Chemistry:Cefmenoxime

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

Synthesis

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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]

References

  1. ↑ "Cefmenoxime. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use". Drugs 34 (2): 188–221. August 1987. doi:10.2165/00003495-198734020-00002. PMID 3304966. 
  2. ↑ Ochiai M, Okada T, Aki O, Morimoto A, Kawakita K, Matsushita Y, "Thiazolylacetamido cephalosporin type compounds", US patent 4098888, issued 7 April 1978
  3. ↑ "New cephalosporin derivatives with high antibacterial activities". Chemical & Pharmaceutical Bulletin 25 (11): 3115–3117. November 1977. doi:10.1248/cpb.25.3115. PMID 603968. 
  4. ↑ "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. doi:10.7164/antibiotics.34.171. PMID 6271716. 
  5. ↑ "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. doi:10.7164/antibiotics.34.186. PMID 6271717. 

Further reading

  • "[Antibacterial activities of cefmenoxime against recent fresh clinical isolates from patients in sinusitis]". The Japanese Journal of Antibiotics 48 (5): 602–609. May 1995. PMID 7637194. 
  • "Pharmacoeconomic analysis of cefmenoxime dual individualization in the treatment of nosocomial pneumonia". The Annals of Pharmacotherapy 28 (3): 384–389. March 1994. doi:10.1177/106002809402800316. PMID 8193431. 
  • "Cefmenoxime in corneal organ culture". Ophthalmologica 208 (5): 262–266. 1994. doi:10.1159/000310505. PMID 7816419. 




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