(3S,4R)-3,4-Dihydroxy-N-alkyl-l-homoprolines: synthesis and computational mechanistic studies
David S Freitas1, Cristina E A Sousa, Joana Parente
1Departamento de Química, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal. mja@quimica.uminho.pt.
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.
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