Asymmetric total synthesis of (–)-podophyllotoxin

Abstract

(–)-Podophyllotoxin of 98% optical purity has been synthesized in eight steps and in 15% overall yield. The key step, Diels–Alder addition of the o-quinonoid pyrone 2 [6,7-methylenedioxy-1-(3,4,5-trimethoxyphenyl)-2-benzopyran-3-one] to the chiral dienophile 5 [5-(–)-menthyloxyfuran-2(5H)-one], proceeds with very high regio-, endo- and facial selectivity.