Synthesis and antiproliferative activity of retroetoposide

Retro-4′-demethyl-4-epipodophyllotoxin 6 was synthesized in eight steps and 10% overall yield from 4′-demethyl-4-epipodophyllotoxin 12. Subsequent coupling of 22 with 1-O-trimethylsilyl-4,6-O-ethylidene-β- -glucoside 26 afforded retroetoposide 5 which is 10-fold less cytotoxic than etoposide against L1210 cell line.