Bristol-myers Company

Bing Yu Luh

Terrence W Doyle

Bernard R Belleau

Terry T Conway

There is described the stereoselective total synthesis by a variety of routes of novel suitably substituted .DELTA..sup.2,3 -1,4-morpholine-2-carboxylic acids possessing a fused .beta.-lactam ring in the 1,6-position and carrying a substituent cis to carbon 5 in the 7-position of the fused ring system represented by the general formula ##STR1## wherein Q is hydrogen, alkyl, aralkyl or --CH.sub.2 COOZ where Z is hydrogen or the residue of an ester group and X is amino, azido or acylamino. Also included in the invention are compounds of the above formula in which the carboxyl group at the 2-position is protected as by an easily cleavable ester group and salts of both the free acids and carboxyl-protected compounds. Those compounds in which X is acylamino and their physiologically hydrolyzed esters and pharmaceutically acceptable salts are potent antibacterial agents.

.DELTA..sup.2,3 -1,4-Morpholine-2-carboxylic acid derivatives as

There is described the stereoselective total synthesis by a variety of routes of novel suitably substituted .DELTA..sup.2,3 -1, 4-morpholine-2-carboxylic acids possessing a fused .alpha.-lactam ring in the 1,6-position and carrying a substituent cis to carbon 5 in the 7-position of the fused ring system represented by the general formula ##STR1## wherein Q is hydrogen, alkyl, aralkyl or -CH.sub.2 COOZ where Z is hydrogen or the residue of an ester group and X is amino, azido or acylamino. Also included in the invention are compounds of the above formula in which the carboxyl group at the 2-position is protected as by an easily cleavable ester group and salts of both the free acids and carboxyl-protected compounds. Those compounds in which X is acylamino and their physiologically hydrolyzed esters and pharmaceutically acceptable salts are potent antibacterial agents.

O-2-Isocephem-4-carboxylic acid derivatives as antibacterial agents

There is described the stereoselective total synthesis by a variety of routes of novel suitably substituted .DELTA..sup.2,3 -1, 4-morpholine-2-carboxylic acids possessing a fused .beta.-lactam ring in the 1,6-position and carrying a substituent cis to carbon 5 in the 7-position of the fused ring system represented by the general formula ##STR1## wherein Q is hydrogen, alkyl, aralkyl or --CH.sub.2 COOZ where Z is hydrogen or the residue of an ester group and X is amino, azido or acylamino. Also included in the invention are compounds of the above formula in which the carboxyl group at the 2-position is protected as by an easily cleavable ester group and salts of both the free acids and carboxyl-protected compounds. Those compounds in which X is acylamino and their physiologically hydrolyzed esters and pharmaceutically acceptable salts are potent antibacterial agents.

There is described novel substituted .DELTA..sup.2,3 -1, 4-morpholine-2-carboxylic acids possessing a fused .beta.-lactam ring in the 1,6-position and carrying a substituent cis to carbon 5 in the 7-position of the fused ring system represented by the general formula ##STR1## wherein Q is hydrogen or alkyl and X is amino. Also included in the invention are compounds of the above formula in which the carboxyl group at the 2-position is protected as by an easily cleavable ester group and salts of both the free acids and carboxyl-protected compounds. The compounds and their physiologically hydrolyzed esters and pharmaceutically acceptable salts are useful as intermediates in the preparation of antibacterial agents.

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Brossard, Canada

Bing Yu Luh