I The tandem chain extension-acylation reaction II Synthesis of papyracillic acid A: Application of the tandem homologation-acylation reaction III Synthesis of tetrahydrofuran-based peptidomimetics

Abstract

A zinc-mediated tandem chain extension-acylation reaction was successfully developed. This reaction was optimized with the use of beta-keto esters, amides, and imides as well as a variety of acylating agents. The tandem homologation-acylation reaction was successfully applied towards the total synthesis of papyracillic acid A. Use of a tandem chain extension-aldol reaction, followed by a reductive cyclization, allowed for the synthesis of tetrahydrofuran-based peptidomimetics. A variety of amino acid derived beta-keto imides and aldehydes were used during the initial tandem homologation-aldol reaction. High diastereocontrol was achieved during reductive cyclization when a cis relationship was present between the substituents on the tetrahydrofuran ring. Use of beta-keto imides during the chain extension reaction was important as they led to the formation of the required anti-aldol products