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【结 构 式】 
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【分子编号】10776 【品名】benzyl (4aR,5aR,6S,7S,8R,9S,9aR,10aR)-6-[[(benzyloxy)carbonyl](methyl)amino]-2-[(E)-1-butenyl]-4a-hydroxy-4-oxo-7,9-bis[(trimethylsilyl)methyl]-4a,5a,6,7,8,9,9a,10a-octahydro-4H-pyrano[2,3-b][1,4]benzodioxin-8-yl(methyl)carbamate 【CA登记号】 |
【 分 子 式 】C38H50N2O9Si 【 分 子 量 】706.90858 【元素组成】C 64.57% H 7.13% N 3.96% O 20.37% Si 3.97% |
合成路线1
该中间体在本合成路线中的序号：(XVIII)Reduction of (XII) with sodium cyanoborohydride in methanolic HCl gives the 2-dimethylaminoethyl compound (XIII), which is treated with m-chloroperbenzoic acid in ethylacetate - Skellysolve B to afford the vinyl derivative (XIV). The reaction of (XIV) with ethylmagnesium bromide and CuBr2 in THF affords the protected propyl-dehydrospectinomycin (XV), which is hydrogenated with lithium tri-sec-butyl borohydride in THF to afford the propyl-spectinomycin (XVI). Finally, this compound is deprotected by hydrogenation with H2 over Pd/C in methanol. 2) The silylation of the dimethylaminovinylene compound (XII) with trimethylsilylchloride and hexamethyldisilazane in THF gives the silylated compound (XVII), which is treated with ethylmagnesium bromide to yield the 1-butenyl derivative (XVIII). The elimination of the silyl groups of (XVIII) with HF in acetonitrile affords N,N'-di(benzyloxycarbonyl)tetradehydrotrospectomycin (XIX), which is then hydrogenated with H2 over Pd/BaSO4 as before.
| 【1】 White, D.R.; Mizsak, S.A.; Birkenmeyer, R.D.; Thomas, R.C.; Wiley, V.H.; The stereospecific synthesis of spectinomycin. Tetrahedron Lett 1979, 30, 2737-40. |
| 【2】 White, D.R. (Pharmacia Corp.); 6'-Alkylspectinomycins. DE 3308196; US 4532336 . |
| 【3】 Cain, G.A.; White, D.R.; The synthesis of trospectomycin (6'-n-propylspectinomycin, U-63,366F). Tetrahedron Lett 1989, 30, 12, 1469-72. |
| 【4】 White, D.R.; Maring, C.J.; Cain, G.A.; Synthesis and in vitro antibacterial properties of alkylspectinomycin analogs. J Antibiot 1983, 36, 3, 339-42. |
| 【5】 Castaner, J.; Patoia, L.; Trospectomycin Sulfate. Drugs Fut 1991, 16, 4, 323. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XII) | 10770 | (5aR,6S,7S,8R,9S,9aR,10aR)-6,8-bis[[(benzyloxy)carbonyl](methyl)amino]-2-[(E)-2-(dimethylamino)ethenyl]-7,9-dihydroxy-4-oxo-5a,6,7,8,9,9a-hexahydro-4H-pyrano[2,3-b][1,4]benzodioxin-4(10aH)-yl acetate | C35H41N3O12 | 详情 | 详情 | |
| (XIII) | 10771 | (5aR,6S,7S,8R,9S,9aR,10aR)-6,8-bis[[(benzyloxy)carbonyl](methyl)amino]-2-[2-(dimethylamino)ethyl]-7,9-dihydroxy-4-oxo-5a,6,7,8,9,9a-hexahydro-4H-pyrano[2,3-b][1,4]benzodioxin-4(10aH)-yl acetate | C35H43N3O12 | 详情 | 详情 | |
| (XIV) | 10772 | (5aR,6S,7S,8R,9S,9aR,10aR)-6,8-bis[[(benzyloxy)carbonyl](methyl)amino]-7,9-dihydroxy-4-oxo-2-vinyl-5a,6,7,8,9,9a-hexahydro-4H-pyrano[2,3-b][1,4]benzodioxin-4(10aH)-yl acetate | C33H36N2O12 | 详情 | 详情 | |
| (XV) | 10773 | (5aR,6S,7S,8R,9S,9aR,10aR)-6,8-bis[[(benzyloxy)carbonyl](methyl)amino]-2-butyl-7,9-dihydroxy-4-oxo-5a,6,7,8,9,9a-hexahydro-4H-pyrano[2,3-b][1,4]benzodioxin-4(10aH)-yl acetate | C35H42N2O12 | 详情 | 详情 | |
| (XVI) | 10774 | benzyl (2R,4aR,5aR,6S,7S,8R,9S,9aR,10aS)-6-[[(benzyloxy)carbonyl](methyl)amino]-2-butyl-4a,7,9-trihydroxy-4-oxodecahydro-2H-pyrano[2,3-b][1,4]benzodioxin-8-yl(methyl)carbamate | C33H42N2O11 | 详情 | 详情 | |
| (XVII) | 10775 | (5aR,6S,7S,8R,9S,9aR,10aR)-6,8-bis[[(benzyloxy)carbonyl](methyl)amino]-2-[(E)-2-(dimethylamino)ethenyl]-4-oxo-7,9-bis[(trimethylsilyl)methyl]-5a,6,7,8,9,9a-hexahydro-4H-pyrano[2,3-b][1,4]benzodioxin-4(10aH)-yl acetate | C43H61N3O10Si2 | 详情 | 详情 | |
| (XVIII) | 10776 | benzyl (4aR,5aR,6S,7S,8R,9S,9aR,10aR)-6-[[(benzyloxy)carbonyl](methyl)amino]-2-[(E)-1-butenyl]-4a-hydroxy-4-oxo-7,9-bis[(trimethylsilyl)methyl]-4a,5a,6,7,8,9,9a,10a-octahydro-4H-pyrano[2,3-b][1,4]benzodioxin-8-yl(methyl)carbamate | C38H50N2O9Si | 详情 | 详情 | |
| (XIX) | 10777 | benzyl (4aR,5aR,6S,7S,8R,9S,9aR,10aR)-6-[[(benzyloxy)carbonyl](methyl)amino]-2-[(E)-1-butenyl]-4a,7,9-trihydroxy-4-oxo-4a,5a,6,7,8,9,9a,10a-octahydro-4H-pyrano[2,3-b][1,4]benzodioxin-8-yl(methyl)carbamate | C33H38N2O11 | 详情 | 详情 |