LIGNANES .15. 1ST TOTAL SYNTHESIS OF NATURAL (-)-ALPHA-CONIDENDRIN

(-)-alpha-Conidendrin 1 was synthesized according to a general reaction scheme that could be applied to other retrolignans as well. Thus, treatment of the optically active beta-benzyl-gamma-butyrolactone (R)-(+)-4 with NBS, followed with benzyl alcohol selectively introduced a benzyloxy group in the benzylic position and afforded the mixture of epimers 7. alpha-Alkylation of the lithium enolate of the corresponding silyl ethers 10, with O-benzylvanillyl bromide 11, gave the trans disubstituted lactones 13 (2 epimers). Catalytic hydrogenolysis (Pd-C) of 13 selectively split the aryl benzyl ether linkage, and gave the compounds 14. Intramolecular Friedel-Crafts cyclization of the latter, using the benzyloxy group as the leaving group, was induced with BF3.Et2O and afforded (-)-alpha-conidendrin 1 in 36% overall yield from methyl alpha-vanillylhemisuccinate (R)-(+)-17.