(–)-Erinacine E (080913-TKGP) M.

Nakada1), 2)

H O
O OH
H OH

OH
H OH

Activity Selective -opioid receptor agonist（選択的-オピオイド受容体アゴニスト）

(A) asymmetric cyclopropanation, (B) stereoselective reduction,
Key Reactions (C) aldol reaction, (D) ring expansion reaction, (E) stereoselective
epoxidation,
(F) glycosylation, (G) benzoyl group migratory intramolecular aldol reaction

1) NaH, THF; B-55

CO2Et CH2=C(Me)CH2Br ? TsN3, Et3N
CO2Et SO2Mes
CO2Et 2) ?, ? THF MeCN
O
reflux

Bn Bn
O O
N N
N2 PhSH SPh Li
t-BuOK ?
SO2Mes ?
O CuOTf, toluene t-BuOH SO2Mes THF
(A) O

SPh SPh S(O)Ph CHO

HO(CH2)2OH TFAA
? ? Et3N

? O O CH2Cl2 O O CH2Cl2 O O
O CH2Cl2
B-37
1

OMe OMe BnO O BnO O

? 1) LiAlH4
MeO2C ?; MeO2C 2) NaH, BnBr baker's yeast

MeO MeI 3) ? H2O, 30 °C

MeO O HO
(B)

An
1) ? HO OH 1) ? OPMB
?, DMF CSA O O 1) ?
I
2) H2, Raney-Ni 2) ?, ?
2) TBSOTf
HO ? TBSO
i-Pr2NEt
TBSO
2
 OAc 1) ? OH 1) PMBCl OPMB
O O O
? NaH
PhS OAc PhS OPiv PhS OTES
2) PivCl 2) NaOMe
OAc DMAP OH 3) TESCl OPMB
imidazole
3

OPMB OPMB
HO
t-BuLi, 1 ? ?
2 ?
Et2O-THF OTBS ?, ? ? OTBS
O O
O O

OPMB OPMB OH
C-27 1) ? ?
1) ? t-BuOK ?; HMPA
H
2) Dess-Martin DBU THF, 0 °C
oxidn O OH
(C) 2) ? (B)
O O O

OH OH O O
1)
Li 1) Dess-Martin CO2Me
H ? H oxidn LHMDS

H 2) H2 H 2) SOCl2 H ? H
Pd/C pyridine;
O HO
TsOH

O I C-43 O O
CO2Me SmI2 1) TMSOTf
CH2I2 HMPA Et3N
CO2Me CO2Me
TBAF H THF H 2) ?; H
–78 °C ?
pyridine
(D)

OH OH
C-13
1) ? Dess-Martin
1) DBU ? OTBDPS oxidn
CH2OH
2) DIBAL H 2) TBDPSCl H O
imidazole
(E)

O O OH
1) DBU
OTBDPS benzene OTBDPS (R)-CBS OTBDPS

H O 2) Bz2O H BH3·Me2S H
pyridine OBz OBz
DMAP (B)
 OPMB OH
O O

O OTES O OH
3, MeOTf 1) TBAF
OPMB NH4Cl OH TESCl
MS 4A
OTBDPS OH
Et2O 2) TFA Et3N
H H
OBz OBz
(F)

OH OBz OBz
O O O

O OH 1) Bz2O, Et3N O OH Swern O O

OTES DMAP OTES oxidn OTES
OTES 2) aq citric acid
CH2OH CHO
H aq NH4Cl H H
OBz OBz OBz

H O H O H O
O OR OBz O OR OBz O OR
H H H O
DBU
O O
CHO benzene O
H H O H O O
Ph
R = TES (G)

H O H O
O OH O OH
H OH H OH
IBX Me4NBH(OAc)3
OH OH
CH2Cl2-DMSO AcOH-MeCN H
H O OH
(B)

(–)-Erinacine E

References
1) H. Watanabe, M. Nakada, J. Am. Chem. Soc., 130, 1150 (2008)
2) H. Watanabe, M. Takano, M. Nakada, J. Synth. Org. Chem., 66, in press (2008)