CHLORAMPHENICOL

Brand Name : Aquamycetin; Austracol; C.A.F.; Alficetyn: Anaphico, Anacetin: Chemicetina, Chlonycol: Chloramex; Chloramffilin; Chloramsaar; Chlorasol; Chloricol; Chlorocaps; Chlorocid; Chloromycetin; Chloronitrin; Cidocetine; Ciplamycetin; Cloramfficin; Cloramicol; Clorocyn; Cloromisan; Cylphenicol; Duphenicol; Embacetin; Enicol: Enteromycetin; Furmicetina; Fenicol; Globenicol; Interomycetine; Intramycetin; Juvamycetin; Kamaver; Kemicetine; Klorita; Leukomycin; Levomicetina; Levomycetin; Loromisin; Mastiphen; Medichol; Micloretin; Micoclorina; Microcetina; Mychel; Mycinol; Novomycetin; Opelor; Pantovernil; Paraxin; Quemicetina; Ronfenil; Stanomycetin; Synthomycetine; Tega-cetin; Tevcocin; Tifomycine; Treomicetina; Unimycetin; Veticol, Viceton; Septicol; Sintomicetino; Sno-Phenicol.

Chloramphenicol was isolated by Ehrlich and coworkers in 1947 from Streptomyces venezuelae. It was the first antimicrobial substance widely used as broad spectrum antibiotics.

It possesses two asymmetric carbon atoms in the acylamidopropanediol carbon chain giving rise to threo and erythro forms. By relating the structure to L-norephedrine.                          L-pseudonorephedrine. and D-serine it was assigned as D-(-) threo configuration.

Chloramphenicol has been synthesized by a number of routes and all the commercial material is now prepared synthetically. One of the best synthesis is from pnitroacetophenone as the starting material. Bromination of the methyl group followed by reaction with hexamine gives an amino ketone which is acetylated, hydroxy-methylated, and reduced with aluminium isopropoxide (Meerwein-Ponndort reduction). The DL-threo form so obtained predominantly was purified by crystallization. After removal of the acetyl group by hydrolysis, the threo-racemate is resolved with D camphor sulphuric acid and finally reacted with dichloroacetyl chloride.

A large number of structural analogues of chloramphenicol have been synthesized to study correlation of structure to antibiotic action. It has been found that the p-nitrophenyl group may be replaced by other aryl substituent without any loss in activity. Substitution on the phenyl ring with different nitro groups does not cause a great decrease in activity. However, the maintenance of the aromatic character of this group is essential. A conversion of the alcohol group on carbon atom of the chain to a keto group causes an appreciable loss in activity. Thus, numerous analogues have been prepared but they have all shown only similar activity or greater toxicity.

Chloramphenicol occurs as a white to greyish-white or yellswish-white, fine crystalline powder or fine crystals, needles, or elongated plates, m.p. 149-153°. It sublimes in high vacuum. It is soluble in water (1 in 400), alcohol (1 in 2.5), propylene glycol (1 in 7); freely soluble in acetone, ethyl acetate, methanol and butanol and slightly soluble in ether. It is stored in airtight containers and protected from light

Uses

Chloramphenicol is used as antibacterial in serious infections due to Haemophilus influenzae, in severe respiratory  tract infections, anaerobic infections, rickettsial infections such as typhus and Rocky Mountain spotted fever, and for a variety of eye infections due to sensitive organisms. It has also been used in skin infections. The liability of chloramphenicol to provoke life-threatening adverse effects, particularly bone-marrow aplasia, has severely limited its clinical usefulness. It should not be given for minor infections and should be discontinued immediately on the appearance of toxic symptoms. In addition to its depression of the bone marrow, haemolytic anaemia has occurred in some persons. Abnormal distension, vomiting,  hypothermia, pallid cyanosis, irregular respiration and circulatory  collapse followed by death have occurred in premature and other newborn infants receiving large doses of chloramphenicol. Hypersensitivity reactions may occur especially after topical use .