Issue 47, 2019

(3S,4R)-3,4-Dihydroxy-N-alkyl-l-homoprolines: synthesis and computational mechanistic studies

Abstract

This is the first synthetic report of (3S,4R)-dihydroxy-N-alkyl-L-homoprolines described so far. 2,4-O-Benzylidene-D-erythrose was obtained from D-glucose with an improved yield, and then transformed into the title (3S,4R)-dihydroxy-N-alkyl-L-homoprolines, in a two-step strategy, with excellent overall yields. Hydrogenolysis of the benzyl group led to the NH congener. The synthesis of final products from 1,4-lactone intermediates was studied by computational means either under acidic or basic conditions. The theoretical mechanism studies fully explain the experimental results: (a) an equilibrium between L-homoprolines and their bicyclic counterparts is established in acids; (b) the equilibrium suffers a complete displacement towards the L-homoproline side in a basic medium.

Graphical abstract: (3S,4R)-3,4-Dihydroxy-N-alkyl-l-homoprolines: synthesis and computational mechanistic studies

Supplementary files

Article information

Article type
Paper
Submitted
03 Oct 2019
Accepted
05 Nov 2019
First published
08 Nov 2019

Org. Biomol. Chem., 2019,17, 10052-10064

(3S,4R)-3,4-Dihydroxy-N-alkyl-L-homoprolines: synthesis and computational mechanistic studies

D. S. Freitas, C. E. A. Sousa, J. Parente, A. Drogalin, A. Gil Fortes, N. M. F. S. A. Cerqueira and M. J. Alves, Org. Biomol. Chem., 2019, 17, 10052 DOI: 10.1039/C9OB02141H

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