Netilmicin sulfate, Sch-20569, Certomycin, Zetamicin, Netillin, Netromicine, Netromycin, -Drug Synthesis Database

【结构式】

【药物名称】Netilmicin sulfate, Sch-20569, Certomycin, Zetamicin, Netillin, Netromicine, Netromycin

【化学名称】O-3-Deoxy-4-C-methyl-3-(methylamino)-beta-L-arabinopyranosyl-(1--6)-O-[2,6-diamino-2,3,4,6-tetradeoxy-alpha-D-glycero-hex-4-enopyranosyl-(1--4)]-2-deoxy-N1-ethyl-D-streptamine sulfate (2:5)

【CA登记号】56391-57-2, 56391-56-1 (free base)

【分子式】C₄₂H₉₂N₁₀O₃₄S₅

【分子量】1441.56814

【开发单位】Schering-Plough (Originator), Essex (Not Determined), Menarini (Licensee)

【药理作用】Antibacterial Drugs, ANTIINFECTIVE THERAPY

合成路线1 合成路线2

合成路线1

By alkylation of sisomicin (I) with acetaldehyde (II) and sodium cyanoborohydride in water with some sulfuric acid.

参考文献中间体

【1】 Castaner, J.; Loren, J.G.; Netilmicin. Drugs Fut 1978, 3, 7, 527.
【2】 Wright, J.J.; Synthesis of 1-N-ethylsisomicin: a broad-spectrum semisynthetic aminoglycoside antibiotic. J Chem Soc Chem Commun 1976, 6, 206-208.
【3】 Daniels, P.J.L.; Testa, R.; Tattanahalli, L.; Mallams, A.K.; Wright, J.J.; Weinstein, M.J.; Wagman, G.H. (Schering Corp.); Novel pseudotrisaccharides and methods for their production. DE 2437160; FR 2240015; GB 1473733; US 4029882 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	44199	(2R,3R,4R,5R)-2-[((1S,2R,3R,4S,6R)-4,6-diamino-3-[[(2S,3R)-3-amino-6-(aminomethyl)-3,4-dihydro-2H-pyran-2-yl]oxy]-2-hydroxycyclohexyl)oxy]-5-methyl-4-(methylamino)tetrahydro-2H-pyran-3,5-diol; Sisomicin	32385-11-8	C₁₉H₃₇N₅O₇	详情	详情
(II)	11974	Acetaldehyde	75-07-0	C₂H₄O	详情	详情
(III)	44200	N-((1R,2S,3R,4R,5S)-5-amino-4-[[(3R)-3-amino-6-(aminomethyl)-3,4-dihydro-2H-pyran-2-yl]oxy]-2-[[(2R,3R,4R,5R)-3,5-dihydroxy-5-methyl-4-(methylamino)tetrahydro-2H-pyran-2-yl]oxy]-3-hydroxycyclohexyl)acetamide		C₂₁H₃₉N₅O₈	详情	详情

合成路线2

The selective triacetylation of sisomicin (I) with zinc acetate, acetic anhydride and TEA in methanol/THF gives the triacetate (II), which is then alkylated with acetic acid and NaBH4 in chloroform, affording 1-N-ethyl-3,2',6'-tri-N-acetylsisomicin (III). Finally, this compound is deacetylated by means of refluxing aqueous NaOH.

参考文献中间体

【1】 Nam, G.; et al.; An efficient and selective 1-N-monoethylation of sisomicin: Process development of netilmicin. Org Process Res Dev 2002, 6, 1, 78.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	44199	(2R,3R,4R,5R)-2-[((1S,2R,3R,4S,6R)-4,6-diamino-3-[[(2S,3R)-3-amino-6-(aminomethyl)-3,4-dihydro-2H-pyran-2-yl]oxy]-2-hydroxycyclohexyl)oxy]-5-methyl-4-(methylamino)tetrahydro-2H-pyran-3,5-diol; Sisomicin	32385-11-8	C₁₉H₃₇N₅O₇	详情	详情
(II)	51894	N-([(2S,3R)-3-(acetamido)-2-[((1R,2R,3S,4R,6S)-6-(acetamido)-4-amino-3-[[(2R,3R,4R,5R)-3,5-dihydroxy-5-methyl-4-(methylamino)tetrahydro-2H-pyran-2-yl]oxy]-2-hydroxycyclohexyl)oxy]-3,4-dihydro-2H-pyran-6-yl]methyl)acetamide		C₂₅H₄₃N₅O₁₀	详情	详情
(III)	51895	N-[((2S,3R)-3-(acetamido)-2-[[(1R,2R,3S,4R,6S)-6-(acetamido)-3-[[(2R,3R,4R,5R)-3,5-dihydroxy-5-methyl-4-(methylamino)tetrahydro-2H-pyran-2-yl]oxy]-4-(ethylamino)-2-hydroxycyclohexyl]oxy]-3,4-dihydro-2H-pyran-6-yl)methyl]acetamide		C₂₇H₄₇N₅O₁₀	详情	详情

Extended Information