Hydrochloric Acid → Podophyllotoxin

Participants

Reaction Steps

The first synthesis of podophyllotoxin, compound 6 (Scheme 2), was reported by Gensler and coworkers [J. Am. Chem. Soc., 76: 5894 (1954); J. Am. Chem. Soc., 76: 315 (1954)]. ##STR13## Stobbe condensation of 1-(3',4',5'-trimethoxybenzoyl)-3,4-methylenedioxybenzene 26 with ethyl succinate followed by saponification and hydrogenation gave the saturated dibasic acid 27. Conversion to the anhydride followed by intramolecular Friedel-Crafts acylation and then esterification gave the cyclic keto-ester 28. Condensation with ethyl formate followed by sodium borohydride reduction and saponification afforded the dihydroxy acid 29. Treatment with 10% aqueous sulfuric acid gave α-apopicropodophyllotoxin 30 which was converted to picropodophyllotoxin 15 by treatment with dry HCl in glacial acetic acid followed by aqueous calcium carbonate.

Provenance & Evidence