Work

Total Synthesis and Selective Activity of a New Class of Conformationally Restrained Epothilones

Year: 2007

Type: article

Abstract: Stereoselective total syntheses of two novel conformationally restrained epothilone analogues are described. Evans asymmetric alkylation, Brown allylation, and a diastereoselective aldol reaction served as the key steps in the stereoselective synthesis of one of the two key fragments of the convergent synthetic approach. Enzyme resolution was employed to obtain the second fragment as a single enantiomer. The molecules were assembled by esterification, followed by ring-closing metathesis. In preliminary cytotoxicity studies, one of the analogues showed strong and selective growth inhibitory activity against two leukemia cell lines over solid human tumor cell lines. The precise biological mechanism of action and high degree of selectivity of this analogue remain to be examined.

Source: Chemistry - A European Journal

DOI: 10.1002/chem.200701143

Authors: Mamoun M. Alhamadsheh, Shuchi Gupta, Richard A. Hudson, Lalith Perera, L. M. Viranga Tillekeratne

Institutions: Portland State University, University of Toledo, National Institutes of Health, National Institute of Environmental Health Sciences

Language: English

Topic: Synthetic Organic Chemistry Methods

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Institutes of Health