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

Article abstract of DOI:10.1039/c9ob02141h

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.