Tanabe Seiyaku Company, Limited

Hiroaki Matsumae

Takeji Shibatani

Takuo Nishida

Yasuhiko Ozaki

Hiroyuki Akatsuka

Eri Kawai

Tadashi Kometani

Akiko Idei

Powdery aggregate of 2-phenyl-1,5-benzothiazepin-3,4(2H,5H)-dione compound: ##STR1## wherein Ring A and Ring B are benzene ring having optionally substituent selected from lower alkyl, lower alkoxy and halogen, which is prepared by admixing solution of the compound (II) in polar organic solvent with solvent which does not substantially dissolve the compound (II) but is miscible with said polar organic solvent, and separating and collecting the resultant particles of the compound (II). Said aggregate of the compound (II) can be converted into optically active 3-hydroxy-2-phenyl-2,3-dihydro-1,5-benzothiazepin-4(5H)-one compounds (I) on industrial scale, which are useful as intermediate for various medicaments.

Process for preparing optically active benzothiazepine compound and

Process for preparing optically active trans-3-phenylglycidamide compound, which comprises subjecting racemic trans-3-phenylglycidamide compound of the formula (I) ##STR1## wherein Ring A is substituted or unsubstituted benzene, and R.sup.1 is H or lower alkyl, to optical resolution using a microorganism having ability of preferentially hydrolyzing one of (2S,3R) isomer or (2R,3S) isomer thereof, and process for preparing an optically active 1,5-benzothiazepine derivative from the thus-obtained optically active trans-3-phenylglycidamide compound.

Process for preparing optically active trans-3-phenylglycidamide

A process for preparing optically active 3-phenylglycidic acid esters comprising reacting a racemic trans-3-phenylglycidic acid with an alkanol in the presence of a hydrolase to esterify preferentially either (2S, 3R) isomer or (2R, 3S) isomer of said racemic compound and isolating and collecting the resulting optically active 3-phenylglycidic acid ester from the reaction mixture, whereby the optically active ester can be produced in a single step and in a highly pure form. The optically active 3-phenylglycidic acid esters are useful for the preparation of 1,5-benzothiazepine derivatives having pharmacological activities such as platelet aggregation inhibitory activity.

Process for preparing (2S,3R)-3-alkyl-phenylglycidic acid esters using

A novel esterase which is derived from Serratia marcescens is disclosed. Said esterase has the following physico-chemical properties and enzymatic characteristics: (1) Activity; it (i.e., said esterase) hydrolyzes an ester bond of organic carboxylates, (2) Substrate specificity; it acts on alkyl esters of organic carboxylic acids, triglycerides or thiol esters, (3) Optimum pH; its optimum pH is 7.5-9.0 when the hydrolysis is carried out by using olive oil as the substrate, (4) pH stability; it is stable at pH 5.0-9.0 when it is stored at 30.degree. C. for one hour, (5) Optimum temperature; its optimum temperature is 40.degree.-50.degree. C. when the hydrolysis is carried out by using olive oil as the substrate, (6) Heat stability; it is stable at a temperature of not higher than 50.degree. C. when it is stored at pH 8.0 for 30 minutes, (7) Molecular weight; 62,000.+-.2,000 (SDS-polyacrylamide gel electrophoresis), (8) Isoelectric point; 4.6.+-.0.1, (9) Effect of metal ions; it is activated in the presence of 1 mM calcium ion, and inhibited in the presence of 1 mM cobalt ion, nickel ion, iron ion or ethylenediamine-tetraacetic acid. Said esterase can widely be applied for organic synthetic reactions.

Esterase purified from serratia marcescens SR41 (FERM BP-No. 487)

Disclosed is a process for preparing 2-halogeno-3-hydroxy-3-phenylpropionic acid ester compounds represented by the formula (I): ##STR1## wherein Ring A is a phenyl group which may be substituted, R.sup.1 is an ester residue, and X is a halogen atom, which comprises permitting an enzyme having the ability of stereoselectively reducing oxo group to hydroxy group to act on 2-halogeno-3-oxo-3-phenylpropionic acid ester compounds represented by the formula (II): ##STR2## wherein Ring A, R.sup.1 and X have the same meanings as defined above.

Growing community of inventors

Kobe, Japan

Hiroaki Matsumae