A new efficient synthesis of enantiopure diastereomeric 3 '-aminocyclopentylglycines

A new synthesis of enantiopure (1′S,3′R,2R)- and (1′R,3′S,2R)-3′-aminocyclopentylglycines (-)-12a and (-)-12b was performed by taking advantage of (±)-2-amino-3-oxo-norbornane-2-carboxylic acid derivative exo-2 as the starting material. The use of an acylase from Aspergillus melleus in phosphate buffer allowed the 'one-pot' transformation of the β-ketoester (±)-exo-2 into 3′-carboxycyclopentylglycine (±)-3a and (±)-3b, via a retro-Dieckman reaction, which, by direct kinetic resolution, were isolated as compounds (-)-3a and (-)-3b. Starting from a mixture of (-)-3a and (-)-3b, enantiopure 3′-aminocyclopentylglycines (-)-12a and (-)-12b as well as differently substituted 3-amino derivatives were prepared efficiently using a very simple synthetic protocol that requires a single chromatographic purification.