Connlab Holdings Limited

Merck + Co., Inc.

Robert B Morin

Ronald G Micetich

Edward Walton

Clinton G Chin

Burton G Christensen

Kenneth E Wilson

Burton A Christensen

An improved process for preparing 4-thia-2,6-diazabicyclo[3,2,0]hept-2-ene-7-ones such as methyl 3-phenoxy-4-thia-2,6-diazabicyclo[3,2,0]hept-2-ene-7-one-6-isopropenylacet ate which comprises extruding sulfur from dithiazeneazetidinones such as methyl 3-phenoxymethyl-4,5-dithia-2,7-diazabicyclo[4,2,0]-oct-2-ene-8-one-7-isopr openylacetate. The compounds obtained are useful intermediates in the preparation of certain 3-cephems.

Thiazoleneazetidinones from dithiazeneazetidinones

3-(.beta.-aminoethylidene)-7-oxo-4-oxaazabicyclo [3.2.0]heptane-2-carboxylic acid and derivatives thereof having the structural formula: ##STR1## and the pharmaceutically acceptable salt, ester and amide derivatives thereof are disclosed to be useful as antibiotics. Also disclosed are processes for the preparation of such compounds; pharmaceutical compositions comprising such compounds; and methods of treatment comprising administering such compounds and compositions when an antibiotic effect is indicated.

3-(.beta

3-(.beta.-aminoethylidene)-6-(.alpha.-hydroxyethyl)-7-oxo-4-oxaazabicyclo[3 .2.0]heptane-2-carboxylic acid having the structural formula: ##STR1## and the pharmaceutically acceptable salt, ester and amide derivatives thereof are disclosed to be useful as antibiotics. Also disclosed are processes for the preparation of such compounds; pharmaceutical compositions comprising such compounds; and methods of treatment comprising administering such compounds and compositions when an antibiotic effect is indicated.

3-(.beta.-Aminoethylidene)-6-(.alpha.-hyd

3-(.beta.-Hydroxyethylidene)-6-(.alpha.-Hydroxyethyl)-7-oxo-4-oxaazabicyclo [3.2.0]heptane-2-carboxylic acid having the structural formula: ##STR1## and the pharmaceutically acceptable salt, ester and amide derivatives thereof are disclosed to be useful as antibiotics. Also disclosed are processes for the preparation of such compounds; pharmaceutical compositions comprising such compounds; and methods of treatment comprising administering such compounds and compositions when an antibiotic effect is indicated.

3-(.bet

The invention relates to novel azetidinones of the general formula: ##STR1## wherein R stands for lower alkyl, phenyl, phenyloxyloweralkyl, phenylloweralkyl, 2-thiophenemethyl, 5-tetrazolylmethyl, R.sup.3 O--and R.sup.3 S--, wherein R.sup.3 stands for lower alkyl, phenyl or phenylloweralkyl; R.sup.1 is hydrogen or a cleavable radical selected from lower alkyl; loweralkoxymethyl, 2,2,2-trichloroethyl, benzyl, p-halobenzyl, p-nitrobenzyl and p-methoxybenzyl, benzhydryl and trimethylsilyl; R.sup.2 is hydrogen or methoxy; X is SCl, Sbr or --OH in which case the C.sub.3 -sidechain is better represented as the amide RCONH-- group; Y is chloro or bromo; and ##STR2## may also be taken as phthalimido. These novel compounds possess antibacterial activity and are useful intermediates for the synthesis of modified penicillins and the analogues of penicillins.

4-Chloroazetidinone-1-(2',3'-dichloroisopropyl) acetates and process for

The invention relates to compounds of the formula: ##STR1## wherein R stands for lower alkyl, aryl, heteroaryl, benzyl, heteroarylloweralkyl, phenoxyloweralkyl, phenylthioloweralkyl, 4-amino-1-butyl and suitably protected derivatives, .alpha.-aminobenzyl and protected derivatives such as the carbamates (benzyl, trichloroethyl and methoxymethyl) and aldehyde and ketone adducts, .alpha.-hydroxybenzyl and protected derivatives, .alpha.-carboxybenzyl and protected derivatives, .alpha.-sulfobenzyl and protected derivatives, the radical R.sup.5 O--, R.sup.5 S--, or R.sup.5 R.sup.6 N--,

Thioamides

The invention relates to compounds of the formula: ##STR1## wherein R stands for

Thioamides of beta-lactam antibiotics

The invention relates to compounds of the formula: ##STR1## wherein R stands for benzyl, phenoxymethyl, 4-amino-4-carboxy-1-butyl, R.sup.3 O--, R.sup.3 S--, R.sup.3 R.sup.4 N-- wherein R.sup.3 is loweralkyl, aryl or arylloweralkyl, R.sup.4 is hydrogen or R.sup.3, and OH when the radicals R.sup.3 O--, R.sup.3 S-- and R.sup.3 R.sup.4 N--are hydrolyzed; R.sup. 2 is hydrogen or methoxy, and R.sup.1 is hydrogen or a cleavable radical such as --CH.sub.2 OCH.sub.3, loweralkyl, 2,2,2-trichloroethyl, benzyl, p-nitrobenzyl, benzhydryl, phenoxyethyl or trimethylsilyl. The novel compounds are useful intermediates in the preparation of known penicillin and cephalosporin derivatives.

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Warren, NJ, United States of America

Robert B Morin