Cefpodoxime proxetil

Cefpodoxime Proxetil is a first oral and broad spectrum antibiotic that belongs to the third generation of cephalosporin. Cefpodoxime Proxetil binds to penicillin binding proteins (PBPs), which inhibits peptidoglycan synthesis, finally results in interfering bacterial cell wall biosynthesis[1].

Preparation of Side Chain 280 ml of ethyl chloroformate and 260 ml of sulfuryl chloride were mixed, and 1.0 g of benzoyl peroxide was added at room temperature. After refluxing for 7.5h, distillation yielded 217g of 1-chloroethyl chloroformate (boiling point 119-140°C. Dissolve 317g of this ester in 2000ml of dichloromethane, add 397g of isopropanol under cooling and stirring. Add dropwise within 20min 230ml of pyridine, and stirring for 30min after addition. The reaction solution was washed with 500ml of water, 500ml of brine and 5% aqueous potassium hydrogen sulfate solution, and dried over anhydrous magnesium sulfate. After the solvent was distilled off, it was distilled under reduced pressure to obtain 228g of 1-chloroethyl iso Propyl carbonate, boiling point 92-94°C/7.33MPa. 102g of this carbonate is dissolved in 1000ml of benzene, 200g of sodium iodide and 5g of 18-crown-6 are added and refluxed overnight. The reaction solution is water and 5% sodium thiosulfate After washing, the organic layer was dried over anhydrous magnesium sulfate. It was concentrated under reduced pressure to obtain 144 g of the desired side chain, namely 1-iodoethyl isopropyl carbonate. 7-ACA was acylated to obtain compound (I). 26 g of compound (I ) And 4.1g of sodium bicarbonate dissolved in 80ml of water, at room temperature were added 1.70ml of methanol and 375g of calcium dichloride dihydrate, and then stirred at 70 ℃ for 75min. The reaction solution was poured into 500ml of ice water, using 10ml of concentrated hydrochloric acid Acidified, then extracted with ethyl acetate (2×500m1). The extracts were combined, washed with brine, and then extracted with 10% potassium monohydrogen phosphate aqueous solution (sequentially 350, 150, and 100m1). The water-soluble extracts were combined and used After acidifying with hydrochloric acid, it was extracted with ethyl acetate (2×500m1). The ethyl acetate extract was washed with brine, dried over anhydrous magnesium sulfate, and a precipitate appeared when it was concentrated to 1/5 volume. It was left at room temperature for 3h, and the precipitate was collected by filtration. 15.97g of compound (II) was obtained with a yield of 64.8%. 8g of compound (II) and 4g of sodium bicarbonate were dissolved in 20ml of water, 1.82g of thiourea was added at room temperature. After stirring at room temperature for 14h, the resulting precipitate was filtered to remove Under ice-cooling and stirring, 20 ml of concentrated hydrochloric acid was added. The resulting precipitate was filtered again. The filtrate was adjusted to Ph=2~3 with an aqueous solution of sodium hydroxide. The resulting precipitate was collected by filtration to obtain 5.12 g of compound (III), yield 75.5 %. 427 mg of compound (III) was dissolved in 20 ml of N, N-dimethylacetamide (DMA), and under cooling, 200 mg of dicyclohexylamine and 310 mg of 1-iodoethylisopropyl carbonate were added in sequence. After stirring for 30 min , Add 100 ml of ethyl acetate. Remove the resulting precipitate by filtration, and the filtrate was washed successively with dilute hydrochloric acid, aqueous sodium bicarbonate, and brine. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow solid. The solid was subjected to silica gel column chromatography , Ethyl acetate-cyclohexane (3: 1) elution, to obtain 50lmg cefpodoxime ester, yield 89.9%.

An antibacterial. A broad spectrum, orally absorbed third generation cephalosporin, ester prodrug of the active free acid metabolite, Cefpodoxime

Molecular Weight:557.6
XLogP3:0.6
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:14
Rotatable Bond Count:13
Exact Mass:557.12501980
Monoisotopic Mass:557.12501980
Topological Polar Surface Area:235
Heavy Atom Count:37
Complexity:976
Undefined Atom Stereocenter Count:3
Undefined Bond Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes