氧氟沙星甲基化物的核磁共振波谱研究  

A Study on the NMR Spectrum of Methyl-Ofloxacin

作　　者：高秀香[1] 齐剑[1] 赵梅仙[2] 涂光中[3] 安东各[3] 徐怡庄[1] 吴瑾光[1] 

机构地区：[1]北京大学化学与分子工程学院稀土材料化学及应用国家重点实验室,北京100871 [2]北京化工大学理学院应用化学系,北京100029 [3]北京微量化学研究所,北京100091

出　　处：《光谱学与光谱分析》2008年第6期1420-1425,共6页Spectroscopy and Spectral Analysis

基　　金：国家自然科学基金项目(30371604,50673005)资助

摘　　要：结合1H NMR,13C NMR,DEPT,HSQC,HMBC谱和碳氟偶合裂分行为,对氧氟沙星(ofloxacin,OFL)哌嗪部分的甲基化产物-甲基氧氟沙星(methyl-ofloxacin,Me-OFL)的结构进行归属,并探讨了Me-OFL在酸性及碱性溶液中的1H和13C谱的变化。碱性溶液中,5H的化学位移较酸性向高场移动1.02,推测此变化与形成C—H…O弱氢键有关。6C、13C、羰基碳7C和羧基碳15C分别向低场位移12.04,7.46,4.33,2.88 ppm,推测此变化与羧基和羧酸根的转变有关。另外,还比较了OFL哌嗪环4’N上质子化产物与烷基化产物的正电荷分布。当哌嗪环质子化形成季铵盐时,正电荷分布在氢原子上;当其烷基化形成季铵盐时,正电荷分布在氮原子上。Ofloxacin （（ ± ）-9-fluoro-3-methyl-10-（4-methylpiperazin-1-yl）-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de]-1, 4-benzoxazine-6-carboxylic acid） is a totally synthetic fluoroquinolone antimicrobial agent with a broad spectrum of activity against Grampositive and Gram-negative bacteria and atypical pathogens such as Mycoplasma, Chlamydia and Legionella. Even though it is widely used for the treatment of gastrointestinal, pulmonary, urinary, and other infections, the comprehensive mechanism of action at molecular level has not been known so far. It is very important to understand the structural characteristics of the drug and the effects that are caused by the environments. With the purpose of deeply investigating the structure of Ofloxacin, an analog of Ofloxacin, Methyl-Ofloxacin （Me-OFL）, was synthesized by methylation of 4＇ N in piperazine ring from Ofloxacin with CH3 I. Then appropriate Me-OFL was dissolved in DC1/D2 O and NaOH/D2 O to prepare corresponding acidic and alkaline solutions. Systematic NMR spectroscopic investigation on Me-OFL in both acidic and alkaline solution was conducted using quantitative 1 H and 13 C spectra, DEPT, HSQC together with HMBC techniques. The spectra were recorded with Bruker AM-300 spectrometer and DRX500 spectrometer. Chemical shifts have been given in values referred to dioxane （δH = 3.7, δc = 67.8）. Complete assignments on 1 H and ^13 C signals of Me-OFL were obtained in different pH environments where the coupling constant between ^13 C and ^19F was found to be very helpful for the assignment of aromatic ^13C signals, A comprehensive comparison between the ^1 H, ^13 C chemical shifts, together with the structural transformation in acidic and alkaline solutions was made and discussed in details. Due to the formation of hydrogen bond between COOH and C=O , the COOH and aromatic ring are in the same plane. As a result, a weak O…H-C hydrogen bond forms between C=O from the carboxyl group and 5-H from aromatic ring. In alkaline solution, the deprivation of H^

关 键 词：喹诺酮 甲基氧氟沙星 核磁共振 哌嗪环 

分 类 号：O657.6[理学—分析化学]