Bristol-myers Squibb Compnay

Li You

Paul M Skonezny

Shu-Jen Chiang

Brenda Joyce White

Akbar Nayeem

Jingyang Zhu

Thomas J Franceschini

Jonathan D Basch

Gregory L Stein

Zizhuo Xing

Wendy L Anderson

Nigel Ian Bowers

Suo-Win Liu

Yuhua Sun

John J Usher

Shannon X Zhao

Jiri Novotny

Shannon X Zha

The present invention relates to a process for preparing (2R,3S)-1-halo-2-hydroxy-3-(protected)amino-4-substituted butane comprising contacting a mutagenizedhaving ATCC deposit no. PTA-6648 with (3S)-1-halo-2-oxo-3-(protected)amino-4-substituted butane substrate. The present invention also relates to a process comprising mixing (2R,3S)-1-halo-2-hydroxy-3-(protected)amino-4-substituted butane with at least one base in the presence of at least one solvent to produce a reaction mixture containing (2R,3S)-1,2-epoxy-3-(protected)amino-4-substituted butane. The present invention further relates to a process comprising crystallizing the (2R,3S)-1,2-epoxy-3-(protected)amino-4-substituted butane out of the reaction mixture by concurrently adding water and the reaction mixture together. The present invention is also directed to a mutagenizedhaving ATCC deposit no. PTA-6648.

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Process for preparing (2R,3S)-1,2-epoxy-3-(protected)amino-4-substituted butane and intermediates thereof

Isolated nucleic acid sequences and polypeptides encoded thereby for epothilone B hydroxylase and mutants and variants thereof and a ferredoxin located downstream from the epothilone B hydroxylase gene are provided. Also provided are vectors and cells containing these vectors. In addition, methods for producing recombinant microorganisms, methods for using these recombinant microorganism to produce hydroxyalkyl-bearing epothilones and an epothilone analog produced by a mutant of epothilone B hydroxylase are provided.

Compositions and methods for hydroxylating epothilones

Provided is a method of resolving a racemic mixture of a compound of formula I to obtain a desired enantiomer:wherein Ar is Cor Caromatic group that can be substituted with H, Cto Calkyl, trifluoromethyl or halo, Ris halo or &#x2014;S&#x2014;R, wherein Ris H or acetyl, and Ris H or Cto Calkyl, the method comprising: reacting a compound of formula I wherein the compound is an ester whereby Ris Cto Calkyl with a lipase derived fromto stereoselectively hydrolyze the ester bond to produce an acid; and isolating the acid, wherein the reaction is conducted in a solvent comprising 80% to 98% v/v % organic phase and a residue of water phase (which can be buffered).

Enzymatic resolution of aryl and thio-substituted acids

New mutant penicillin G acylases preferably from are provided, exhibiting altered enzymatic activity. These penicillin G acylases are obtained by expression of a gene encoding said penicillin G acylase having an amino acid sequence which differs at least in one amino acid from the wild-type penicillin G acylase.

Mutant penicillin G acylases

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Jamesville, NY, United States of America

Li You