: Total Synthesis of Lycopodine
NHH
H
H
O
JACS. 1998, 120, 5128
OH
O
H
H
H
H
O
3.0 M LiClO4- Et2O
.1 (eq) TFA / 24h 87%
methodology toward the synthesis of lycopodine
O
O
OTBDPSI OTMS
O
O
OTBDPS
OH
O
O
OTBDPS
O
1.2 eq LDA / THF - 780 C
Reaction in Highly Polar Media (LPDE)Heteroatom-Stabilized Allyl Cation: Total Synthesis of Lycopodine
JACS. 1998, 120, 5128
O
Oi-Pr
OTBDPS
OB
SSi Ph
B
S
Si
Ph O
H
OTBDPS
O
Oi-Pr
OTBDPS
OBBN
S SiMe3
Ph
O
Oi-Pr
OTBDPS
SPhOTBSLi
Oi-Pr
OTBDPS
SPhOH
OTBS
4.0 N NaOH
syn elimination (E-diene)
Pearson'sallylborane
THF / -780 C
Reaction in Highly Polar Media (LPDE)Heteroatom-Stabilized Allyl Cation: Total Synthesis of Lycopodine
JACS. 1998, 120, 5128
Oi-Pr
OTBDPS
SPhOTBS
OHH
H
OTBS
iPr-O
OTBDPS
SPh
2.0 M LiClO4-Et2O10 mol% / TFA / 1h 66%
Tricyclic compound possessing the 40 carbon atom and all the necessary carbonatoms needed for elaboration of lycopodine
NHH
H
H
O
Lycopodine
H
H
OTBS
iPr-O
OTBDPS
SPh
H
H
OH OTBDPS
SPh
O
H
H
H
SPh
O
H
I
1. 1.0 N HCl / THF2. K2CO3 / MeOH / 16h
1. Grieco elimination2. TBAF / THF
3. MsCl / Et3N / DCM4. NaI / acetone / reflux
Reaction in Highly Polar Media (LPDE)Heteroatom-Stabilized Allyl Cation: Total Synthesis of Lycopodine
JACS. 1998, 120, 5128
H
H
SPh
O
H
I
HH
H
H
O
SH
Ph
SOPh
n-Bu3SnH / AIBNbenzene / reflux 65%
.
HH
H
H
O
SH
Ph
HH
H
H
H
AcO
ONH H
H
H
OAc
H
O1. Li(t-BuO)3AlH / THF / 12h 2. Ac2O / DMAP / DCM
3. TMSCl / NaI / H2O HgCl2 / CH3CN / 2h
1. NH2OH - HCl (2 eq) / EtOH NaOAc (5 eq) 2. SOCl2 / dioxane (Beckmann rearrangement)
Reaction in Highly Polar Media (LPDE)Heteroatom-Stabilized Allyl Cation: Total Synthesis of Lycopodine
JACS. 1998, 120, 5128
NH H
H
H
OAc
H
ONH H
H
HH
OH
N H
H
HH
O
Cl
Red-Al / benzene / 80% NCS / DCM / 30 min then TPAP / 30 min
N H
H
HH
O
Cl
1. AgBF4 / benzene (Stieglitz rearrangement)
2. NaBH3CN / MeOH
NHH
H
H
O
Lycopodine
Reaction in Highly Polar Media (LPDE)Direct Ring Opening of Oxabicyclo[3.2.1] Systems
& Its Application to Synthesis
OTBS
OMeO
OTBSOTBS
OTBS
MeO2C
5.0 M LiClO4- Et2O
80%
O
OTBSO
OH
O
OH1. 5.0 M LiClO4- Et2O i-Bu2AlH
2. H2O
OTBS
OTBS
MeO2C
OH
OH
MeO2C
1. TBAF / HOAc / THF / 60h
2. LiAl(O-t-Bu)3H / THF
OL. 2001, 3, 481OL, 2002, 4, 245
OH
OH
MeO2COH OO OO
CO2Allyl
OTr O OPMPTES
Rigid 7-membered ring allowed for selective protonation & reduction
