ABSTRACT
Asymmetric total synthesis of cyclotetradepsipeptide beauveamide A has been achieved for the first time. A macrolactamization strategy involving two possible sites has been explored to find the most effective route for cyclization. A late-stage functionalization approach has been adopted for easy access of non-natural analogues of beauveamide A for further biological evaluation. Interestingly, the anticancer activity of one of the synthesized analogues was better than that of the parent natural product.
Subject(s)
Biological Products , Biological Products/pharmacology , CyclizationABSTRACT
Asymmetric total synthesis of an acetate analogue of the endophytic unstable secondary metabolite bipolamide A has been achieved for the first time adopting a convergent approach. The key feature of this synthesis includes Evans's asymmetric ethylation, Wittig olefination, Takai olefination, stereoselective Grignard addition and intermolecular Heck coupling. This eventually developed a synthetic route of the rarely found branched amine bearing an acyloin moiety. Our synthesis finally established unambiguously the stereochemistry of the unassigned C-8 center of the naturally occurring unstable bipolamide A.