Bristol-myers Squibb Compnay

Helmholtz-zentrum Fur Infektionsforschung Gmbh

Gerth, Klaus

Steinmetz, Heinrich

Hofle, Gerhard

Daniel A Benigni

Kenton L Shultis

Brian L Davis

Jack Z Gougoutas

Henry S Wong

John D DiMarco

Thomas P Tully

Heinrich Steinmetz

Klaus Gerth

Vittorio Farina

Shu-Jen Chiang

Paul R Brodfuehrer

Gregory L Stein

Gabriel M Galvin

Les Mintzmyer

Fahri T Comezoglu

Cary W McConlogue

Mark Mascari

Ivan Hargro

David Hou

Dennis Gu

Bruce Eagan

Hsing Hou

Robert Stankavage

The present invention relates to improved methods for the production, isolation and purification of epothilone B. These methods include, for example, a fermentation process for the production of epothilone B, isolation via adsorption onto a resin, and subsequent purification.

Methods for the preparation, isolation and purification of epothilone B, and X-ray crystal structures of epothilone B

Methods for the preparation, isolation and purification of epothilone B, and x-ray crystal structures of epothilone B

Biologically active crystalline solvates of paclitaxel are precipitated using polar, aprotic, organic solvents. A pharmaceutical composition is also disclosed, as well as the preparation of the novel solvates and their uses as anti-tumor agents.

Paclitaxel solvates

7-(Diphenylmethyl)oxy-9a-methoxymitosane is a novel intermediate for conversion into 7-amino and 7-oxy-9a-methoxymitosanes and is also useful for inhibiting mammalian tumor growth. The compound is prepared by reacting 7-hydroxy-9a-methoxymitosane with diazodiphenylmethane. In a preferred reaction, the compound is prepared from mitomycin C via 7-hydroxy-9a-methoxymitosane without drying (water removal). The intermediate is advantageously converted to the very effective anti-tumor agent 7-[2-(4-nitrophenyldithio)ethylamino]-9a-methoxymitosane in unexpectedly high yields using a two step process where the first step constitutes conversion to 7-[2-(2-pyridyldithio)ethylamino]-9a-methoxymitosane or 7-[2-(3-nitro-2-pyridyldithio)ethylamino]-9a-methoxymitosane.

Process for preparing dithio-ethylanino 9A-methoxymitosanes

7-(Diphenylmethyl)oxy-9a-methoxymitosane is a novel intermediate for conversion into 7-amino and 7-oxy-9a-methoxymitosanes and is also useful for inhibiting mammalian tumor growth. The compound is prepared by reacting 7-hydroxy-9a-methoxymitosane with diazodiphenylmethane. In a preferred reaction, the compound is prepared from mitomycin C via 7-hydroxy-9a-methoxymitosane without drying (water removal). The intermediate is advantageously converted to the very effective anti-tumor agent 7-[2-(4-nitrophenyldithio) ethylamino]-9a-methoxymitosane in unexpectedly high yields using a two step process where the first step constitutes conversion to 7-[2-(2-pyridyldithio) ethylamino]-9a-methoxymitosane. or 7-[2-(3-nitro-2-pyridyldithio)ethylamino]-9a-methoxymitosane.

Preparation of 7-(diphenylmethyl)oxy-9A-methoxymitosane

7-(diphenylmethyl)oxy-9a-methoxymitosane

A novel process utilizing adenosine deaminase to selectively produce .beta.-(D)-2',3'-dideoxyinosine in high yields from an .alpha.,.beta.-anomeric mixture. .beta.-(D)-2',3'-Dideoxyinosine so produced is useful as an antiviral and antibiotic agent.

Dideoxyinosine by enzymatic deamination of dideoxyadenosine

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Elbridge, NY, United States of America

Daniel A Benigni