A formal total synthesis of (-)-cephalotaxine.
A formal total synthesis of (-)-cephalotaxine (1) has been achieved. The key step is an intramolecular aldol condensation of the diketone 9, which in turn was obtained in three steps from the azabicyclic compound 6 derived from D-proline according to Seebach's procedure. Treatment of 9 with a catalytic amount of sodium 2-methyl-2-butanolate in benzene at room temperature gave the alpha, beta-unsaturated ketone 8 in 43% yield. Catalytic hydrogenation of 8 followed by reduction of the ketone 22 with sodium borohydride and acetylation of the resulting alcohol 23 gave the acetoxy derivative 24, which, after deprotection, was acylated with (methylthio)acetic acid to give the amide 26. Compound 26 was converted into optically active ketolactam 4 following the synthetic operations developed for the synthesis of the racemic compound.
Ikeda
M
M
Kyoto Pharmaceutical University, Japan.
el Bialy
S A
SA
Hirose
K
K
Kotake
M
M
Sato
T
T
Bayomi
S M
SM
Shehata
I A
IA
Abdelal
A M
AM
Gad
L M
LM
Yakura
T
T
D000107:Acetylation; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis*; D001894:Borohydrides; D002384:Catalysis; D006248:Harringtonines / Q000138:chemical synthesis*; D000077863:Homoharringtonine; D007202:Indicators and Reagents
D000972:Antineoplastic Agents, Phytogenic; D001894:Borohydrides; D006248:Harringtonines; D007202:Indicators and Reagents; D000077863:Homoharringtonine; C025364:sodium borohydride