T. Fukuyama, T.

Kan
ephedradine A (080801-TKGP)

OH

H
O
N
H O
O
H N
HN H
N
H

Activity hypotensive, 血圧降下

(A) C-H insertion reaction, (B) intramolecular ester-amide exchange reaction,

Key Reactions
(C) macrocyclization by Ns-amide, (D) Staudinger and aza-Wittig reaction

1)
Ar Ar HO N
1) ? B-116
C-024 B-117
OH ? O C-049 O Me O
2) ? 1) ?; ? OH DEAD, PPh3

2) NaClO2 O 2) ?
3) K2CO3 ?
Br OBn Br Ar = OBn Br B-055
Cl

Ar B-126 1) Ba(OH)2
H Ar N 2) ?, ? H Ar
O N2 N O O HO NNs O O
O TBDPSO
O Rh2(S-DOSP)4
O H O Me H O
O Me HN
3) K2CO3, PhSH
(A)
Br Br C-002 Br
OTBDPS

Ar H Ar
H
O O N
N
CO2Me
? CbzNClNa
H H O
O
?, ? OAc (DHQD)2PHAL,
OH ? K2OsO2(OH)4
(B) Br TBDPSO TBDPSO

CO2Me
 H Ar
O N
1) BnOH
H 1) PPh3, CCl4 PPh3, DEAD
O ?
OAc 2) HCO2NH4 2) NsCl, Na2CO3
OH TBDPSO Pd/C
CbzHN
CO2Me
Ar = OBn

H Ar H Ar
O B-079 O
N N
1) H O 1) CSA
H O HO OTBS 2) NsNH2
DEAD, PPh3, AcO DEAD, PPh3
OAc
CO2Me
TBDPSO H 3) HF
NsHN 2) ? CbzN TBDPSO
CO2Me 3) ? OTBS

H Ar C-065 H Ar H Ar
O O 1) ? O
N N 2) ? N
DEAD, PPh3 3) ?
H O H O H O
AcO AcO 4) LiOH N3
CO2Me CO2Me 5) pentafluorophenol CO2Pfp
H H WSC·HCl H
CbzN HO CbzN N CbzN
(C) N
NHNs Ns Ns
OBn OH

H Ar
B-101 H H
O O O
N N 1) KOH N
? H2O PhSH
H O H O H O
OPfp 2) ?
O O
H N N N
CbzN H H
N CbzN H HN H
(D) Ns N N
Ns H

References
1) W. Kurosawa, T. Kan, T. Fukuyama, J. Am. Chem. Soc., 125,
125 8112-8113 (2003).
2) W. Kurosawa, T. Kan, T. Fukuyama, Synlett, 1028-1030 (2003)
3) T. Kan, T. Fukuyama, Chem Comm, 353-359 (2004)