Kagemoto A, Negoro T, Nakao M, Ochi T, Chiba K, Kataoka M, Sekine Y
Research Laboratory, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan.
Arzneimittelforschung. 1991 Jul;41(7):744-6.
A new antimicrobial quinolone, sparfloxacin (5-amino-1-cyclopropyl-7- (cis-3,5-dimethyl-1-piperazinyl)-6,8-difluoro-1,4-dihydro-4-oxoquinoline -3- carboxylic acid, AT-4140; CAS 110871-86-8), was labeled by 14C for studies of disposition and metabolism. Ethyl pentafluoro[carbonyl-14C]benzoylacetate (I) was reacted with ethyl orthoformate, cyclopropylamine and then potassium tert-butoxide to give a quinolone intermediate (IV). A benzylamino derivative (V) obtained by condensation of IV and benzylamine was subject to catalytic hydrogenolysis and hydrolyzed to give the carboxyl derivative (VII), which was condensed with cis-2,6-dimethylpiperazine to form [carbonyl-14C]sparfloxacin. The average yield of 3 preparations was 41.5% and specific activities were 310.8-366.3 MBq (8.4-9.9 mCi)/mmol. Both chemical and radiochemical purities were greater than 99%.
一种新型抗菌喹诺酮类药物司帕沙星（5-氨基-1-环丙基-7-（顺式-3,5-二甲基-1-哌嗪基）-6,8-二氟-1,4-二氢-4-氧代喹啉-3-羧酸，AT-4140；化学物质登记号110871-86-8），用¹⁴C进行标记，用于处置和代谢研究。五氟[羰基-¹⁴C]苯甲酰乙酸乙酯（I）与原甲酸乙酯、环丙胺反应，然后与叔丁醇钾反应，得到喹诺酮中间体（IV）。IV与苄胺缩合得到的苄氨基衍生物（V）经催化氢解和水解，得到羧基衍生物（VII），VII与顺式-2,6-二甲基哌嗪缩合形成[羰基-¹⁴C]司帕沙星。3次制备的平均产率为41.5%，比活度为310.8 - 366.3 MBq（8.4 - 9.9 mCi）/mmol。化学纯度和放射化学纯度均大于99%。
