J. Org. C h e m . 1992,57, 1514-1516
1614
Asymmetric Synthesis of (-)-Neopodophyllotoxin James L. Charlton* and Kevin Koh Department of Chemistry, University of Manitoba, Winnipeg, Manitoba, Canuda R3T 2N2 Received July 26, 1991
A five-step asymmetric synthesis of neopodophyllotoxin in 18%overall yield and optical purity >97%,starting from 6-(3,4,5-trimethoxybenzyl)piperonal(6) and the fumarate of (S)-methyl mandelate (8), is described.
Among the aryltetralin lignans isolated from nature, podophyllotoxin is one of the most well known because of ita antimitotic and the fact that two of its derivatives, etoposide1p3(VP-16-213) and teniposide1g2(VM26), are in clinical use as anticancer agents. Because of
Scheme I
H
Scheme I1
-
II t-BuLi
0 A
A?
\.cn.a*
OMe M~O V
Podophyllotoxin
R=
0
,Teniposide
O M OH
e
RrMe,Etoporide
H2 Ipd IC Ethyl Acetate room temp
