Process for the production of 3-Heteroaryl-3-hydroxy-propionic acid derivatives by enantioselective microbial reduction

Producing enantiomerically enriched 3-heteroaryl-3-hydroxy-propanoic acid derivatives (I), comprises conversion of 3-heteroaryl-3-oxo-propanoic acid derivatives (II) in presence of microorganisms (or derived cell preparations) and water of pH 3-11 at 25 degreesC. Producing enantiomerically enriched 3-heteroaryl-3-hydroxy-propanoic acid derivatives of formula Het-CH(OH)-CH2-W (I), comprises conversion of 3-heteroaryl-3-oxo-propanoic acid derivatives of formula Het-CO-CH2-W (II) in presence of microorganisms (or derived cell preparations) and water of pH 3-11 at 25 degreesC. Het = 5-10 membered mono- or bicyclic aromatic group, containing 1 or 2 of N, O and/or S as heteroatom(s) (with 0-2 heteroatoms in each ring) and optionally substituted by 1-3 of OH, 1-8C alkyl, CN, COOH, COOM, COOT, OT, NT2, NHT, NO2, F, Cl, Br, 1-4C fluoroalkyl, CONH2 or CONHT; M = an equivalent of alkali(ne earth) metal; T = 1-4C alkyl; W = COOR1, CON(R1)2 or CN; R1 = H, 1-8C alkyl, 4-10C aryl or 5-11C aralkyl; and or N(R1)2 = 3-5C alkyleneimino. Independent claims are also included for: (1) preparing enantiomerically enriched 3-heteroaryl-1-amino-propan-3-ols of formula Het-CH(OH)-CH2-CH2-NR2R3 (VI), by: (a) preparing enantiomerically enriched (I) from (II) as described above; (b) subjecting the obtained (I) to the following: (i) if W = COOR1, reaction with an amine of formula NHR2R3 (III) to give an enantiomerically enriched amide of formula Het-CH(OH)-CH2-CO-NR2R3 (IV); (ii) if W = CON(R1)2, optional reaction with (III) to give (IV) having NR2R3 different from N(R1)2; or (iii) if W = CN, hydrolysis, partial hydrolysis or mixed alcoholysis/hydrolysis to give an acid, ester or amide of formula Het-CH(OH)-CH2-COR4 (V), followed by reaction with (III) if necessary to give (IV); and (c) reducing the obtained (IV) to (VI); and (2) preparing enantiomerically enriched 3-aryloxy-3-heteroaryl-1-amino-propanes of formula Het-CH(OR6)-CH2-CH2-NR2R3 (X), by preparing enantiomerically enriched (VI) as described above, then reacting with an aryl halide of formula R6-Hal. R2, R3 = H, 1-8C alkyl, 4-14C aryl or 5-15C aralkyl; or R2 + R3 = 3-12C alkylene; R4 = OR1 or NH2; R6 = phenyl or naphthyl (both optionally substituted by one or more of CN, 2-13C alkanoyl, 1-12C alkoxy, 1-12C alkyl, F, Cl, Br or 1-12C fluoroalkyl; and Hal = F, Cl, Br or I.