Total synthesis of erythromycin B

Autor: Andrew S. Judd, Tsuneaki Hida, Philippe Breton, Stephen F. Martin, Philip R. Kym, Masayuki Yamashita, Erica Kraynack, Paul J. Hergenrother, W.‐C. Lee, Michael S. Loft, Anne V. Hodgson
Rok vydání: 2007
Předmět:
Zdroj: Tetrahedron. 63:5709-5729
ISSN: 0040-4020
DOI: 10.1016/j.tet.2007.02.044
Popis: 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).
Databáze: OpenAIRE
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