A versatile and efficient synthesis of carbinolamine-containing pyrrolo[1,4]benzodiazepines via the cyclization of N-(2-aminobenzoyl)pyrrolidine-2-carboxaldehyde diethyl thioacetals: total synthesis of prothracarcin

Langley, D.R. and Thurston, D.E. (1987) A versatile and efficient synthesis of carbinolamine-containing pyrrolo[1,4]benzodiazepines via the cyclization of N-(2-aminobenzoyl)pyrrolidine-2-carboxaldehyde diethyl thioacetals: total synthesis of prothracarcin. Journal of Organic Chemistry, 52 (1). pp. 91-97. 10.1021/jo00377a016.

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DOI: 10.1021/jo00377a016

Abstract

A versatile and efficient synthesis of carbinolamine-containing pyrrolo[1,4]benzodiazepines (or the corresponding imine forms) of types 2, 7, and 8 is described that involves mercuric chloride mediated cyclization of the corresponding N-(2-aminobenzoyl)pyrrolidine-2-carboxaldehyde diethyl thioacetals. This new synthesis has significant advantages over previously existing methods in that (a) catalytic hydrogenation is not involved in the cyclization process, thus allowing preservation of unsaturation in the product, (b) all steps are mild and take place in high yields, (c) the success of the reaction is apparently independent of substituent effects, (d) the reaction proceeds with retention of stereochemistry at the aldehyde-bearing carbon, and (e) it can be readily adapted for the convergent synthesis of a variety of analogues. In addition to the synthesis of some model carbinolamine-containing compounds, the overall utility of this procedure is demonstrated by the total synthesis of prothracarcin (2d), a natural product with antitumor activity from Streptomyces umbrosus. This allowed confirmation of the E configuration previously assigned to the C2-ethylidene side chain of prothracarcin.

Item Type:Article
Departments, units and centres:Department of Pharmaceutical and Biological Chemistry > Department of Pharmaceutical and Biological Chemistry
ID Code:2944
Journal or Publication Title:Journal of Organic Chemistry
Deposited By:Library Staff
Deposited On:09 Mar 2012 14:43
Last Modified:09 Mar 2012 14:43

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