本文選題：沙庫必曲 + 抗心衰��； 參考：《中國醫(yī)藥工業(yè)雜志》2017年09期

【摘要】：本研究報道了一條成本低、環(huán)境友好、適合產業(yè)化的沙庫必曲半鈣鹽合成路線。以價廉易得的D-苯丙氨酸為原料,經碘代、甲酯化、氨基保護和Negishi偶聯(lián)得(R)-3-([1,1'-聯(lián)苯]-4-基)-2-[(叔丁氧羰基)氨基]丙酸甲酯,經硼氫化鋰還原、TEMPO催化氧化、縮合、氫氧化鋰水解得(R,E)-5-([1,1'-聯(lián)苯]-4-基)-4-[(叔丁氧羰基)氨基]-2-甲基-2-戊烯酸,再經鈀炭催化氫化、脫保護、乙酯化、與丁二酸酐縮合并成半鈣鹽得目標化合物。本工藝反應條件溫和,后處理操作簡便;革除了價昂或有基因毒性的試劑以及易燃易爆等危險試劑的使用。總收率22.8%,產品純度99.7%,光學純度99.8%。
[Abstract]:In this study, a low cost, environmental friendly, suitable for industrial synthesis of sarcomycinec semicalcium salt was reported. Methyl (R) -3- ([1 (1) (1) (1) (1) (1) (1) -4-phenyl] -4-yl] -2- [(tert-butyloxycarbonyl) amino] propionate was synthesized from cheap and readily available D- phenylalanine by iodination, methylation, amino protection and Negishi coupling. Methyl propionate was oxidized and condensed by lithium borohydride reductive TEMPO. Lithium-hydroxide was hydrolyzed to (RNE) -5- ([1tbutoxycarbonyl] -4-yl) -4- [(tert-butyloxycarbonyl) amino] -2-methyl-2-penteneic acid, then hydrogenated by palladium charcoal, deprotected, ethylated and condensed with succinic anhydride to form a target compound of semicalcium salt. The reaction conditions are mild, the post-treatment is simple, and the use of such dangerous reagents as combustible and explosive is removed. The total yield was 22. 8%, the purity of the product was 99. 7%, and the optical purity was 99. 8%.
【作者單位】： 浙江大學化學系;上藥集團-常州制藥廠有限公司;
【分類號】：R914

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本文編號：2086123