Rosoxacin (also known as acrosoxacin, tradename Eradacil) is a

quinolone antibiotic Quinolone antibiotics constitute a large group of broad-spectrum bacteriocidals that share a bicyclic core structure related to the substance 4-quinolone. They are used in human and veterinary medicine to treat bacterial infections, as wel ...

indicated for the treatment of urinary tract infections and certain

sexually transmitted disease A sexually transmitted infection (STI), also referred to as a sexually transmitted disease (STD) and the older term venereal disease (VD), is an infection that is spread by sexual activity, especially vaginal intercourse, anal sex, or ...

s. Rosoxacin is not available in the United States. It was developed in 1978 by George Lesher and his colleagues at Winthrop-Stearns (now part of

sanofi-aventis Sanofi S.A. is a French multinational pharmaceutical and healthcare company headquartered in Paris, France. The corporation was established in 1973 and merged with Synthélabo in 1999 to form Sanofi-Synthélabo. In 2004, Sanofi-Synthélabo merg ...

), as an extension of the work that originally led to

nalidixic acid Nalidixic acid (tradenames Nevigramon, NegGram, Wintomylon and WIN 18,320) is the first of the synthetic quinolone antibiotics. In a technical sense, it is a naphthyridone, not a quinolone: its ring structure is a 1,8-naphthyridine nucleus that ...

. It is classified as a first generation quinolone.

Synthesis

The synthesis of rosoxacin begins with a modified

Hantzsch pyridine synthesis The Hantzsch pyridine synthesis or Hantzsch dihydropyridine synthesis is a multi-component organic reaction between an aldehyde such as formaldehyde Formaldehyde ( , ) (systematic name methanal) is an organic compound with the chemical for ...

employing as component parts

ammonium acetate Ammonium acetate, also known as spirit of Mindererus in aqueous solution, is a chemical compound with the formula NH4CH3CO2. It is a white, hygroscopic solid and can be derived from the reaction of ammonia and acetic acid. It is available commerci ...

, two equivalents of

methyl propiolate Methyl propiolate is an organic compound with the formula HC2CO2CH3. It is the methyl ester of propiolic acid, the simplest acetylenic carboxylic acid. It is a colorless liquid that is miscible with organic solvents. The compound is a reagent a ...

, and one of 3-nitrobenzaldehyde. Oxidation of the resulting dihydropyridine (2) with nitric acid followed by saponification, decarboxylation, and reduction of the nitro group with iron and HCl acid gives aniline 3. This undergoes the classic sequence of Gould-Jacobs reaction with methoxymethylenemalonate ester to form the 4-hydroxyquinoline ring, and then alkylation with

ethyl iodide Ethyl iodide (also iodoethane) is a transparency and translucency, colorless flammable chemical compound. It has the chemical formula C2H5I and is prepared by heating ethanol with iodine and phosphorus.''Merck Index of Chemicals and Drugs'', 9th e ...

and saponification of the ester to complete the synthesis of the antibacterial agent rosoxacin (4).

References

{{QuinoloneAntiBiotics Quinolone antibiotics 4-Pyridyl compounds Carboxylic acids

Synthesis

See also

References