SYNTHESIS OF PODOPHYLLUM LIGNAN ANALOGS

Three podophyllotoxin analogues 1-3 having unsymmetrically substituted methoxyl groups in the pendant aryl ring have been synthesized by the application of tandem conjugate addition reaction. Piperonal propane-1, 3-dithiane, but-2-en-4-olide and 2, 3, 4-trimethoxybenzaldehyde furnish a lactone alcohol 5a, which upon desulphurization followed by cyclization yields 3-hydroxymethyl-6, 7-methylenedioxy-1-(2', 3', 4'-trimethoxyphenyl-1, 2, 3, 4-tetrahydro-2-naphthoic acid gamma-lactone 1. Cyclization of 5a followed by dethioketalization affords 3. The use of 2, 4, 5-trimethoxybenzaldehyde as substrate furnishes the aryltetralin lignan analogue 2.