Asymmetric Total Synthesis
of Caribenol A
Author: Zhen Yang
J. Am. Chem. Soc. 2010, 132, 13608
Presented by
Daniel Roberts
April 6th 2014
Zhen Yang
Degrees
• 1978-82 B.S. Pharmaceutical Chemistry, Shenyang College of Pharmacy
• 1983-86 M.S. Pharmaceutical Chemistry, Shenyang College of Pharmacy
• 1989-92 Ph.D. Chemistry, Chinese University of Hong Kong
Academic Career
• 1992-95 Postdoctoral Fellow, Dept. of Chemistry, Scripps Research Inst.
• 1995-98 Assistant Professor, Dept of Chemistry, Scripps
• 2001-05 Institute Fellow, Dept. Cell Biology, Harvard Medical School
• 2002- Present, Changjiang Professor of Chemistry, Peking University
Honors
• 2000 The National Science Fund for Distinguished Young Investigator Award
(abroad), NSF of China (and 2004)
• 2005 Eli Lilly Scientific Excellence Award (China)
• 2009 Baogang Distinguished Teaching Award of Peking University
• 2010 Wuxi Pharma Life Science Excellence Award (Golden Metal)
1
Caribenol A
•
•
•
•
First isolated in 2007 from West Indian gorgonian octocoral
Shows strong inhibitory activity against mycobacterium tuberculosis
(H37Rv), which causes tuberculosis.
Caribenol A has an unprecedented tricarbocyclic ring system in that all three
methyl groups are cis and contains a 5 hydroxyfurnan motif
O
Chemically scarce
O
Me
Me
Me
OH
H
H
Me
2
RetroSynthesis
Carbenol A
O
O
O
O
Me
Me
Me
Me
H
Me
H
H
Me
Me
O
CO2Me
Me
TBSO
H
H
H
CO3Me
Me
Me
OH
O
Me
I
Me
Me
CO2Me
CO2Me
Me
O
TBSO
Me
Me
Me
H
3
Forward Synthesis
I
Me
Me
t-BuLi, Et2O
-78c
Me
Me CO Me
2
CO2Me
HO
O
LiBEt3H,THF
TBSOTf, Et3N
Me CO Me
2
PCC, CH2Cl2
Me
Me
O
Me
Me
O
Me
O
TBSO
Me
Me
4
Forward Synthesis
O
Me
Me
O
OH
Dibal, DCM
TBSO
Me
TBSO
-78c
Me
Me
Me
O
Me O
DMP, NaHCO3
rt
TBSO
Me
Me
CO2Me
O
HO
Me
n-BuLI, THF
-78c
TBSO
Me
Me
H
O
DMP, NaHCO3
rt
O
O
Me
TBSO
Me
Me
5
Forward Synthesis
O
Diels - Alder
O
O
Me
120c
Me
TBSO
Me
BHT
TBSO
Rh(PPh3)3Cl, H2
O
Me
TBSO
H
Me
Me
O
CO2Me
Me
CO2Me
Me
O
Me
HF/Py, THF
H
Me
HO
CO2Me
Me
H
Me
6
Forward Synthesis
O
Me
HO
CO2Me
Me
NaBH4
CeCl3 7H2O
EtOH
0c
H
O
O
Me
Me
H
HO
O
H
H
Me
O
O
Pd/C, H2,THF
Me
Me
H
H
Me
Me
O
KHMDS, THF
Comins Reagent
H
O
-78c
Me
Me
O
H
Me
O
TPAP, NMO,
4 A MS, DCM
O
Me
Me
H
TfO
H
H
Me
7
Forward Synthesis
O
O
O
Me
Me
H
TfO
rt
H
H
O
Pd(PPh3)4, Me2Zn, THF
H
Me
H
H
Me
Me
Me
Me
O
O
O
O2, DMF, K2CO3
Me
Me
O O
H
Me
H
60c, 80 hr
H
Me
O
P(OEt)3
Me
Me
OH
Me
H
H
Me
8
Finished
9