First Total Synthesis of 27-deoxylyngbyabellin A

In this study, we documented the first total synthesis of 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 Boc-Ile-Thz-OMe with the building block β-azido disulfide 7 to access the critical thiazole units 3 and 4, (2) chiral oxazaborolidinone-mediated asymmetry aldol reaction to construct (S)-β-hydroxy ester 5, and (3) DPPA-mediated macrolactamization of linear precursor 2 to achieve the natural product 27-deoxylyngbyabellin A.