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Total synthesis of the glycosylated macrolide antibiotic fidaxomicin


Kaufmann, Elias; Hattori, Hiromu; Miyatake-Ondozabal, Hideki; Gademann, Karl (2015). Total synthesis of the glycosylated macrolide antibiotic fidaxomicin. Organic Letters, 17(14):3514-3517.

Abstract

The first enantioselective total synthesis of fidaxomicin, also known as tiacumicin B or lipiarmycin A3, is reported. This novel glycosylated macrolide antibiotic is used in the clinic for the treatment of Clostridium difficile infections. Key features of the synthesis involve a rapid and high-yielding access to the noviose, rhamnose, and orsellinic acid precursors; the first example of a β-selective noviosylation; an effective Suzuki coupling of highly functionalized substrates; and a ring-closing metathesis reaction of a noviosylated dienoate precursor. Careful selection of protecting groups allowed for a complete deprotection yielding totally synthetic fidaxomicin.

Abstract

The first enantioselective total synthesis of fidaxomicin, also known as tiacumicin B or lipiarmycin A3, is reported. This novel glycosylated macrolide antibiotic is used in the clinic for the treatment of Clostridium difficile infections. Key features of the synthesis involve a rapid and high-yielding access to the noviose, rhamnose, and orsellinic acid precursors; the first example of a β-selective noviosylation; an effective Suzuki coupling of highly functionalized substrates; and a ring-closing metathesis reaction of a noviosylated dienoate precursor. Careful selection of protecting groups allowed for a complete deprotection yielding totally synthetic fidaxomicin.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Language:English
Date:2015
Deposited On:22 Aug 2017 15:56
Last Modified:14 Feb 2018 11:34
Publisher:American Chemical Society (ACS)
ISSN:1523-7052
OA Status:Hybrid
Publisher DOI:https://doi.org/10.1021/acs.orglett.5b01602
PubMed ID:26125969

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