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

quinolone antibiotic A quinolone antibiotic is a member of 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 we ...

indicated for the treatment of urinary tract infections and certain

sexually transmitted disease Sexually transmitted infections (STIs), also referred to as sexually transmitted diseases (STDs) and the older term venereal diseases, are infections that are spread by sexual activity, especially vaginal intercourse, anal sex, and oral ...

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. Originally, the corporation was established in 1973 and merged with Synthélabo in 1999 to form Sanofi-Synthélabo. In 2004, Sanofi-Syn ...

), 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, 2 equivalents of a β-keto ester such as ethyl acetoacetate and a nitrogen donor such as ammoni ...

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, 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 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 ed., monograph 3753 On contact ...

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

References

Quinolone antibiotics 4-Pyridyl compounds Carboxylic acids {{antibiotic-stub

Synthesis

See also

References