Synthesis of the C10-C24-bis-spiroacetal core of 13-desmethyl spirolide C based on a sila-Stetter-acetalization process.

Abstract

Synthesis of the bis-spiroacetal core of 13-desmethyl spirolide C has been completed based on a sila-Stetter-acetalization process. The acylsilane and enone partners in the Stetter reaction were prepared in 7 and 11 steps, respectively, from (S) and (R)-aspartic acid. The quaternary center at C19 in the enone moiety was controlled by relying on the Seebach's chiral self-reproduction method using an enantiopure (S)-lactic acid based dioxolanone. The final acid-catalyzed spiroacetalization provided the desired spiroacetal as a mixture of diastereoisomers in 13 linear steps. Whatever the conditions used, the non-natural transoid isomer was formed preferentially. However, both cisoid and transoid isomers were isolated pure and their structure assigned unambiguously through NMR spectroscopic studies.