The Upjohn Co.

Joseph M Timko

Kyoung S Kim

Michael R Barbachyn

Ronald B Gammill

Thomas M Judge

Sharon N Bisaha

Verlan H Van Rheenen

A quinolone compound of Formula (I) ##STR1## as defined herein having antibacteria properties, pharmaceutical compositions containing the quinoline compound and method for treating bacterial infections in animals including humans.

Antibacterial quinolone compounds

The process of the present invention transforms 16.alpha.- or 16.beta.-methyl-17-keto steroids (I) to the corresponding 17.alpha.-ethynyl-17.beta.-hydroxy-16.alpha.- or 16.beta.-methyl steroids (II) without epimerization and loss of stereochemistry of the 16.alpha.- or 16.beta.-methyl group.

Ethynylation of 16-methyl-17-keto steroids

3-(Activated ester)methyl-3-cephem-4-carboxylic acids are prepared by the direct reaction of a 3-hydroxymethyl-3-cephem-4-carboxylic acid with an activated-O-ester-methyl forming acylating agent in the presence of a 4-(tertiary amino)pyridine catalyst, and an acid absorbing base, in a non-polar liquid solvent at -78.degree. C. to +30.degree. C.

Catalytic process for preparing 3-ester-methyl cephalosporins from

.DELTA..sup.4 -3-keto, .DELTA..sup.1,4 -3-keto and 3.beta.-hydroxy 17-keto steroids (I) are transformed into the corresponding 16-.beta.-methyl-17-keto steroids (IV) by first activating the C-16 position, then methylating. By protecting the C-3 position of the .DELTA..sup.4 -3-keto and 3.beta.-hydroxy steroids the yields are greatly increased.

16.beta.-Methyl steroid process

Perchloryl fluoride when reacted with the appropriately protected 9.alpha.-hydroxyandrostenedione stereoselectively produces the corresponding 6.beta.-fluoro steroid.

Introduction of a fluorine atom

Spironolactone (VIII) is produced from ethisterone (I) by formation of the lactone (IV), a halo lactone (VI) and a .DELTA.4,6-lactone (VII).

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Kalamazoo, MI, United States of America

Joseph M Timko