A highly stereoselective and flexible strategy for the convergent synthesis of long-chain polydeoxypropionates: application towards the synthesis of the glycolipid membrane components hydroxyphthioceranic and phthioceranic acid

Abstract

A highly stereocontrolled and flexible access to biologically relevant polydeoxypropionates in optically pure form has been developed. Taking advantage of our previously established strategy for the asymmetric and stereodivergent synthesis of trideoxypropionate building blocks, we have now been able to assemble large polydeoxypropionate chains with defined configuration in a highly convergent manner. Central steps of this approach include two Suzuki-Miyaura cross-coupling reactions with subsequent highly diastereoselective hydrogenations to join three advanced synthetic intermediates in excellent yield and with full stereochemical control. We have applied this strategy successfully towards the asymmetric synthesis of glycolipid membrane components phthioceranic acid and hydroxyphthioceranic acid, the latter of which was synthesized on a half-gram scale.

Keywords: asymmetric synthesis; cross-coupling; hydrogenation; natural products; stereoselectivity.