2-脱氧链霉胺取代衍生物的结构确证和~1H核磁定量  

Structure confirmation and determination of substituted 2-deoxystreptamines by proton nuclear magnetic resonance

作　　者：王海东 苏晓春 代博娜 倪瑶 李红杰 钱秀萍[3] Wang Hai-dong;Su Xiao-chun;Dai Bo-na;Ni Yao;Li Hong-jie;Qian Xiu-ping(Changzhou Fangyuan Pharmaceutical Co.,LTD.,Changzhou 213125;Instrumental Analysis Center Shanghai Jiaotong University,Shanghai 200240;School of Pharmacy Shanghai Jiaotong University,Shanghai 200240)

机构地区：[1]常州方圆制药有限公司,常州213125 [2]上海交通大学分析测试中心,上海200240 [3]上海交通大学药学院,上海200240

出　　处：《中国抗生素杂志》2019年第11期1295-1299,共5页Chinese Journal of Antibiotics

摘　　要：对新型氨基糖苷类抗生素合成中(本文阐述的是阿米卡星合成中的2个中间体,而非新型氨基糖苷类抗生素)的两个重要中间体进行结构确证和核磁定量。采用13C NMR、1H NMR、1H 1H-COSY、HMBC和MS对化合物1和化合物2进行了结构确证,并分别以马来酸和甲酸钠为内标物、D2O为溶剂,通过比较马来酸δ6.23ppm内标峰和化合物1δ5.05ppm、δ5.66ppm定量峰面积,以及甲酸钠δ8.36ppm内标峰和化合物2δ2.00ppm、δ5.72ppm定量峰面积计算化合物1和化合物2的含量。化合物1为3-氨基-3-脱氧-α-D-葡吡喃糖基-(1→6)-[2,3,4,6-四脱氧-2,6–二氨基-α-D-赤式-己吡喃糖基-(1→4)]-1-N-[(2S)-4-氨基-2-羟基-1-氧丁基]-2-脱氧-D-链霉胺,化合物2为3-氨基-3-脱氧-α-D-葡吡喃糖基-(1→6)-[2,3,4,6-四脱氧-2,6–二氨基-α-D-赤式-3-烯-己吡喃糖基-(1→4)]-1-N-[(2S)-4-氨基-2-羟基-1-氧丁基]-2-脱氧-D-链霉胺,化合物1和化合物2的含量分别为64.98%和75.38%。化合物1和化合物2是2-脱氧链霉胺取代衍生物,采用氢核磁共振内标法可快速、准确地型氨基糖苷类抗生素合成过程中无商品化标准品的重要中间体进行定量分析。The structures of two important intermediates in the synthesis of new kinds of aminoglycoside antibiotics were confirmed and the contents were determined by qNMR.The structures of the compound 1 and compound 2 were confirmed by 13C NMR,1H NMR,1H 1H-COSY,HMBC and MS.When maleic acid and sodium formate were respectively used as internal standards,and D2O was employed as solvent,the internal peak atδ6.23 for maleic acid and quantitative peaks atδ5.05 andδ5.66 for compound 1 and the internal peak atδ8.56 for sodium formate and quantitative peaks atδ2.00 andδ5.72 for compound 2 were obtained.The contents of compound 1 and compound 2 were calculated by comparing the response signal area of the sample and the internal standard.The compound 1 was 3-amino-3-deoxy-α-D-glucopyranosyl-(1→6)-[2,3,4,6-tetradeoxy-2,6-diamino]-α-D-erythrohexopyranosyl-(1→4)]-1-N-[(2S)-4-amino-2-hydroxybutanoyl]-2-deoxy-D-streptamine and compound 2 was 3-amino-3-deoxy-α-D-glucopyranosyl-(1→6)-[2,3,4,6-tetradeoxy-2,6-diamino]-α-D-erythro-hex-3-enopyranosyl-(1→4)]-1-N-[(2S)-4-amino-2-hydroxybutanoyl]-2-deoxy-D-streptamine.The contents of compound 1 and compound 2 were 64.98%and 75.38%,respectively.The two compounds were substituted 2-deoxystreptamines and the key intermediates,which standards couldn't be purchased,in the synthesis of new kinds of aminoglycoside antibiotics could be determined by qNMR rapidly and accurately.

关 键 词：2-脱氧链霉胺取代衍生物 结构确证 氢核磁共振定量 

分 类 号：R914.5[医药卫生—药物化学] R978.1[医药卫生—药学]