Bristol-myers Squibb Compnay

Bristol-myers Company

Stephen R Baker

Chester Sapino, Jr

Vittorio Farina

Gregory P Roth

Derron Ray Stark

Bang-Chi Chen

Paul M Skonezny

Sandra L Quinlan

Emerich Eisenreich

Charles Truman Holdrege

Brenda T Boyhan

An economical process, amenable to large-scale production, is disclosed for the preparation of 2',3'-didehydro-3'-deoxythymidine (d4T) from 5-methyluridine. The process employs a novel, 5'-,acyl-2'.alpha.-halo-3'.alpha.-alkanesulfonylthymidine intermediate as well as a highly efficient and practical deprotection, isolation and purification procedure for the d4T product.

Preparation of 2',3'-didehydro-3'-deoxythymidine from 5-methyluridine

An improved process suitable for large-scale production of 2',3'-didehydro-3'-deoxythymidine (d4T) and close analogs is disclosed. The improved process yields d4T in high yield and purity without the use of hazardous reactions or reagents and incorporates several process improvements important on a large scale including a novel purification step involving the isolation of a d4T.N-methylpyrrolidinone solvate.

Process for large-scale preparation of

3-Fluorosulfonyloxyceph-3-ems having a protected amino or acylamino group in the 7-position are subject to carbon-carbon bond formation at the 3-position by means of a palladium catalyzed coupling reaction with substituted organostannanes. A process for preparing cefprozil is disclosed.

3-fluorosulfonyloxyceph-3-em compounds

This invention relates to a novel process for making a cephem of formula II from 2-(3-amino-2-oxo-azetidin-1-yl)-2,3-butadienoate of formula I. In another aspect, this invention is concerned with a process of further converting a compound of formula II into an antibacterial cephem of formula III. ##STR1## In formulae I, II and III, R.sup.1 is hydrogen, a conventional amino protecting group or an acyl group; R.sup.2 is an aromatic heterocyclic or aryl group; R.sup.3 is a conventional carboxy protecting group or --CO.sub.2 R.sup.3 taken together forms a physiologically hydrolyzable ester; and R.sup.4 is a group selected from the group consisting of C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, cyclic C.sub.3-6 alkyl, and aryl; and n is 0 or 2.

Processes for making cephems from allenylazetidinone derivatives

There is disclosed a process for the production of certain 3-hydrocarbyl-3-cephem derivatives wherein the hydrocarbyl group is selected from 1-alkenyl and conjugated and unconjugated 1-polyalkenyl, 1-alkynl, carbocyclic and heterocyclic aryl, and carbocyclic and heterocyclic arylmethyl and, in the case of the 1-alkenyl and conjugated 1-polyalkenyl derivatives, with substantially complete stereospecificity, by coupling a 3-triflyloxy cephem with a hydrocarbyltributylstannane in the presence of bis(dibenzylideneacetonyl)-palladium, a phosphine, and a metal halide such as, for example, zinc chloride. The 3-unsaturated alkyl-3-cephem derivatives so-produced are useful as broad-spectrum antibacterial agents.

3-Unsaturated alkyl cephems from 3-triflyl cephems

There is disclosed a process for the production of certain 2-allyl- and 3-butenyl-3-cephem derivatives by coupling a 3-chloromethyl-3-cephem with a hydrocarbyltributystannane in the presence of bis(dibenzylideneacetonyl)-palladium and a phosphine. The 3-allyl- and 3-butenyl-3-cephem derivatives so-produced are useful as broad-spectrum antibacterial agents.

Production of 3-allyl- and 3-butenyl-3-cephems

The penicillanic acids of the formula ##STR1## wherein Z is an oxygen or sulfur atom and their pharmaceutically acceptable salts and physiologically hydrolyzed esters possess antibacterial activity and are particularly valuable in treating Pseudomonas infections.

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Cicero, NY, United States of America

Stephen R Baker