A synthesis of podophyllotoxin and several analogues is described. The key step that generates all four chiral centers of podophyllotoxin involves an intramolecular Diels-Alder reaction between an appropriately substituted o-quinodimethane and a pendant crotonate moiety. Thus trans-2-(3, 4, 5-trimethoxyphenyl)-4, 5-(methylenedi-oxy) benzocyclobutenol (7) was coupled with the isocyanate derived from methyl trans-4-aminocrotonate to yield ...
