Total synthesis of (+)-macbecin I

Publisher Website
Google Scholar
Abstract
The first total enantiospecific synthesis of (+)-macbecin I has been performed in a convergent manner by coupling the epoxide (3) with a higher order cyanocuprate derived from the vinyl iodide (46). The required absolute stereochemistries at C(20)–C(21) and C(12)–C(13) were accessible by enantioselective aldol condensations while that at C(16)–C(17) was achieved by Sharpless epoxidation of a secondary (E)-allylic alcohol (39), efficiently prepared by reaction of the aldehyde (37) with CrCl2-CH3CHI2. The remaining stereocentre at C-18 was introduced by an asymmetric hydroxylation of an enolate. Macrocyclization of the amino acid (59) to give the lactam (60) was successfully achieved by its reaction with either 2-mesitylenesulphonyl chloride or bis(2-oxo-3-oxazolidinyl)phosphinic chloride. Incorporation of the carbamate functionality was achieved by reaction of the parent hydroxy derivative with sodium cyanate and trifluoroacetic acid. The final oxidation to the quinone was accomplished with cerium(IV) ammonium nitrate.