Chemoenzymatic asymmetric synthesis of optically active pentane-1,5-diamine fragments by means of lipase-catalyzed desymmetrization transformations

A novel family of prochiral pentane-1,5-diamines has been efficiently synthesized, possessing stabilities significantly higher than those of corresponding propane-1,3-diamine analogues. Diamines have been later desymmetrized using Pseudomonas cepacia lipase as an efficient biocatalyst for the mono- but also stereoselective protection of one of their amino groups. Reaction parameters such as type and loading of enzyme, temperature, solvent, and acyl donor have been exhaustively analyzed, searching for optimal conditions for the production of interesting optically active nitrogenated compounds. Thus, acylation and alkoxycarbonylation processes have been compared in terms of conversion and enantiomeric excess values. The best results were found in the reaction of prochiral diamines with ethyl methoxyacetate as acyl donor and 1,4-dioxane as solvent, yielding (S)-monoamides in 33-59% isolated yield and 54-99% ee, depending on the aromatic pattern substitution.