Stereoselective total syntheses of the norlignan derivatives (±)-tri-O-methylsequirin-B and (±)-tri-O-methylsequirin-C

Abstract

A total synthesis of the trimethyl ether of (±)-sequirin-B (2), a norlignan constituent of Sequoia sempervirens(Redwood) is described. 3′,4′-Dimethoxyacetophenone was converted into veratroylethylene (9) and thence into 2,2-dimethyl-4-veratroyl-1,3-dioxolan (12)via the diol (11). The glycidic acid (16) was obtained from (12) by Darzens condensation with benzyl chloracetate and hydrogenolysis of the resulting ester. Decarboxylationrearrangement of the glycidic acid was Stereoselective, providing the desired diastereoisomer (22)(>80%) of 2-(3,4-dimethoxyphenyl)-2-(2,2-dimethyl-1,3-dioxolan-4-yl)acetaldehyde (15). Reaction of (22) with p-methoxybenzylidenetriphenylphosphorane gave trans- and cis-(±)-tri-O-methylsequirin-C acetonides (24) and (25); the corresponding diols (8)[(±)-tri-O-methylsequirin-C] and (27) both cyclised stereospecifically in acid to (2). An alternative route to (8), with improved control over olefin geometry, employed addition of p-methoxy-phenylacetylene to (12), trans-reduction of the acetylenic bond, and removal of the tertiary hydroxy-group by reduction of its hydrogen sulphate ester with lithium aluminium hydride. The differing courses of acid-catalysed cyclisation of (±)-tri-O-methylsequirin-C and the related enol acetonide (33) are discussed.