Cefmenoxime Explained

Cefmenoxime is a third-generation cephalosporin antibiotic.^[1]

Synthesis

The alkylation of ethyl 2-hydroxyimino-3-oxobutanoate (1) with dimethylsulfate gives ethyl (2Z)-2-methoxyimino-3-oxo-butanoate (2). Halogenation with molecular bromine leads to ethyl 4-bromo-2-methoxyimino-3-oxobutanoate (3). Treatment with thiourea gives ethyl (Z)-2-(2-amino-4-thiazolyl)-2-methoxyiminoacetate (4) which is reacted with chloroacetyl chloride to give the amide (5). Saponification with potassium hydroxide gives (6) which is halogenated with phosphorus pentachloride to (7). Amide formation with the cephalosporin intermediate (8) then gives (9). Removal of the protecting group with benzyltriethylammonium bromide yields (10). The tert-butyl ester was deprotected with trifluoroacetic acid to give (11). Lastly, thioether formation with 5-mercapto-1-methyltetrazole (12) completes the synthesis of cefmenoxime.^{[2] [3] [4] [5]}

Further reading

• Yokota N, Koguchi M, Suzuki Y, Fukayama S, Ishihara R, Deguchi K, Oda S, Tanaka S, Nakane Y, Fukumoto T . [Antibacterial activities of cefmenoxime against recent fresh clinical isolates from patients in sinusitis] . The Japanese Journal of Antibiotics . 48 . 5 . 602–609 . May 1995 . 7637194 .
• Paladino JA, Fell RE . Pharmacoeconomic analysis of cefmenoxime dual individualization in the treatment of nosocomial pneumonia . The Annals of Pharmacotherapy . 28 . 3 . 384–389 . March 1994 . 8193431 . 10.1177/106002809402800316 . 29444681 .
• Duncker GI, Reich U, Krausse R . Cefmenoxime in corneal organ culture . Ophthalmologica. Journal International d'Ophtalmologie. International Journal of Ophthalmology. Zeitschrift Fur Augenheilkunde . 208 . 5 . 262–266 . 1994 . 7816419 . 10.1159/000310505 .

Notes and References

1. Campoli-Richards DM, Todd PA . Cefmenoxime. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use . Drugs . 34 . 2 . 188–221 . August 1987 . 3304966 . 10.2165/00003495-198734020-00002 .
2. Ochiai M, Okada T, Aki O, Morimoto A, Kawakita K, Matsushita Y . Thiazolylacetamido cephalosporin type compounds . US . 4098888 . 7 April 1978 . Takeda Pharmaceutical Co Ltd. .
3. Ochiai M, Aki O, Morimoto A, Okada T, Matsushita Y . New cephalosporin derivatives with high antibacterial activities . Chemical & Pharmaceutical Bulletin . 25 . 11 . 3115–3117 . November 1977 . 603968 . 10.1248/cpb.25.3115 . free .
4. Ochiai M, Morimoto A, Miyawaki T, Matsushita Y, Okada T, Natsugari H, Kida M . Synthesis and structure-activity relationships of 7 beta-[2-(2-aminothiazol-4-yl)acetamido]cephalosporin derivatives. V. Synthesis and antibacterial activity of 7 beta-[2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-cephalosporin derivates and related compounds . The Journal of Antibiotics . 34 . 2 . 171–185 . February 1981 . 6271716 . 10.7164/antibiotics.34.171 . free .
5. Ochiai M, Morimoto A, Miyawaki T . Synthesis and structure-activity relationships of 7 beta-[2-(2-aminothiazol-4-yl)acetamido]cephalosporin derivatives. VI. Alternative syntheses of 7 beta-[2-(2-aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido]cephalosporin derivatives . The Journal of Antibiotics . 34 . 2 . 186–192 . February 1981 . 6271717 . 10.7164/antibiotics.34.186 . free .