Total synthesis of erythromycin B

Philippe Breton, Paul J. Hergenrother, Tsuneaki Hida, Anne Hodgson, Andrew S. Judd, Erica Kraynack, Philip R. Kym, Wen Cherng Lee, Michael S. Loft, Masayuki Yamashita, Stephen F. Martin

Research output: Contribution to journalArticlepeer-review

Abstract

We report the details of the first total synthesis of erythromycin B using two different strategies for the end game. The first of these follows a classical approach in which the desosamine and cladinose residues are sequentially appended to a macrocyclic lactone, which was formed by cyclization of a seco acid derivative, to give a bis-glycosylated macrolide intermediate that is converted into erythromycin B. The second strategy features an abiotic approach in which a seco acid bearing a desosamine residue is cyclized to give a monoglycosylated macrocyclic lactone that is then transformed into erythromycin B via a sequence of steps involving refunctionalizations and a glycosylation to introduce the cladinose moiety. Attempts to prepare a bis-glycosylated seco acid by de novo synthesis were unsuccessful. The syntheses of the key seco acid intermediates feature the oxidative transformation of a furan containing C(3)-C(10) to provide a dioxabicyclo[3.3.1]nonenone that served as a template on which to create the stereocenters at C(6) and C(8). A stereoselective aldol reaction was used to establish the C(11)-C(15) segment, and a stereoselective crotylation was implemented to introduce the propionate subunit comprising C(1)-C(2).

Original languageEnglish (US)
Pages (from-to)5709-5729
Number of pages21
JournalTetrahedron
Volume63
Issue number26
DOIs
StatePublished - Jun 25 2007
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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