Reaction in Highly Polar Media (LPDE)Direct Ring Opening of Oxabicyclo[3.2.1] Systems
(Synthesis of the C1 - C11 Fragment of Epothilone B)
S
N
O
O OH O
OH
O
1 3 5
8
11
Epothilone B
OTBS
OMeO
OTBS OTBS
OTBS
MeO2C
5.0 M LiClO4- Et2O
OTMS
OMeO
OTBDPS OTBDPS
OTMS
O
MeO
5.0 M LiClO4- Et2O
.05 (eq) TMSCl / 60%
The C4 quaternary carbon atom was established through ring openingreaction
Functionalized cycloheptadiene provided all the necessary carbon atoms needed for further elaboration into the C3 - C11 fragment of epothilone
S
N
O
O OH O
OH
O
1 3 5
8
11
Epothilone B
OTBDPS
OTMS
O
MeO
OH
O
MeO
O
OH
O
MeO
O HF / pyridine THF / 15 h / 94%
20 : 1
OH
O
MeO
O
OMe
COOHPh
O
O
MeO
O
O
OMePh
O
O
MeO
O
OMePh
OH DCC / DMAP DCM / 16 h 85% / 99% de
LiAlH(t-BuO)3
THF / - 780C 6h / 89%
• Selective protonation• (S)-O-methylmandelic ester served as a resolving agent, protecting group, and a leaving group for the latter stage• Reduction from the -face avoiding the diaxial hydrogens
S
N
O
O OH O
OH
O
1 3 5
8
11
O
O
MeO
O
OMePh
OH
OHO
O
OTBSO
O
Lithium Iodidepy / reflux / 24h 91%
1. TBSOTf / DCM 2,6-lutidine
2. PtO2 / H2 / EtOH 95%
OTBSO
O
OTBSOH
OH
OTBSO
OH
O OLiBH4 / THF- 500 C / 17 h 97% acetone / 9h
91%
* Dealkylation / SN2’ ring cyclization via lithium iodide* Selective oxidation of diols to cyclic hemiketal
S
N
O
O OH O
OH
O
1 3 5
8
11
OTBSO
OH
OH
OH
OTBS
OH
OTBSO+ OTBSO
O
OAr
O
O
O
OTBS
OH
1. m-CPBA / DCM / 4h2. LiAlH4 / THF / - 200C 81%
m-CPBA LiAlH4
Baeyer-Villiger oxidation of hemiketalOL. 2000, 2, 1717
OH
OH
OTBS
OH
OH
OTBS
O O
OMe
OTBS
O O
OMe
p-MeOC6H4CH(OMe)2
TsOH / benzene1. ArSeCN /n-Bu3P THF : py (1:1)
2. H2O2 / 87%
S
N
O
O OH O
OH
O
1 3 5
8
11* Grieco elimination to form the terminal olefin* Regioselective reduction of the acetal via DiBAlH* Chelation controlled aldol
OTBS
O O
OMe
OTBS
O OPMB
OTBS
OiPrOTBS
OPMB
O
O OH
1. i-Bu2AlH / DCM
2. Dess-Martin Me2AlCl (2.5 eq) DCM / -780C
NH
N
O
O
O O
NH
CO2HH
H
H NS
NH2
OCOOH
OH
CO2H
OH
OH
OH
The Chemistry of Bicyclo[2.2.1]heptenone:Application to The Total Synthesis of Natural Products
(for further reading)
O
O
O
H
O
H
OH
O
O
O O
Br
O
MeO
HelenalinJACS, 1978, 100, 5946ibid.,1982, 104, 4233
DamsinJACS, 1977, 99, 7393ibid.,1982, 104, 4226
12-MethylprostaglandinsJACS, 1976, 4111
CalcimycinJACS, 1982, 104, 1436
ThienamycinJACS, 1984, 106, 6414
Andy Diep
