Methodological Advances Permit the Stereocontrolled Construction of Diverse Fully Synthetic Tetracyclines Containing an All-Carbon Quaternary Center at Position C5a.

ABSTRACT: Here we describe chemical innovations that enable the preparation of fully synthetic tetracyclines containing an all-carbon quaternary, stereogenic center at position C5a, a structurally novel class of compounds in this important family of therapeutic agents. In the key transformation and an important extension of the powerful Michael-Claisen cyclization (AB plus D) approach to the construction of fully synthetic tetracyclines, we show that the six-membered C ring comprising a C5a quaternary carbon center can be assembled by highly stereocontrolled coupling reactions of β-substituted AB enones and o-toluate ester anion D-ring precursors. Novel and versatile β-functionalization reaction sequences employing tris(methylthio)methyllithium and 2-lithio-1,3-dithiane have been developed to transf

SUBMITTER: Wright PM 

PROVIDER: S-EPMC3217274 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature