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Total Synthesis of Everninomicin 13,384‐1—Part 1: Retrosynthetic Analysis and Synthesis of the A 1 B(A)C Fragment
Author(s) -
Nicolaou K. C.,
Rodríguez Rosa Maria,
Mitchell Helen J.,
Suzuki Hideo,
Fylaktakidou Konstantina C.,
Baudoin Olivier,
van Delft Floris L.
Publication year - 2000
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/1521-3765(20000901)6:17<3095::aid-chem3095>3.0.co;2-4
Subject(s) - fragment (logic) , retrosynthetic analysis , chemistry , computer science , stereochemistry , total synthesis , programming language
In this first of a series of four articles we introduce everninomicin 13,384‐1 ( 1 ), a powerful antibiotic effective against drug resistant bacteria, as a target for total synthesis and discuss its retrosynthetic analysis. From the three defined fragments required for the synthesis ( 2 : A 1 B(A)C fragment; 4 : DE fragment; 5 : FGHA 2 fragment), we describe herein two approaches to the A 1 B(A)C block. The first strategy relied on an olefin metathesis reaction to construct a common intermediate for rings B and C, but was faced with final protecting group problems. The second, and successful approach, involved a 1,2‐phenylsulfeno migration and a sulfur directed glycosidation procedure to link rings B and C, as well as an acyl fluoride intermediate to install the sterically hindered aryl ester moiety (ring A 1 ). The final stages of the synthesis of the required 2‐phenylseleno glycosyl fluoride 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‐β‐phenylseleno glycosyl fluoride moiety.