网站主页>>>项目整合精选>>>项目整合精选>>>Habekacin, Arbekacin, Habekacin

Habekacin, Arbekacin, Habekacin

阿贝卡星Chemical Name: 1-N-[(S)-4-Amino-2-hydroxybutyryl]dibekacin; 1-N-[(S)-4-Amino-2-hydroxybutyryl]-3',4'-dideoxykanamycin B; O-3-Amino-3-deoxy-alpha-D-glucopyranosyl-(1--4)-O-[2,6-diamino-2,3,4,6-tetradeoxy-alpha-D-erythro-hexopyranosyl-(1--6)]-N'-[(2S)-4-amino-2-hydroxybutyryl]-2-deoxy-L-streptamine
CAS No. 51025-85-5, 75282-65-4 (carbonate(1:2) salt)
项目整合开发状态: Launched-1990
项目研究机构: Meiji Seika (Originator)
合成路线:The acylation of 3',4'-dideoxykanamycin B (dibekacin) (I) with benzyloxycarbonyl chloride in water gives 6'-N-benzyloxycarbonyldibekacin (V),which is then acylated with (IV) as before and deprotected by hydrogenolysis with H2 over Pd/C in water - acetic acid.
📌 参考资料/链接:
参考文献标题:1-N-[(S)-alpha-hydroxy-omega-aminoacyl]
文献作者:Umezawa,H.; Umezawa,S.; Maeda,K.; Tsuchiya,O.; Kondo,S.; Fukatsu,S.(Microbial Chemistry Research Foundation)
参考来源:DE 2530169; FR 2201875; GB 1426908; JP 7462442; JP 7480039; JP 7494648; JP 7733629; JP 8003357; US 4001208; US 4107424

📄 详细内容


合成路线:The acylation of 3',4'-dideoxykanamycin B (dibekacin) (I) with N-benzyloxycarbonyloxysuccinimide (II) and zinc acetate in DMSO gives 3,2,6'-tri-N-benzyloxycarbonydibekacin (III),which is then treated with the N-hydroxysuccinimide ester of 2-hydroxy-4-aminobutyric acid (IV) and finally deprotected by hydrogenation with H2 over Pd/C in acidic water dioxane.

参考文献标题:Production of a selectively protected N-acylated derivative of an aminoglycosidic antibiotic
文献作者:Umezawa,H.; Umezawa,S.; Tsuchiya,T.; Takagi,Y.; Jikihara,T.(Microbial Chemistry Research Foundation)
参考来源:BE 0879925; DE 2945010; FR 2441631; FR 2482109; GB 2036020; GB 2065123; JP 80164696; JP 8064598; US 4297485


合成路线:The acylation of 3',4'-dideoxykanamycin B (dibekacin) (I) with tert-butyl-S-(4,6-dimethylpyrimid-2-yl)thiocarbonate (VIII) by means of triethylamine in isopropanol gives 3,2',6'-tri-N-tert-butyloxycarbonyldibekacin (IX),which is acylated again with 4-benzyloxycarbonylamino-2-hydroxybutyric acid N-hydroxysuccinimide ester (X) in THE yielding the protected habekacin (XI).Finally,this compound is deprotected by a treatment with trifluoroacetic acid,followed by hydrogenolysis with H2 over Pd/C in methanol - acetic acid.

参考文献标题:Process for the preparation of 1-N-isoseryl- or 1-N-(L-4-amino-2-hydroxybutyryl)-3',4'-dideoxykanamycin B and intermediates thereof
文献作者:Umezawa,H.; Kondo,S.(Microbial Chemistry Research Foundation)
参考来源:DE 2950020; FR 2444046; GB 2038329; GB 2072676; GB 2072677; JP 55081897; US 4268664


合成路线:The acylation of 3',4'-dideoxykanamycin B (dibekacin) (I) with N-benzyloxycarbonyloxysuccinimide (II) and zinc acetate in DMSO gives 3,2,6'-tri-N-benzyloxycarbonydibekacin (III),which is then treated with the N-hydroxysuccinimide ester of 2-hydroxy-4-aminobutyric acid (IV) and finally deprotected by hydrogenation with H2 over Pd/C in acidic water dioxane.

合成路线:The acylation of 3',4'-dideoxykanamycin B (dibekacin) (I) with benzyloxycarbonyl chloride in water gives 6'-N-benzyloxycarbonyldibekacin (V),which is then acylated with (IV) as before and deprotected by hydrogenolysis with H2 over Pd/C in water - acetic acid.

合成路线:The acylation of 3,2,6'-tri-N-benzyloxycarbonydibekacin (III) with ethyl trifluoroacetate and K2CO3 gives 3,2',6'-tri-N-benzyloxycarbonyl-3''-trifluoroacetyldibekacin (VI),which is acylated again with (IV) yielding the protected habekacin (VII).Finally,this compound is deprotected by hydrolysis with ammonia in aqueous THF,followed by hydrogenolysis with H2 over Pd/C.

合成路线:The acylation of 3',4'-dideoxykanamycin B (dibekacin) (I) with tert-butyl-S-(4,6-dimethylpyrimid-2-yl)thiocarbonate (VIII) by means of triethylamine in isopropanol gives 3,2',6'-tri-N-tert-butyloxycarbonyldibekacin (IX),which is acylated again with 4-benzyloxycarbonylamino-2-hydroxybutyric acid N-hydroxysuccinimide ester (X) in THE yielding the protected habekacin (XI).Finally,this compound is deprotected by a treatment with trifluoroacetic acid,followed by hydrogenolysis with H2 over Pd/C in methanol - acetic acid.

合成路线:The acylation of 3',4'-dideoxy-3',4'-didehydrokanamycin B (XII) with tert-butyl-S-(4,6-dimethylpyrimid-2-yl)thiocarbonate (VIII) as before gives 3,2',6'-tri-N-butoxycarbonyl-3',4'-dideoxy-3',4'-didehydrokanamycin B (XIII),which is acylated again with (X) as before yielding the fully protected 3',4'-didehydrohabekacin (XIV).Partial deprotection of (XIV) with trifluoroacetic acid affords 1-N-(4-benzyloxycarbonylamino-2-hydroxybutyryl)-3',4'-dideoxy-3',4'-didehydrokanamycin B (XV),which is finally debenzylated and reduced by a treatment with H2 over PtO2 in aqueous acetic acid.

参考文献标题:Habekacin
文献作者:Serradell,M.N.; Castar,J.; Blancafort,P.
参考来源:Drugs Fut 1983,8(5),410


合成路线:The acylation of 3,2,6'-tri-N-benzyloxycarbonydibekacin (III) with ethyl trifluoroacetate and K2CO3 gives 3,2',6'-tri-N-benzyloxycarbonyl-3''-trifluoroacetyldibekacin (VI),which is acylated again with (IV) yielding the protected habekacin (VII).Finally,this compound is deprotected by hydrolysis with ammonia in aqueous THF,followed by hydrogenolysis with H2 over Pd/C.
参考文献标题:1-N-Acylation of aminocyclitol antibiotics via zinc chelation and regiospecific N-trifluoroacetylation
文献作者:Tsuchiya,T.; Takagi,Y.; Umezawa,S.
参考来源:Tetrahedron Lett 1979,(51),4951-54


产品链接: CAS No. 51025-85-5››