First Total Synthesis of 27-Deoxylyngbyabellin A

Abstract

AbstractIn this study, we document the first total synthesis of the marine cyanobacteria secondary metabolite 27-deoxylyngbyabellin A in 10 linear steps with 9.7% overall yield. Key steps entailed (1) one-pot cascade reaction of (S)-2-(benzyloxy)-3-methylbutanoic acid and of Boc-l-Ile-OH with a β-azido disulfide building block to access two critical thiazole units, (2) chiral oxazaborolidinone-mediated asymmetric aldol reaction to construct an (S)-β-hydroxy ester, and (3) diphenyl phosphorazidate mediated macrolactamization of the assembled linear precursor to achieve the natural product 27-deoxylyngbyabellin A.