Bristol-myers Squibb Compnay

John J Usher

Guna Romancik

Michael Politino

Purushotham Vemishetti

John L Dillon, Jr

Sean M Tonzi

David A Lowe

Lee J Silverberg

Padam N Sharma

Li You

Susan D Boettger

Saibaba Racha

William V Burnett

Brenda Joyce White

Edward J Gublo

Jiri Novotny

Novel C-Calkyl- and aryl-thiotrifluoroacetates are provided which have the structure wherein Q is C-Calkyl or aryl, and are useful protecting agents for the amino or hydroxy functional groups of amines, amino acids or primary or secondary alcohols or amino alcohols to enable formation of amide bonds in peptides or proteins which are useful as screening agents, pharmaceuticals and cosmetics. A process for preparing C-Calkyl- and aryl-thiotrifluoroacetates is also provided wherein a C-Calkylthiol or arylthiol is treated with trifluoroacetic anhydride (TFAA) in the presence of organic base such as pyridine, a solvent such as dichloromethane (DCM) and dimethylaminopyridine (DMAP) as a catalyst to form the desired C-Calkyl- or aryl-thiotrifluoroacetate. In addition, a process for protecting a primary or secondary amino group or a primary or secondary hydroxyl group or an amino alcohol with a trifluoroacetyl protecting group is provided wherein a primary or secondary amine, amino acid, a primary or secondary alcohol or an amino alcohol is treated with a Cto Calkyl- or aryl-thiotrifluoroacetate in basic aqueous solution.

Alkyl and aryl-thiotrifluoroacetates and process

The present invention relates to a novel D-hydantoinase from that enantio-selectively hydrolyzes D-hydantoins to their corresponding D-N-carbamoyl-amino acids; nucleic acids that encode for the enzyme; expression vectors including the nucleic acids; and host cells capable of expressing the enzyme.

D-hydantoinase from Ochrobactrum anthropi

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

Disclosed is a process for the synthesis of .beta.-lactam antibacterials using soluble side chain esters in the presence of enzyme acylase. Also disclosed are novel esters useful as reactants in said process.

Synthesis of .beta.-lactam antibacterials using soluble side chain

Precursors of .beta.-lactam antibacterials having soluble side chain

The present invention is concerned with a chemical acetylation process for the preparation of 3'-acetylated cephalosporin from desacetyl-cephalosporin. The novel process is carried out with an acetyl donor and an activator or catalyst.

Chemical acetylation of desacetyl-cephalosporins

The instant invention provides nucleic acid molecules encoding cephalosporin esterase from Rhodosporidium toruloides. In addition, the invention provides isolated cephalosporin esterase, expression vectors, host cells, and methods of producing cephalosporin esterase.

Cephalosporin esterase gene from Rhodosporidium toruloides

Etoposide phosphate is prepared by coupling dibenzyl 4'-demethyl-4-epipodophyllotoxin-4'-phosphate with 2,3-di-O-benzyl-4,6-O-ethylidene-.alpha.,.beta.-D-glucopyranose in a solvent and subsequently removing the protecting groups. The tetra-benzyl protected etoposide phosphate is recrystallized from methanol or directly crystallized from acetonitrile by adding methanol to yield substantially the pure C-1'-.beta. form. The benzyl protecting groups are simultaneously removed by hydrogenation to produce etoposide phosphate in high yields. In a further embodiment, etoposide phosphate is treated with a phosphatase enzyme to yield etoposide.

Process of preparing etoposide phosphate and etoposide

O-acylated cephalosporins are produced by reacting 3-hydroxymethylcephalosporins with an acyl donor containing at least three carbon atoms and an enzyme which is a Rodosporidium toruloides esterase, a wheat germ lipase, an Aspergillus niger lipase, an orange peel acetylesterase or a Bacillus subtilis esterase. A preferred enzyme is the esterase from Rodosporidium toruloides ATCC 10657. The enzyme can be used while in whole cells or in soluble or inmobilized form.

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East Syracuse, NY, United States of America

John J Usher