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DOI: 10.1055/s-0028-1087282
Synthesis of 35-Deoxy Amphotericin B Methyl Ester
Contributor(s):Philip Kocienski, Arndt W. SchmidtETH ZÜrich, Switzerland
Synthesis and Biological Studies of 35-Deoxy Amphotericin B Methyl Ester
Angew. Chem. Int. Ed. 2008, 47: 4339-4342
Publication History
Publication Date:
20 November 2008 (online)
Key words
35-deoxy amphote-ricin B methyl ester - β-glycosidation - asymmetric alkynylation - nitrile oxide cycloaddition - hexacarbonyl-molybdenum
Significance
Amphotericin B induces loss of electrochemical membrane potential by formation of ion channels. The exact mechanism of action including the necessity of the 35-hydroxy group has been debated. A scalable, modular access to the 35-deoxy derivative provides sufficient material for biological screening. Accompanying paper: E. M. Carreira and co-workers Angew. Chem. Int. Ed. 2008, 47, 4335.
Comment
A and B were synthesized from dimethyl (S)-malate and dimethyl (R)-malate, respectively. A sequence of Yamaguchi esterification followed by an intramolecular H-W-E reaction was used to form the macrolactone. Extensive optimization was required to introduce the β-mannoside and was finally achieved using the chloroisobutyrate K, which showed the right balance between electronic and steric requirements.