Beecham Group Plc

Beecham Group P.1.c.

Andrew W Taylor

John P Clayton

George Burton

Angela W Guest

Robert Ramage

Michael J Driver

William S MacLachlan

Richard T Cook

Richard G Adams

Compounds of the formula (I), or pharmaceutically acceptable salts thereof: ##STR1## wherein R.sub.1 is --CH.sub.2 OH; R.sub.2 is hydrogen or C.sub.1-8 alkyl; R.sub.3 is hydrogen or an amine protection group; and each R.sub.4 is hydrogen; their preparation, compositions containing them and their use in the treatment of fungal infections are described.

16-decarboxy-16-hydroxy derivatives of amphotericin B

A compound of formula (1) or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof: ##STR1## wherein R.sup.1 is phenyl, substituted phenyl or a 5- or 6-membered heterocyclic ring containing up to three heteroatoms selected from oxygen, sulphur or nitrogen, optionally substituted with hydroxy, amino, halogen or C.sub.1-6 alkoxy;

.beta.-lactam antibacterial agents and compositions containing them

A compound of formula (I) or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof: ##STR1## wherein R.sup.1 is phenyl, 4-hydroxy phenyl, 3,4-dihydroxyphenyl, 3,4-diacetoxyphenyl or a 5- or 6- membered heterocyclic ring containing up to three heteroatoms selected from oxygen, sulphur or nitrogen, optionally substituted with hydroxy, amino, halogen or C.sub.1-6 alkoxy; and R.sup.2 is a sub-group of formula (A):

Penicillins and compositions containing them

Compounds of the formula (II): ##STR1## wherein X is halogen, hydroxyl or functionalized hydroxyl; Y is halogen, hydroxyl or alkoxy; R.sup.1 is a carboxylic acid group and ester thereof and amide derivative thereof or cyano; and R.sup.2 is hydrogen, a hydrocarbon, a heterocycle, a carboxylic acid group, a carboxylic acid ester, a carboxylic acid amide derivative, acyl, cyano, isocyano or an optionally substituted imine of the formula --CH.dbd.NZ or --N.dbd.CH.sub.2 wherein Z is hydrogen, alkyl, aryl, sulphonyl, --SR.sup.a, sulphoxide --SR.sup.a, or sulphonate --SR.sup.a wherein R.sup.a is alkyl of 1 to 6 carbon atoms or aryl, are useful as intermediates for the ultimate production of penicillins or cephalosporins.

Process for preparation of thiophenes

7.alpha.-Methoxy-7.beta.-acylamino cephalosporins are prepared from 7.beta.-acylamino cephalosporins through formation of a ketenimine by the action of an acid halide, formation of an addition reaction adduct of this ketenimine, treatment of the adduct with a methoxide to form a 7.alpha.-methoxy ketenimine and hydrolysis of the latter ketenimine.

Chemical intermediates useful to prepare cephalosporins

A process for the preparation of 3-substituted thiophenes which involves cyclization of a novel intermediate, avoids the use of previously employed expensive starting materials. The thiophenes are useful for the preparation of penicillins and cephalosporins. The process is for the preparation of a thiophene of formula (I): ##STR1## where R.sup.1 represents a carboxylic acid group, or an ester or amide thereof or a nitrile group; R.sup.2 represents a group suitable for use as an .alpha.-substituent in the side-chain of a penicillin or cephalosporin; which comprises treating a compound of formula (II): ##STR2## wherein X represents halogen or optionally functionalized hydroxyl, Y represents halogen, hydroxyl, or alkoxy; with a source of nucleophilic sulphur under basic conditions.

Process for the preparation of thiophenes

Ketenimine cephalosporins

A class of ketenimine intermediates are prepared from 6-acrylaminopenicillins having an .alpha.-carboxy substituent in the side-chain, and are useful in the preparation of 6.alpha.-methoxy-.alpha.-carboxy penicillins.

Kentenimine intermediates for 6.alpha.-methoxy-.alpha.-carboxy

A class of ketenimine intermediates are prepared from 6-acylaminopenicillins having an .alpha.-carboxy substituent in the side-chain, and are useful in the preparation of 6.alpha.-methoxy-.alpha.-carboxy penicillins.

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Dorking, United Kingdom

Andrew W Taylor