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(-) PLATENSIMYCIN
James MousseauMarch 3rd 2009
Ghosh, A. K.; Xi, K., J. Org Chem. 2009, 74, 1163-1170
O
ONH
OOH
OHHO2C
Wednesday, March 4, 2009
RETROSYNTHETIC ANALYSIS
O
ONH
OOH
OHHO2C
OH
NH2OH
TMSEO2C
+
O
OHO2C
O
EtO2COMe
O
H
Me
OMe
H
EtO2CO
H
Me
HOTBDPSO
O
(+)-Carvone
O
ONH
OOH
OHHO2C
Wednesday, March 4, 2009
O
ONH
OOH
OHHO2C
ONBS, THF-H2O
89%
O
OH
nBu3SnHAIBN, 80 ºC
Br
FRAI-DE
Two products (isomers)What are they?Mechanism?
Wednesday, March 4, 2009
O
ONH
OOH
OHHO2C
ONBS, THF-H2O
89%
O
OH
nBu3SnHAIBN, 80 ºC
Br
O
O
OH
HO
+
43%
42%
m-CPBADCM40 ºC
PASCALName of reaction?MechanismProduct
Wednesday, March 4, 2009
O
ONH
OOH
OHHO2C
ONBS, THF-H2O
89%
O
OH
nBu3SnHAIBN, 80 ºC
Br
O
O
OH
HO
+
43%
42%
m-CPBADCM40 ºC
OO
H
HO
OOH
1) m-CPBA2) KOH, then H2SO4
Wednesday, March 4, 2009
O
ONH
OOH
OHHO2C
OO
H
HO
1) Swern2) CF3CO3H
OO
H
OAc
1) K2CO32) TBSCl
OO
H
OTBS
83% over 4 steps
Cp2TiMe2toluene, 90 ºC
SEB V.Name of reactionProduct?Mech?
Wednesday, March 4, 2009
O
ONH
OOH
OHHO2C
OO
H
HO
1) Swern2) CF3CO3H
OO
H
OAc
1) K2CO32) TBSCl
OO
H
OTBS
83% over 4 steps
Cp2TiMe2toluene, 90 ºC
O
H
OTBS
9-BBN, H2O2
O
H
OTBS O
H
OTBS
55% 26%
+HH
HO OH
1) TBDPSCl2) DDQ3) Swern
O
H
TBDPSO
O
1) I2, PPh32) Zn, EtOH
HO OTBS
m-CPBAO
H
OTBS O
H
OTBS+HH
HO OH
1 1.3
Wednesday, March 4, 2009
TOWARDS TESTING D-A O
ONH
OOH
OHHO2C
O
H
TBDPSO
O
1) A, nBuLi2) DIBAL ANGELIQUE
Name of reaction?Mech?Product?
A
Ph
O
OP OMe
O
OMe
Wednesday, March 4, 2009
GAIS ASYMMETRIC HWE RXN O
ONH
OOH
OHHO2C
~95:5
Gais, H. J. et al. Liebigs, Ann., Recl. 1997, 2419-2431
Wednesday, March 4, 2009
TOWARDS TESTING D-A O
ONH
OOH
OHHO2C
O
H
TBDPSO
O
1) A, nBuLi2) DIBAL
A
Ph
O
O
OMe
O
OMe
O
H
TBDPSO
HO1) DMP2) WIttig3) TBAF
WILLIAMStructure of DMP?Mech of rxn?Final Product
Ph3P CH2
Wednesday, March 4, 2009
TOWARDS TESTING D-A O
ONH
OOH
OHHO2C
O
H
TBDPSO
O
1) A, nBuLi2) DIBAL
A
Ph
O
O
OMe
O
OMe
O
H
TBDPSO
HO1) DMP2) WIttig3) TBAF
O
H
HO
1) Swern2) Wittig
O
HO
O
HOHC
O
EtO2COMe
MesityleneBHT220 ºC
15%
CHO
O
20%
Wednesday, March 4, 2009
TOWARDS TESTING D-A
More Diels-Alder Testing.................
Methoxy group inhibited hydride shift
1 product obtained in 39% yield
O
ONH
OOH
OHHO2C
O
EtO2COMe
Wednesday, March 4, 2009
FINALLY DOING THE D-A O
ONH
OOH
OHHO2C
O
H
TBDPSO
HO 1) DHP, PPTS2) TBAF
O
H
HO
THPO1) Swern2) Wittig3) CSA
O
HHO
EtO2C
1) DMP2) Ph3P=CHOMe
O
H
EtO2C
OMe
1:1.5 E:Z
PhCl, BHT
270 ºCO
EtO2COMe
44%
- <7% of D-A Product of other isomer- SM recovered as 1:2.2 E:Z which can be re-isomerized and re-used
Wednesday, March 4, 2009
ENDGAME O
ONH
OOH
OHHO2C
O
EtO2COMe 1. LAH
2. DMP
3. KHMDS P(O)CH2CO2Et 18-c-6 O
OMeEtO2C
3:1 87%
Pd(OH)2H2, EtOH
O
OMeEtO2C
RuCl3, NaIO4CCl4, aq, MeCN
O
OEtO2C1) PhSeCl, HCl2) NaIO4SCOTT
Product?Mech?
Wednesday, March 4, 2009
ENDGAME O
ONH
OOH
OHHO2C
O
EtO2COMe 1. LAH
2. DMP
3. KHMDS P(O)CH2CO2Et 18-c-6 O
OMeEtO2C
3:1 87%
Pd(OH)2H2, EtOH
O
OMeEtO2C
RuCl3, NaIO4CCl4, aq, MeCN
O
OEtO2C1) PhSeCl, HCl2) NaIO4
O
OEtO2C
O
OHO2C
+
O OTMSE
HO
OHH2N
1) HATU, Et3N
2) TASF
O
ONH
OOH
OHHO2C
32 Steps OverallWednesday, March 4, 2009
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