|
【结 构 式】 
|
【分子编号】13055 【品名】(2R,4aR,6S,7R,8R,8aS)-7,8-Bis(benzyloxy)-2-methylhexahydropyrano[3,2-d][1,3]dioxin-6-ol 【CA登记号】 |
【 分 子 式 】C22H26O6 【 分 子 量 】386.44484 【元素组成】C 68.38% H 6.78% O 24.84% |
合成路线1
该中间体在本合成路线中的序号：(II)The condensation of dibenzyl-sugar (II) with 4'-demethyl-epipodophyllotoxin (I) by means of BF3·Et2O in acetonitrile gives a mixture of the alpha and beta coupled products (IV) + (III), which by crystallization in dichloromethane/methanol afforded pure diastereomer beta (III). Finally this compound is debenzylated by hydrogenolysis with H2 over Pd/C in THF.
| 【1】 Silverberg, L.J.; et al.; A crystallization-induced steroselective glycosidation reaction in the synthesis of the anticancer drug etoposide. Org Lett 2000, 2, 21, 3281. |
| 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) | 13053 | (5R,5aR,8aR,9S)-9-Hydroxy-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,8,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6(5aH)-one | 6559-91-7 | C21H20O8 | 详情 | 详情 |
| (II) | 13055 | (2R,4aR,6S,7R,8R,8aS)-7,8-Bis(benzyloxy)-2-methylhexahydropyrano[3,2-d][1,3]dioxin-6-ol | C22H26O6 | 详情 | 详情 | |
| (III) | 41886 | (5R,5aR,8aR,9S)-9-[[(2R,4aR,6R,7R,8R,8aS)-7,8-bis(benzyloxy)-2-methylhexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy]-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,8,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6(5aH)-one | C43H44O13 | 详情 | 详情 | |
| (IV) | 41891 | (5R,5aR,8aR,9S)-9-[[(2R,4aR,6S,7R,8R,8aS)-7,8-bis(benzyloxy)-2-methylhexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy]-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,8,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6(5aH)-one | C43H44O13 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(III)A new synthesis for etoposide phosphate disodium salt has been reported: The reaction of 4'-demethylepipodophpyllotoxin (I) with dibenzyl phosphite and diisopropylethylamine (DIEA) in acetonitrile gives the corresponding 4'-dibenzyl phosphate ester (II), which is condensed with 2,3-di-O-benzyl-4,6-O-ethylidene-alpha,beta-D-glucose (alpha:beta ratio = 85:15) by means of boron trifluoride ethearate in acetonitrile to afford the tetrabenzylated compound (IV). Finally, this compound is deprotected by hydrogenolysis with H2 over Pd/C in methanol/THF.
| 【1】 Silverberg, L.J.; Vemishetti, P.; Dillon, J.L. Jr.; Usher, J.J. (Bristol-Myers Squibb Co.); Process of preparing etoposide phosphate and etoposide. EP 0652226; JP 1995196680; JP 1998152499; US 5459248 . |
| 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) | 13053 | (5R,5aR,8aR,9S)-9-Hydroxy-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,8,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6(5aH)-one | 6559-91-7 | C21H20O8 | 详情 | 详情 |
| (II) | 13050 | 4-[(5R,5aR,8aR,9S)-9-hydroxy-6-oxo-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl]-2,6-dimethoxyphenyl dibenzyl phosphate | C35H33O11P | 详情 | 详情 | |
| (III) | 13055 | (2R,4aR,6S,7R,8R,8aS)-7,8-Bis(benzyloxy)-2-methylhexahydropyrano[3,2-d][1,3]dioxin-6-ol | C22H26O6 | 详情 | 详情 | |
| (IV) | 13056 | 4-((5R,5aR,8aR,9S)-9-[[(2R,4aR,6R,7R,8R,8aS)-7,8-bis(benzyloxy)-2-methylhexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy]-6-oxo-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl)-2,6-dimethoxyphenyl dibenzyl phosphate | C57H57O16P | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(III)The reaction of D-glucopyranose (A) with allyl alcohol (B) by means of HCl gives glucoside (C), which is treated with acetaldehyde diethylacetal (D) and TsOH in dichloromethane to yield the 4,6-O-ethylideneglucoside (E). Reaction of (E) with benzyl bromide (F), by means of NaH in DMF, affords the 2,3-di-O-benzyl-4,6-O-ethylideneglucoside (G), which is treated with potassium tert-butoxide and with HgO, HgCl2 to give the fully protected sugar (III).
| 【1】 Vemishetti, P.; Sleezer, P.D.; Dillon, J.L.; Discordia, R.P.; Hartung, K.B.; Silverberg, L.J.; Efficient synthesis of the anticancer drug etoposide 4'-phosphate: Use of benzylic ether-protecting groups on the carbohydrate segment. Org Process Res Dev 2000, 4, 1, 34. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (B) | 12234 | 2-Propen-1-ol; Allyl alcohol | 107-18-6 | C3H6O | 详情 | 详情 |
| (F) | 12912 | 1-(Bromomethyl)benzene; Alpha-bromotoluene | 100-39-0 | C7H7Br | 详情 | 详情 |
| (A) | 23276 | 5-(hydroxymethyl)-1,2,3,4-cyclohexanetetrol | C6H12O6 | 详情 | 详情 | |
| (E) | 40484 | (2R,4aR,7R,8R,8aS)-6-(allyloxy)-2-methylhexahydropyrano[3,2-d][1,3]dioxine-7,8-diol | C11H18O6 | 详情 | 详情 | |
| (G) | 40485 | (2R,4aR,7R,8R,8aS)-6-(allyloxy)-7,8-bis(benzyloxy)-2-methylhexahydropyrano[3,2-d][1,3]dioxine; (2R,4aR,7R,8R,8aS)-6-(allyloxy)-7-(benzyloxy)-2-methylhexahydropyrano[3,2-d][1,3]dioxin-8-yl benzyl ether | C25H30O6 | 详情 | 详情 | |
| (D) | 40486 | 1-ethoxyethyl ethyl ether; 1,1-diethoxyethane | 105-57-7 | C6H14O2 | 详情 | 详情 |
| (III) | 13055 | (2R,4aR,6S,7R,8R,8aS)-7,8-Bis(benzyloxy)-2-methylhexahydropyrano[3,2-d][1,3]dioxin-6-ol | C22H26O6 | 详情 | 详情 | |
| (C) | 40483 | (3R,4S,5S,6R)-2-(allyloxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol | C9H16O6 | 详情 | 详情 |