Process for preparing 2-halogeno-3-hydroxy-3-phenyl-propionic acid ester compounds

A process for preparing an optically active benzothiazepine compound represented by the formula (IV):

• ##STR13## wherein Rings A and B are phenyl groups which may be substituted, comprising the steps of:
• permitting an enzyme having the ability of enantioselectively reducing an oxo group to a hydroxy group to act on a 2-chloro-3-oxo-3-phenylpropionic acid ester compound represented by the formula (II):
• ##STR14## wherein Ring A has the same meaning as defined above and R.sup.1 is an ester residue, so as to form an optically active 2-chloro-3-hydroxy-3-phenylpropionic acid ester compound represented by the formula (I):
• ##STR15## subjecting said compound of formula (I) to intramolecular ring closure to form an optically active compound of formula (III):
• ##STR16## and reacting said compound of formula (III) with a compound of the formula ##STR17## under appropriate conditions to form the benzothiazepine compound of formula IV.

A process for preparing a benzothiazepine compound represented by the formula (IV-1) ##STR18## wherein Ring A is a phenyl group which may be substituted, comprising the steps of:

• permitting an enzyme having the activity of enantioselectively reducing an oxo group to a hydroxy group of the absolute configuration of S, to act on a 2-chloro-3-oxo-3-phenylpropionic acid ester compound represented by the formula ##STR19## wherein R.sup.1 is an ester residue, so as to form an optically active (2R, 3S)-type and/or (2S, 3S)-type 2-chloro-3-hydroxy-3-phenylpropionic acid ester compound represented by the formula (I-1):
• ##STR20## subjecting said compound of formula (I-1) to intramolecular ring closure to form an optically active trans-(2R, 3S) compound of formula (III-1):
• ##STR21## reacting said compound of formula (III-1) with a compound of the formula:
• ##STR22## under appropriate conditions to form the benzothiazepine compound of formula (IV-1).

A process for preparing a benzothiazepine compound represented by the formula (IV-2):

• ##STR23## wherein Ring A and Ring B each is a phenyl group which may be substituted, comprising the steps of:
• permitting an enzyme having the activity of enantioselectively reducing an oxo group to a hydroxy group of the absolute configuration of R, to act on a 2-chloro-3-oxo-3-phenylpropionic acid ester compound represented by the formula (II):
• ##STR24## wherein R.sup.1 is an ester residue, so as to form an optically active (2R,3R)-type and/or (2S, 3R)-type 2-chloro-3-hydroxy-3-phenylpropionic acid ester compound represented by the formula (I-2):
• ##STR25## subjecting said compound of formula (I-2) to intramolecular ring closure to form an optically active trans(2R,3S) compound of formula (III-2):
• ##STR26## reacting said compound of formula (III-2) with a compound of the formula:
• ##STR27## under appropriate conditions to form the benzothiazepine compound of formula (IV-2).

A process for preparing trans-3-phenylglycidates represented by the formula (III):

• ##STR28## wherein Ring A is a phenyl group which may be substituted and R.sup.1 is an ester residue,
• which comprises permitting an enzyme having the ability of enantioselectively reducing an oxo group to a hydroxy group to act on a 2-chloro-3-oxo-3-phenylpropionic acid ester compound represented by the formula (II):
• ##STR29## wherein Ring A and R.sup.1 are the same meanings as defined above, to give a 2-chloro-3-hydroxy-3-phenylpropionic acid ester compound represented by the formula (I):
• ##STR30## wherein Ring A and R.sup.1 are the same meanings as defined above, and subjecting the thus-obtained compound (I) to an intramolecular ring closure reaction.