Gist-Brocades N.v.

Shell Internationale Research Maatschappij, B.v.

Roussel Uclaf

Akzo N.v.

Shell International Petroleum Company, Ltd.

Van Zoest, Willem J.

Smid, Peter M.

Weber, Pieter G.

Marx, Arthur F.

Arthur F Marx

Gareth T Phillips

Mauro A Bertola

Hein Simon Koger

Peter D Watts

Willem J Van Zoest

Brian W Robertson

Jean Doodewaard

Peter M Smid

Jacobus N Batist

Wilhelmus J Quax

Jagdish C Kapur

Nicolaas Cornelis Barendse

Cornelis J Van Der Laken

Kenneth H Clifford

Harmen Slijkhuis

Pieter Gijsbert Weber

Jan Verwey

Cornelis Vos

Marie J De Smet

Jacobus N Batisi

Volkert P Claassen

Alison J Reid

Marie-Jose De Smet

Pieter Vellekoop

New 9-alpha-hydroxy steroids are prepared by the introduction of substituents on the D-ring of 9-alpha-hydroxy-androst-4-ene-3,17-dione. The resulting compounds are useful intermediates in the synthesis of corticosteroids.

9-alpha-hydroxy steroids, process for their preparation, process for the

9.alpha.-hydroxy-17-keto steroids are prepared by fermenting steroids having a C-17-side chain of 5-10 carbon atoms inclusive, with the novel Mycobacterium species CBS 482.86. Starting from various substrates containing a 5-10 C carbon chain on C-17, 9.alpha.-hydroxyandrost-4-ene-3,17-dione, 7.alpha.,9.alpha.,12.alpha.-trihydroxyandrost-4-ene-3,17-dione or 9.alpha.-hydroxyandrost-4,11-diene-3,17-dione is obtained in high yield. The resulting compounds are useful intermediates in the synthesis of therapeutically important steroids, particularly corticosteroids.

Preparation of 9-.alpha.-hydroxy-17-keto steroids using Mycobacterium

9.alpha.-hydroxy-17-methylene steroids, process for their preparation

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

Microbiological preparation of 9-alpha-hydroxy-17-keto steroids

The R-enantiomer of a compound of formula I: ##STR1## where Z is an optionally substituted cyclic organic moiety and C* represents an optically active carbon atom, may be prepared by supplying a substrate of formula II ##STR2## to a culture of a microorganism capable of oxidation of compound II into the R-enantiomer of I.

Certain phenoxy (or 5-trifluoromethyl-pyridyl-oxy)-phenoxy-2-yl-propane

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 for the preparation of novel 14.alpha., 17.alpha.-dihydroxy-17.beta.-substituted steroids by reacting 14.alpha.-hydroxy-17-oxo-steroids with metal organic compounds and the use of the said novel steroids in the production of 14.alpha., 17.alpha.-methylenedioxy-pregnane derivatives.

14.alpha.,17.alpha.-dihydroxy-17.beta.-substituted steroids

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 S-2-(6-methoxy-2-naphthyl)propionic acid or a pharmaceutically acceptable salt or ester thereof, which comprises supplying R-2-(6-methoxy-2-naphthyl)-propionic acid or a pharmaceutically acceptable salt or ester thereof, to a microorganism having a stereospecific inverting enzyme system, or an extract of the microorganism containing said enzyme system, capable of converting the R enantiomer to the corresponding S enantiomer.

Process for producing an optically active 2-arylpropionic acid

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

Process for the preparation of substituted phenoxy propanoic acids

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

9(11)-dehydroandrostanes and 9(11)-dehydropregnanes are prepared by dehydrating the corresponding 9-alpha-hydroxy steroid in the presence of a Lewis acid. The corresponding 8(9)-dehydro-isomer was not detectable. The resulting products are valuable intermediates in steroid synthesis especially in the preparation of corticosteroids.

Process for the preparation of 9(11)-dehydro steroids

Growing community of inventors

Delft, Netherlands

Arthur F Marx