Lenampicillin

Lenampicillin is a penicillanic acid ester that is the (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl ester of ampicillin. It is a prodrug of ampicillin. It has a role as a prodrug. It is a penicillanic acid ester and a ketene acetal. It derives from an ampicillin.

Method 1: Using 6-APA as the raw material, using methyl acetoacetate to maintain the amino group is simple, inexpensive, and has a high total yield. 10g 6-APA was suspended in 100ml dichloromethane and 10ml methanol, 9ml triethylamine and 6.5g methyl acetoacetate were added at room temperature, and then stirred at room temperature for 2h. It was concentrated under reduced pressure, and the residue was compound (I), which was directly used in the next reaction. Compound (I) was dissolved in 70ml ethyl acetate and 18ml N, N-dimethylformamide, 1.7g potassium bicarbonate, 1.2g sodium iodide and 8.2g 4-chloromethyl-5-methyl were added at 50°C Group-1, 3-dioxol-2-one, stirred at room temperature for 15h. Add 40ml of cold water and stir vigorously for 10 minutes. The organic layer was separated, washed with 5% sodium chloride aqueous solution (2×40 ml), and dried with anhydrous magnesium sulfate. The dried organic layer contains compound (II) and is directly used in the next step without purification. The solution of compound (II) obtained above was cooled to 0-5°C, and a solution of 8.7 g of p-toluenesulfonic acid monohydrate in 25 ml of ethyl acetate was added with stirring. A crystalline precipitate precipitated out within a few minutes. The suspension was stirred for 30 minutes at 5-1012. The precipitated precipitate was collected by filtration and washed with ethyl acetate to obtain 20.4g of compound (Ⅲ) with a melting point of 157-160°C (decomposition) ). The total yield of the three steps is 88%. 10g of compound (III) was suspended in 100ml of dichloromethane solution, and 2.8ml of triethylamine and 4g of ammonium bicarbonate were added under stirring at 0-5°C. Add 5g of phenylglycyl chloride in batches within 15min, and then stir at 7～10℃ for 50min. Add 70ml water and adjust to Ph7.4 with 3mol/L sodium hydroxide solution at 0～5℃. After filtration, the dichloromethane layer was separated and washed with 5% sodium chloride aqueous solution. Under 0～5℃ and stirring, add 80ml of saturated brine to the dichloromethane solution, then add 2mol/L hydrochloric acid to a Ph value of 1.5. The organic layer was separated, washed with saturated brine, and dried over anhydrous magnesium sulfate. It was concentrated under reduced pressure, and the residue was crystallized from 40 ml of 2-butanone. The crude crystals were dissolved in dichloromethane, concentrated under reduced pressure to obtain a residue, 20 ml of isopropanol and 40 ml of ethyl acetate were added, and the mixture was placed overnight at 5°C. The colorless crystals obtained by filtration were washed with cold ethyl acetate to obtain 7.6 g of lenampicillin hydrochloride with a yield of 76% and a melting point of 145°C (decomposition). Method 2: Using ampicillin as raw material. Ampicillin and benzaldehyde are dehydrated and condensed to form Schiff's base to protect the free amino group on ampicillin, and then with 4-halomethyl-5-methyl-1, 3-dioxa-4-cyclopentene-2 -Ketone (halogen = bromine or chlorine) reaction, introduce the guillotine chain on the 2 position, and finally decompose the Schiff's base acidically with methanol solution of hydrogen chloride, and remove the protective group to obtain the hydrochloride of lenmoxicillin.

Semi-synthetic penicillin is a prodrug of ampicillin, but its effect is 2 to 4 times stronger than that of ampicillin. It can be taken orally and absorbed well, with high efficiency. The use is similar to ampicillin and can be a substitute for ampicillin. For acute bronchitis, pneumonia, pulmonary suppuration, pharyngitis, trauma and surgical wounds, and other secondary infections, periodontitis, otitis media, etc.

Molecular Weight:461.5
XLogP3:1.7
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:9
Rotatable Bond Count:7
Exact Mass:461.12567125
Monoisotopic Mass:461.12567125
Topological Polar Surface Area:163
Heavy Atom Count:32
Complexity:868
Defined Atom Stereocenter Count:4
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes