G.d. Searle & Company

Pharmacia Corporation

Monsanto Company

Pharmacia Corporation (of Pfizer, Inc.)

The Texas A&M University System

John S Ng

Ping T Wang

Chin Liu

Edward E Yonan

Bernhard Erb

Yuen-Lung L Sing

Leo J Letendre

Joseph J Wieczorek

Mark John Pozzo

Jon P Lawson

Sastry A Kunda

Dennis K Anderson

Richard A Mueller

Julio A Baez

Claire A Przybyla

Daniel P Getman

Michael L Vazquez

Fortunato Vanzanella

Gennaro Mucciariello

James R Behling

Arthur L Campbell

Kevin A Babiak

John H Dygos

Shu-Hong Zhang

Gary A DeCrescenzo

Richard M Weier

Robert M Heintz

Deborah E Bertenshaw

Scott A Laneman

Thomas R Kowar

Claire S Przybyla

John J Freskos

Suhong Zhang

Richard A Partis

Donald W Hansen, Jr

Alan Michael Easton

Mahima Trivedi

Alok K Awasthi

Rolando E Gapud

Kathleen T McLaughlin

Robert Clayton

Kalidas Paul

Beverly Reitz

Mark C Walker

Suzanne L Bolten

Leslie C Engel

Dean M Messing

Chi-Huey Wong

George W Fleet

Bryan H Landis

William J Hennen

Yi-Fong Wang

Ravindra S Topgi

Keven Anthony Babiak

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.

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A synthesis is described for intermediates which are readily amenable to the large scale preparation of hydroxyethylurea-based chiral HIV protease inhibitors. The method includes forming a diastereoselective epoxide from a chiral alpha amino aldehyde.

Method of preparing intermediates useful in synthesis of retroviral protease inhibitors

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

Chiral hydroxyethylamine, hydroxyethylurea or hydroxyethylsulfonamide isostere containing retroviral protease and renin inhibitors can be prepared by multi-step syntheses that utilize key chiral amine intermediates. This invention is a cost effective method of obtaining such key chiral amine intermediates enantiomerically, diastereomerically and chemically pure. The method is suitable for large scale (multikilogram) productions. This invention also encompasses organic acid and inorganic acid salts of the amine intermediates.

Method of preparing retroviral protease inhibitor intermediates

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

Method for preparing intermediates useful in synthesis of retroviral protease inhibitors

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

Growing community of inventors

Chicago, IL, United States of America

John S Ng