Synthesis of Simplified 2-Desmethyl Sanctolide A Analogs.

A one-pot, sequential phosphate tether-mediated method for the synthesis of simplified 2-desmethyl sanctolide A analogs is reported. Western side-chain diversification was achieved using a pot-efficient, sequential cross metathesis (CM)/ring-closing metathesis (RCM)/H2/dephosphorylation procedure. Further diversification was achieved by Me3Al-mediated amide formation, Yamaguchi esterification, and RCM macrocyclization to access five C11/C12 Z-configured, 2-des-methyl sanctolide A analogs with improved stability.

Total Synthesis of Sanctolide A and Formal Synthesis of (2S)-Sanctolide A.

Two synthetic strategies employing phosphate tether-mediated one-pot sequential protocols for the total synthesis of the polyketide nonribosomal peptide macrolide, sanctolide A, and the formal synthesis of the (2S)-epimer of sanctolide A are reported. In this work, a phosphate tether-mediated one-pot sequential ring-closing metathesis/cross metathesis/substrate-controlled "H2"/tether removal approach was developed to accomplish the total synthesis of the natural product sanctolide A.