The Total Synthesis of Inostamycin A

Abstract

The first total synthesis of inostamycin A is described. With efficient and stereoselective synthetic routes to aldehyde 3 and ketone 4 developed through asymmetric aldol reactions, addition reactions and reduction, and with chiral building blocks, the two large fragments were coupled with remarkable anti stereoselectivity and efficiency by aldol condensation. The coupling reaction provided the complete carbon skeleton with all the requisite functional groups and stereogenic centers for inostamycin A. The two quaternary carbons at C20 and C16 of ketone 4 were elaborated in a highly stereocontrolled manner by addition reactions of the transmetallated 5 to ethyl ketone 6 and the transmetallated 7 to methyl ketone 8, respectively, in which the use of LaCl3 for transmetallation was critical for high coupling efficiency. The total synthesis of inostamycin A sodium salt was completed through a stereoselective and efficient aldol condensation of aldehyde A with the lithium enolate of ethyl ketone B. The two quaternary carbons at C20 and C16 of B were installed by diastereoselective addition reactions of the transmetalated species from iodides to ketones. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.