Gist-brocades N.v.

Shell Internationale Research Maatschappij, B.v.

Shell International Petroleum Company, Ltd.

Mauro A Bertola

Arthur F Marx

Gareth T Phillips

Hein Simon Koger

Peter D Watts

Brian W Robertson

Wilhelmus J Quax

Cornelis J Van Der Laken

Marie J De Smet

Volkert P Claassen

Marie-Jose De Smet

Process for the preparation of R-2,2-R.sub.1,R.sub.2 -1,3-dioxolane-4-methanol wherein R.sub.1 and R.sub.2 are H or alkyl groups or wherein R.sub.1 and R.sub.2 together with the carbon atom to which they are attached form a carbocyclic ring by subjecting a mixture of R- and S-2,2-R.sub.1,R.sub.2 -1,3-dioxolane-4-methanol to the action of a micro-organism or substances derived therefrom having the ability for stereoselective consumption of S-2,2-R.sub.1,R.sub.2 -1,3-dioxolane-4-methanol preferably until at least 80 wt % and more preferably all the S-2,2-R.sub.1,R.sub.2 -1,3-dioxolane-4-methanol is consumed. Various micro-organisms of the genus Rhodococcus, Nocardia and Corynebacterium are disclosed as suitable for the purpose. The R-isomer is a valuable intermediate for stereospecific synthesis of various biologically active compounds including S-metoprolol.

Process for the preparation of R-2,2-R.sub.1,R.sub.2

A process is provided for the preparation of ibuprofen enriched in R isomer, which comprises subjecting an ester of ibuprofen, to the action of a micro-organism or substances derived thereof, that will stereoselectively hydrolyse the ester to form ibuprofen predominantly having R configuration.

Process for the preparation of ibuprofen

A process is provided for the enrichment in R isomer of an aryloxypropioic acid ester and for the stereoselective hydrolysis of an aryloxypropionic acid ester to form the corresponding aryloxypropionic acid in predominantly S configuration which comprises subjecting an aryloxypropionic acid ester of formula I ##STR1## wherein A is an ester residue and preferably an alkyl group, optionally substituted or branched, wherein R' is an optionally substituted aryl or heterocyclic ring system, containing in addition to carbon atoms one or more atoms selected from nitrogen, sulphur and oxygen, this ring system being optionally substituted and wherein B and D are for example a hydrogen or a halogen atom, to the action of a microorganism or substance derived thereof capable of stereoselective hydrolysis of the COOA group to form the corresponding carboxylic acid predominantly is S configuration.

Process for the preparation of 2-aryloxypropionic acids

A process for the preparation of a pharmaceutically active compound in a stereospecific form of the formula ##STR1## or a pharmaceutically acceptable salt or ester thereof, like an alkali metal salt or an alkaline earth metal salt or a pivaloyl ester, wherein R.sub.1 represents an optionally substituted aryl group such as a phenyl or naphthyl group optionally included in a heterocyclic ring system, which is optionally substituted, or represents a heteroaromatic ring system containing in addition to carbon atoms one or more atoms selected from nitrogen, sulphur and oxygen, this ring system being optionally substituted, which comprises subjecting a compound of the formula ##STR2## wherein R.sub.2 is an ester residue and preferably an alkyl group optionally substituted, to the action of a micro-organism having the ability for stereoselective hydrolysis of compound (II) into compound (I), having at least 80% by weight the S-configuration, and if desired converting compound (I) into the pharmaceutically acceptable salt or ester thereof.

Microbial purified esterases

A process for the preparation of metoprolol in a stereospecific form or a non-toxic, pharmaceutically acceptable acid addition salt thereof and/or a stereospecific form of 4-(2-methoxyethyl)-phenyl glycidyl ether which comprises subjecting 4-(2-methoxyethyl)-phenyl allyl ether to the action of a microorganism having the ability for stereoselective epoxidation of 4-(2-methoxyethyl)-phenyl allyl ether into 4-(2-methoxyethyl)-phenyl glycidyl ether having at least 80% by weight the S configuration, at least partly separating 4-(2-methoxyethyl)-phenyl glycidyl ether and/or reacting 4-(2-methoxyethyl)-phenyl glycidyl ether with isopropylamine and at least partly separating metoprolol and/or converting metoprolol into its non-toxic, pharmaceutically acceptable acid addition salt.

Process for producing 4-(2-methoxyethyl)-phenyl-glycidyl ether and/or

A process for the preparation of a pharmaceutically active compound in a stereospecific form of the formula ##STR1## or a pharmaceutically acceptable salt or ester thereof, like an alkali metal salt or an alkaline earth metal salt or a pivaloyl ester, wherein R.sub.1 represents an optionally substituted aryl group such as a phenyl or naphthyl group optionally included in a heterocyclic ring system, which is optionally substituted, or represents a heteroaromatic ring system containing in addition to carbon atoms one or more atoms selected from nitrogen, sulphur and oxygen, this ring system being optionally substituted, which comprises subjecting a compound of the formula ##STR2## wherein R.sub.1 is an ester residue and preferably an alkyl group optionally substituted, to the action of a micro-organism having the ability for stereoselective hydrolysis of compound (II) into compound (I), having at least 80% by weight the S-configuration, and if desired converting compound (I) into the pharmaceutically acceptable salt or ester thereof.

Growing community of inventors

Delft, Netherlands

Mauro A Bertola