The asymmetric synthesis of aryltetralin lignans: (-)-isolariciresinol dimethyl ether and (-)-deoxysikkimotoxin

The total asymmetric syntheses of (-)-isolariciresinol dimethyl ether (6) and(-)-deoxysikkimotoxin (7) have been carried out, in an attempt to exploit a synthetic strategy recently developed for the synthesis of (-)-deoxypodophyllotoxin (1, R(1) = -CH2-, Ar = 3,4,5-trimethoxyphenyl). In so doing, a generalized method for the synthesis of aryltetralin lignans has been developed that should be applicable to a variety of substitution patterns and stereochemistries. A one-pot, 100% regio-selective reduction-lactonization procedure has been developed for the conversion of the ester 18b to (-)-deoxysikkimotoxin, which gave 93% isolated yield in that step.