Synthesis and biophysical studies on 35-Deoxy amphotericin b methyl ester

Alex M. Szpilman; Damiano M. Cereghetti; Jeffrey M. Manthorpe; Nicholas R. Wurtz; Erick M. Carreira

doi:10.1002/chem.200900231

Synthesis and biophysical studies on 35-Deoxy amphotericin b methyl ester

Alex M. Szpilman, Damiano M. Cereghetti, Jeffrey M. Manthorpe, Nicholas R. Wurtz, Erick M. Carreira

Research output: Contribution to journal › Article › peer-review

42 Scopus citations

Abstract

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 mycosa-mine 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. 2009 Wiley-VCH Verlag GmbH & Co. KGaA.

Original language	English
Pages (from-to)	7117-7128
Number of pages	12
Journal	Chemistry - A European Journal
Volume	15
Issue number	29
DOIs	https://doi.org/10.1002/chem.200900231
State	Published - 20 Jul 2009
Externally published	Yes

Keywords

Amphotericin b
Antifungal agents
Natural products
Structure-activity relationship
Total synthesis

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10.1002/chem.200900231

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title = "Synthesis and biophysical studies on 35-Deoxy amphotericin b methyl ester",

abstract = "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 mycosa-mine 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. 2009 Wiley-VCH Verlag GmbH \& Co. KGaA.",

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AU - Cereghetti, Damiano M.

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AU - Wurtz, Nicholas R.

AU - Carreira, Erick M.

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AB - 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 mycosa-mine 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. 2009 Wiley-VCH Verlag GmbH & Co. KGaA.

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KW - Antifungal agents

KW - Natural products

KW - Structure-activity relationship

KW - Total synthesis

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Synthesis and biophysical studies on 35-Deoxy amphotericin b methyl ester

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