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Synthesis and Biophysical Studies on 35‐Deoxy Amphotericin B Methyl Ester
Author(s) -
Szpilman Alex M.,
Cereghetti Damiano M.,
Manthorpe Jeffrey M.,
Wurtz Nicholas R.,
Carreira Erick M.
Publication year - 2009
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/chem.200900231
Subject(s) - amphotericin b , aglycone , efflux , chemistry , stereochemistry , antifungal , mechanism of action , pharmacology , combinatorial chemistry , biochemistry , in vitro , biology , microbiology and biotechnology , glycoside
The use of molecular editing in the elucidation of the mechanism of action of amphotericin B is presented. A modular strategy for the synthesis of amphotericin B and its designed analogues is developed, which relies on an efficient gram‐scale synthesis of various subunits of amphotericin B. A novel method for the coupling of the mycosamine to the aglycone was identified. The implementation of the approach has enabled the preparation of 35‐deoxy amphotericin B methyl ester. Investigation of the antifungal activity and efflux‐inducing ability of this amphotericin B congener provided new clues to the role of the 35‐hydroxy group and is consistent with the involvement of double barrel ion channels in causing electrolyte efflux.