Total syntheses of naturally occurring seimatopolide A and its enantiomer from chiral pool starting materials using a bidirectional strategy.

ABSTRACT

Enantioselective total syntheses of both enantiomers of the recently isolated decanolide natural product seimatopolide A are described. The C(2)-symmetric building blocks (R,R)-hexa-1,5-diene-3,4-diol (derived from D-mannitol) and its enantiomer (derived from l-(+)-tartrate) serve as key starting materials, which are elaborated in a bidirectional way using a selective mono-cross-metathesis, regio- and stereoselective epoxidation, and regioselective reductive epoxide opening to furnish the first fragment. Both enantiomers of the second fragment, 3-hydroxypent-4-enoic acid, were conveniently obtained through a lipase-catalyzed kinetic resolution and merged with the first fragment via Shiina esterification. An E-selective ring-closing metathesis was used to access the 10-membered lactone. A comparison of the specific optical rotations of synthetic seimatopolides with those reported for the natural product suggests that the originally assigned (3R,6R,7R,9S)-configuration should be corrected to (3S,6S,7S,9R).