Synthesis of lignans related to the podophyllotoxin series

Abstract

The dibenzyl-γ-butyrolactone derivative (6), readily prepared by tandem conjugate addition to but-2-en-4-olide, undergoes cyclisation with trifluoroacetic acid to afford retrochinensin (10). After desulphurisation of (6) with Raney nickel, cyclisation yields the aryltetralin lactone (9). Treatment of (6) with concentrated perchloric acid gives a quantitative yield of the rearranged compound (11), which after appropriate modification can be cyclised to afford either the retro-dihydroarylnaphthalene lactone (13), or the 4-substituteed aryltetralin lactone (15). Extension of this approach to a second dibenzylbutyrolactone derivative (21) leads to the retro-dihydroarylnaphthalene lactone (25), but gives only a low yield of the required podophyllotoxin derivative (27).