(–)-Phomoidride B (110108-TKGP) T.

Fukuyama1), 2)

O
O H
O H
O
O
O

O CO2H

Activity Ras farnesyl transferase inhibitor（Ras ファルネシル基転位酵素阻害剤)

(A) Evans aldol reaction, (B) intramolecular Diels-Alder reaction, (C) selective
Key Reactions esterification, (D) Arndt-Eistert homologation, (E) formation of anhydride via
carbonylation, (F) palladium-mediated coupling of thiolester

EtSH BuLi;
? ? CO2Me DBU
Br EtS ?
MeOH-H2O EtS
THF THF
1

###

BH3—Me2S ?
OH cat ? OH CSA DIBAL
O
MeO2C MeO2C OH
CO2Me THF acetone MeO2C O toluene

1) ? ?; ?;
Et2O-THF Et3N
O OAc O O
OHC O 2) Ac2O, pyridine O CH2Cl2-MeOH OHC O
DMAP
2

###

1) MsCl, Et3N
2) ?
HO EtCO2H LiAlH4 NaOEt, EtOH
EtO2C HO
? Et2O 3) LiCl, DMSO, ∆
B-91
∆

1) TsCl
LiAlH4 pyridine
EtO2C HO
Et2O 2) ?
DMSO
 t-BuLi;
CuI, HMPA EtS C8H15 EtS C8H15
?; Me2S; LHMDS;
C8H15
I MeO2C
I2 1, TMSCl ?
CO2Me CO2Me
THF
–78 °C to rt

Bn O

N Bn O
Bn O O
O ? O OH
O Et3N; 2 H
N
EtS C8H15 N
O
cat ? O EtS C8H15
MeCN, 50 °C O
MeO2C CO Me (A) O
2
MeO2C CO Me
2

1) ? O O
? O O
i-Pr2NEt Bn O O H ? O O H Ba(OH)2

2) ZnCl—OEt2 N THF EtS MeOH

pyridine EtS C8H15 0 °C EtS C8H15
O
CH2Cl2 O
MeO2C CO2Me MeO2C CO2Me
(B)

O ClCO2Me O
O Et3N O 1) ?
O H MeCN; O H K2CO3
HO2C MeO2C
aq NaHCO3 2) NaH;
EtS C8H15 EtS C8H15 p-O2NC6H4NTf2
(C)
MeO2C CO2H MeO2C CO2H

O
O O
O 1) Pd(PPh3)4 PhCO2Ag
OTf H
OTf H ?, ? Et3N
MeO2C
MeO2C
2) (COCl)2, ?; EtS C8H15 ?
EtS C8H15 ?, Et2O 50 °C
MeO2C (D)
MeO2C CO2Allyl
O N2
 Pd(OAc)2
O O (2-furyl)3P
O O i-Pr2NEt
OTf H 1) mCPBA OTfH ?, ?
MeO2C MeO2C
2) ? DMF, 90 °C;
EtS C8H15 ? O C8H15 aq HCl
B-37
MeO2C CO2t-Bu MeO2C CO2t-Bu (E)

O O H O
O O H
O O H OH ? O H OH
O H AcOH
O O
O O O C8H15 O
70 °C O C8H15
O C8H15
O CO2t-Bu O CO2t-Bu
MeO2C CO2t-Bu

O
1) (COCl)2 O H IZn
cat ? O SEt
CH2Cl2 H
?
O
2) EtSH O O C8H15 toluene
imidazole
CH2Cl2 (F)
O CO2t-Bu

O O
O H O H
O H O H
HCO2H
O O
O O
O O

O CO2t-Bu O CO2H
(–)-Phomoidride B

References:
1) N. Waizumi, T. Itoh, T. Fukuyama, J. Am. Chem. Soc., 122, 7825 (2000)
2) Y. Hayashi, T. Itoh, T. Fukuyama, Org. Lett., 5, 2235 (2003)