Biocatalytic processes for the preparation of stereomerically pure fused bicyclic proline compounds

A method of preparing a substantially stereomerically pure compound according to structural formula II(a):

• including salts and hydrates thereof, wherein:
• A is O, CR1R2, —C═C—, or —CH2—CH2—, wherein R1 and R2 are each independently selected from —H, COOH, —X, NH2, CH2NHC(NH)NH2, —CX3, —CH3, —CH2CH3, and wherein X is selected from F, Cl, and Br;
• M and M′ may both be present or may both be absent and when both M and M′ are present M and M′ are the same and are selected from O and CR3R4 wherein R3 and R4 are H, or R3 or R4 of M and R3 or R4 of M′ form a methylene bridge;
• with the provisos that
• (a) when M and M′ are O, A is not O;
• and when A is O, M and M′ are not O;
• (b) A can be —CH═CH— or —CH2—CH2— when M and M′ are CR3R4;
• and
• (c) when M and M′ are CR3R4 and have one or more stereocenters, the stereocenters of M and M′ are of opposite stereochemistry;
• the method comprising contacting an amine compound according to structural formula I
• wherein A, M and M′ are as defined for structural formula II(a), with oxygen in the presence of a monoamine oxidase enzyme with a cofactor under conditions in which the monoamine oxidase enzyme oxidizes the amine compound of structural formula I to a corresponding imine compound of structural formula II(a).