Total synthesis of everninomicin 13,384-1 - Part 1: Retrosynthetic analysis and synthesis of the A(1)B(A)C fragment

In this first of a series of four articles we introduce everninomicin 13,38 4-1 (1), a powerful antibiotic effective against drug resistant bacteria, a s a target for total synthesis and discuss its retrosynthetic analysis, Fro m the three defined fragments required for the synthesis (2: A(1)B(A)C frag ment; 3: DE fragment: 5: FGHA(2) fragment), we describe herein two approach es to the A(1)B(A)C block. The first strategy relied on an olefin metathesi s reaction to construct a common intermediate for rings B and C, but was fa ced with final protecting group problems. The second, and successful approa ch, involved a 1,2-phenplsulfeno migration and a sulfur directed glycosidat ion procedure to link rings B and C, as well as an acyl fluoride intermedia te to install the sterically hindered aryl ester moiety (ringA(1)). The fin al stages of the synthesis of the required 2--phenylseleno glycosyl fluorid e 2 required introduction of a phenylseleno group at C-1 of ring C followed by a novel, DAST-promoted 1,2-migration to produce the desired 2-beta-phen ylseleno glycosyl fluoride moiety.