title: Total synthesis of everninomicin 13,384-1--Part 1: retrosynthetic analysis and synthesis of the A1B(A)C fragment.
abstract: 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: A1B(A)C fragment; 4: DE fragment; 5: FGHA2 fragment), we describe herein two approaches to the A1B(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 A1). 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-beta-phenylseleno glycosyl fluoride moiety.
authors.affiliation: Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA. kcn@scripps.edu
authors.forename: K C
authors.initials: KC
authors.lastname: Nicolaou
authors.forename: R M
authors.initials: RM
authors.lastname: Rodríguez
authors.forename: H J
authors.initials: HJ
authors.lastname: Mitchell
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: K C
authors.initials: KC
authors.lastname: Fylaktakidou
authors.forename: O
authors.initials: O
authors.lastname: Baudoin
authors.forename: F L
authors.initials: FL
authors.lastname: van Delft
mesh_terms: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D013057:Spectrum Analysis
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; C001202:evernimicin