G.d. Searle & Company

Pharmacia Corporation

Monsanto Company

Pharmacia Corporation (of Pfizer, Inc.)

Searle & Co.

Ping T Wang

John S Ng

Edward E Yonan

Bernhard Erb

Yuen-Lung L Sing

Leo J Letendre

Joseph J Wieczorek

Mark John Pozzo

Chin Liu

Jon P Lawson

Dennis K Anderson

Sastry A Kunda

Julio A Baez

Gennaro Mucciariello

Fortunato Vanzanella

Bryan H Landis

Mike G Scaros

Roy W Grabner

Michael L Prunier

Richard M Weier

Thomas R Kowar

Donald W Hansen, Jr

Alan Michael Easton

Mahima Trivedi

Alok K Awasthi

Rolando E Gapud

Robert Clayton

Dean M Messing

Beverly Reitz

Mark C Walker

Suzanne L Bolten

Leslie C Engel

James Jiu

William J Marsheck

Ravindra S Topgi

The present invention relates to a novel cytochrome P450-like enzyme (11 alpha hydroxylase) and an oxidoreductase (oxidoreductase) isolated from cDNA library generated from the mRNA ofspores. When the cDNA encoding the 11 alpha hydroxylase was co-expressed in(Sf-9) insect cells with the cDNA encoding human oxidoreductase as an electron donor, it successfully catalyzed the conversion of the steroid substrate 4-androstene-3,17-dione (AD) to 11 alpha-hydroxy-AD as determined by HPLC analysis. The invention also relates to nucleic acid molecules associated with or derived from these cDNAs including complements, homologues and fragments thereof, and methods of using these nucleic acid molecules, to generate, for example, polypeptides and fragments thereof. The invention also relates to the generation of antibodies that recognizes the11 alpha hydroxylase and oxidoreductase and methods of using these antibodies to detect the presence of these native and recombinant polypeptides within unmodified and transformed host cells, respectively. The invention also provides methods of expressing the11 alpha hydroxylase gene separately, or in combination with human oroxidoreductase, in heterologous host cells, to facilitate the bioconversion of steroid substrates to their 11 alpha hydroxy-counterparts.

[object Object]

Multiple novel keto-substituted intermediates are provided for the synthesis of epoxymexrenone, useful as an Aldosterone Receptor Antagonist.

Keto-substituted steroid compounds

Intermediates in the preparation of 9,11-epoxy steroids are disclosed. Particularly, disclosed are 11,12-epoxy steroid, 4,5-9,11-diepoxy steroid and 12-keto steroid intermediates.

Processes for preparation of 9,11-epoxy steroids and intermediates useful therein

Multiple novel reaction schemes, novel process steps and novel intermediates are provided for the synthesis of epoxymexrenone and other compounds of Formula Iwherein:

Process for preparation of 9, 11-epoxy steroids and intermediates useful therein

Aspergillus ochraceus 11 alpha hydroxylase and oxidoreductase

Multiple novel reaction schemes, novel process steps and novel intermediates are provided for the synthesis of epoxymexrenone and other compounds of Formula Iwherein: &#x2014;A&#x2014;A&#x2014;, &#x2014;B&#x2014;B&#x2014;, R, R, Rand Rare as defined in the specification.

Processes for the preparation of 4,5-dihydro-5,7-lactone steroid compounds are provided.

Processes for preparation of 9, 11-epoxy steroids and intermediates useful therein

A method of separating enantiomeric lactam esters. The lactam esters are contacted with a biocatalyst, such as an enzyme or a microorganism, in a solution wherein only one enantiomer is selectively hydrolyzed to give the optically active isomer of the corresponding acid. The hydrolysis product is then separated from the unreacted lactam esters. The enzyme is then recycled for reuse in the next enzymatic resolution. The undesired isomer is also racemized and reused in the next enzymatic resolution.

Process for the enzymatic resolution of lactams

Process for preparation of 9,11-epoxy steroids and intermediates useful therein

The invention is a process for producing N-substituted glucamines, a process for oxidizing an N-substituted glucamine with an oxidizing microbe or extract thereof, and a process for oxidizing an N-substituted glucamine with an oxidizing microbe or extract thereof and reducing the oxidized N-substituted glucamine to an N-substituted-1-deoxynojirimycin. In addition, a one pot process for producing N-substituted-1-deoxynojirimycin from -glucose is disclosed.

Salt forms of 6-n-butylamino-6-deoxy-&agr;-L-sorbofuranose

A process for the formation of an epoxy compound comprising contacting a substrate compound having an olefinic double bond with a peroxide compound in the presence of a peroxide activator, said peroxide activator corresponding to the formula:

Multiple novel reaction schemes, novel process steps and novel intermediates are provided for the synthesis of epoxymexrenone, useful as a diuretic, and other compounds of Formula I

Keto-Substituted Steroid Compounds

Growing community of inventors

Ballwin, MO, United States of America

Ping T Wang