E. R. Squibb Sons, Inc.

Christopher M Cimarusti

Frederic P Hauck

Ravi K Varma

Venkatachala L Narayanan

Joseph E Sundeen

William A Slusarchyk

Rudiger D Haugwitz

Joseph E Dolfini

William H Koster

Joyce Reid

Paul Wojtkowski

Richard H Mueller

David M Floyd

Seymour D Levine

Richard B Sykes

Alan W Fritz

Frank L Weisenborn

Jerome L Moniot

Rita T Fox

William L Parker

Paul Grabowich

Donald S Karanewsky

Theodor Denzel

David R Kronenthal

Peter W Sprague

Janak Singh

Thomas P Kissick

William E Brown

Sam T Chao

Neal G Anderson

David A Lust

John Kloss

Disclosed herein are processes for preparing a compound of the formula ##STR1## in which a novel compound of the formula ##STR2## is reacted with a beta lactam of the formula ##STR3## by treatment with a base, wherein the symbols are as defined in the specification.

Process and intermediates for beta-lactams having

A process is provided for preparing (trans)-4-phenyl-DL-proline derivatives, which are useful in preparing certain angiotensin converting enzyme inhibitors, which process involves reacting an ester of the structure ##STR1## wherein X is a leaving group such as tosylate, R.sup.3 is lower alkyl, R is cyclohexyl, phenyl or substituted phenyl, and R.sup.1a is a protecting group, with a potassium amide base such as potassium hexamethyldisilazide under reduced temperatures to form the trans-4-substituted proline ester derivative of the structure ##STR2## then hydrolyzing the proline ester to the acid of the structure ##STR3## and removing the R.sup.1a nitrogen protecting group to form the unprotected acid of the structure ##STR4##

Process for preparing (trans)-4-substituted-dl-proline derivatives

A process is provided for inverting a hydroxy function of a L-trans-hydroxy proline derivative to the corresponding L-cis-hydroxy proline sulfonate by a Modified Mitsunobu reaction process.

Process for stereochemically inverting a hydroxy function of an ester by

Antibacterial activity is exhibited by .beta.-lactams having a sulfonic acid salt substituent in the 1-position and an amino or acylamino substituent in the 3-position.

2-oxo-1-azetidinesulfonic acid salts

A compund having the formula ##STR1## can be prepared by coupling a compound having the formula ##STR2## or a salt thereof, with a compound having the formula ##STR3## to yield a compound having the formula ##STR4## and oxidizing that compound to yield the desired compound; wherein R is hydrogen or an amino protecting group;

Process for the preparation of (3S)-3-[[[2-(protected

The process of this invention provides for the conversion of amino acid amides having the formula ##STR1## to 3-amino-2-oxo-1-azetidinesulfonic acid salts having the formula ##STR2## wherein one of R.sub.2 and R.sub.3 is hydrogen and the other is hydrogen, alkyl, cycloalkyl, phenyl or substituted phenyl and M.sup..sym. is hydrogen or a cation.

Process for preparing (s)-3-amino-2-oxo-1-azetidinesulfonic acid salts

A pharmaceutically acceptable salt of (R)-3-(acetylamino)-3-methoxy-2-oxo-1-azetidinesulfonic acid can be prepared by culturing Chromobacterium violaceum A.T.C.C. No. 31532 at about 25.degree. C. under submerged aerobic conditions on an aqueous nutrient medium containing an assimilable carbohydrate and nitrogen source.

Process for preparing a 2-oxo-1-azetidinesulfonic acid salt

3-Isocyanato-2-oxo-1-azetidinesulfonic acid salts are novel intermediates which are useful in processes for the preparation of 3-amino-2-oxo-1-azetidinesulfonic acid salts and 3-acylamino-2-oxo-1-azetidinesulfonic acid salts.

(S)-3-Isocyanato-2-oxo-1-azetidinesulfonic acids

Antibacterial activity is exhibited by .beta.-lactams having a phosphinic or phosphonic substituent in the 1-position and an acylamino substituent in the 3-position.

2-Oxo-1-(substituted phosphorous)azetidines

Antiinflammatory activity is exhibited by pregnenes having the structural formula ##STR1## wherein R.sub.1 is hydrogen, hydroxy, halogen, or acyloxy;

[16,17-a]Cyclopentano pregnenes

Disclosed herein is a process for preparing a compound having the formula ##STR1## which comprises coupling a compound having the formula ##STR2## or a salt thereof, with a compound having the formula ##STR3## to obtain a compound having the formula ##STR4## reacting that compound with 2-aminooxy-2-methylpropanoic acid, or a salt thereof, to obtain a compound having the formula ##STR5## and, if R is an amino protecting group, deprotecting that compound to yield the desired product; wherein

Process for preparing

Compounds having the formula ##STR1## can be prepared by reacting a compound having the formula ##STR2## with a Grignard reagent having the formula

4-Norbornyl-sulfonyl azetidinone intermediates and process for preparing

Sulfamated amino acid amides

5,6,7,8-Tetrahydronaphthalenes having the structure ##STR1## and the pharmaceutically acceptable salts thereof, are useful as blood pressure lowering agents. In the above formula R.sub.1 can be hydrogen or alkyl; R.sub.2 is alkyl; R.sub.3 and R.sub.4 can each be hydrogen, hydroxyl, alkoxy, or arylalkoxy, but both cannot be hydroxyl. Those compounds wherein at least one of R.sub.3 and R.sub.4 is other than hydrogen are novel, and constitute a part of this invention.

5,6,7,8-Tetrahydronaphthalene hypotensive agents

A process for removing the acyl sidechain from penicillins and cephalosporins which comprises chlorinating the acyl compound and treating the resulting iminochloride with an o-aminothiophenol to obtain the corresponding 6.beta.-aminopenicillin or 7.beta.-aminocephalosporin.

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Hamilton, NJ, United States of America

Christopher M Cimarusti