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

• Author(s): Freitas, David S. ; Sousa, Cristina E. A. ; Parente, Joana ; Drogalim, Artem ; Fortes, A. Gil ; Cerqueira, Nuno M. F. S. A. ; Rodríguez-Borges, José E. ; Alves, Maria José Chão
• Date: 2019
• Persistent ID: https://hdl.handle.net/1822/73187
• Origin: RepositóriUM - Universidade do Minho
• Document Type: Journal article
• Language: English
• Contributor(s): Universidade do Minho

Description

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.