Aspoxicillin, TA-058, Doyle

阿扑西林Chemical Name: N4-Methyl-D-aspariginylamoxicillin; 6beta-[2(R)-[2(R)-Amino-4-(methylamino)-4-oxobutyramido]-2-phenylacetamido]penicillanic acid
CAS No. 63358-49-6, 63329-59-9 (stereoisomer)
项目整合开发状态: Launched-1987
项目研究机构: Merck KGaA (Originator), Tanabe Seiyaku (Originator), Esteve (Licensee), Orion Pharma (Licensee)
合成路线:The reaction of 2-amino-3-(N-methylcarbamoyl)propionic acid (I) with 2-nitrophenylsulfonylchloride (II) by means of K2CO3 in THF gives 2-(2-nitrophenylsulfonylamino)-3-(N-methylcarbamoyl)propionic acid (III),which is esterified with N-hydroxysuccinimide (IV) by means of dicyclohexylcarbodiimide in THF yielding the corresponding N-succinimido ester (V).The condensation of (V) with amoxicillin [6-[alpha-amino-alpha-(4-hydroxyphenyl)acetylamino]penicillanic acid] (VI) by means of triethylamine in THF-CHCl3 affords 6-[alpha[2-(2-nitrophenylsulfonylamino)-3-N-methylcarbamoylpropionamido]-alpha-(4-hydroxyphenyl)acetamido]penicillanic acid (VII).Finally,the sulfonic group is eliminated by treatment with thiobenzamide (A) in ethanol-THF.

合成路线:Compound (VII) can also be obtained by condensation of 6-aminopenicillanic acid (VIII) with the N-succinimido ester of alpha-[2-(2-nitrophenylsulfonylamino)-3-(N-methylcarbamoyl)propionamido]-alpha-(4-hydroxyphenyl)acetic acid (IX).Finally,the sulfonic group of (VII) is eliminated by treatment with thiobenzamide (A) in ethanol-THF.