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【结 构 式】 
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【分子编号】23276 【品名】5-(hydroxymethyl)-1,2,3,4-cyclohexanetetrol 【CA登记号】 |
【 分 子 式 】C6H12O6 【 分 子 量 】180.15768 【元素组成】C 40% H 6.71% O 53.28% |
合成路线1
该中间体在本合成路线中的序号：(I)By reaction of D-glucose (I) with benzaldheyde (II) by means of ZnCl2.
| 【1】 Dorcheus, S.H.; Williams, D.G.; Study of the reactions in the zinc chloride-benzal. J Org Chem 1963, 28, 775. |
| 【2】 Prous, J.; Castaner, J.; KBG. Drugs Fut 1988, 13, 9, 829. |
合成路线2
该中间体在本合成路线中的序号：(A)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 |
合成路线3
该中间体在本合成路线中的序号：(VIII)3) The reductocondensation of D-glucose (VIII) and butylamine by means of H2 over Pd/C in ethanol gives N-butylglucamine (IX), which is submitted to a biochemical oxidation by means of Gluconobacter oxidans in water to yield 6-(butylamino)-6-deoxy-a-L-sorbofuranose (X). Finally, this compound is submitted to a reductive cyclization with H2 over Pd/C in ethanol/water. 4) The selective hydrolysis of 1,2:4,6-di-O-isopropylidene-a-L-sorbofuranose (XI) (together with some of its 1,3:4,6-isomer) by means of H2SO4 in methanol gives 1,2-O-isopropylidene-a-L-sorbofuranose (XII), which is treated with tosyl chloride, triethylamine and pyridine to yield the monotosylated sugar (XIII). Reaction of the protected sugar (XIII) with butylamine in hot pyridine/triethylamine affords 6-(butylamino)-6-deoxy-1,2-O-isopropylidene-a-L-sorbofuranose (XIV), which is finally submitted to a reductive cyclization by means of H2 over Pd/C in water. 5) Directly by reductocondensation of 1-deoxynojiri-mycin (XV) with butyraldehyde (XVI) by means of H2 over Pd/C in methanol or with NaBH3CN in methanol/ HCl.
| 【1】 Sorbera, L.A.; Castaner, J.; Bayes, M.; Miglustat. Drugs Fut 2003, 28, 3, 229. |
| 【2】 Landis, B.H.; McLaughlin, J.K.; Heeren, R.; Grabner, R.W.; Wang, P.T.; Bioconversion of N-butylglucamine to 6-deoxy-6-butylamino sorbose by Gluconobacter oxydans. Org Process Res Dev 2002, 6, 4, 547. |
| 【3】 Scaros, M.G.; Prunier, M.L.; Rutter, R.J.; Yonan, P.K.; Grabner, R.; Landis, B.; A new and improved synthesis of N-butyl-1-deoxynojirimycin. Chem Ind (New York 1979) 1994, 53, 41. |
| 【4】 Junge, B.; Puls, W.; Krause, H.P.; Muller, L. (Bayer AG); New 3,4,5-Trihydroxypiperidine derivs., process for their preparation and medicaments and fodder containing them. DE 2758025; EP 0000947 . |
| 【5】 Bryant, M.L.; Koszyk, F.J.; Mueller, R.A.; Partis, R.A. (Pharmacia Corp.); Use of 1-deoxynojirimycin and its derivs. for treating mammals infected with respiratory syncytial virus. WO 9522975 . |
| 【6】 Wang, P.T.; Grabner, R.W.; Landis, B.H.; Prunier, M.L.; Scaros, M.G. (Pharmacia Corp.); Process for producing N-substd.-1-deoxynojirimycin. EP 0477160 . |
| 【7】 Partis, R.A.; Mueller, R.A.; Koszyk, F.J. (Pharmacia Corp.); Antiviral cpds.. US 5310745 . |
| 【8】 Weier, R.M.; Behling, J.R.; Farid, P.; Medich, J.R.; Khanna, I.; Prunier, M.; Scaros, M. (Pharmacia Corp.); Process for preparation of 1,5-(alkylimino)-1,5-dideoxy-D-glucitol and derivs. thereof. WO 9117145 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VIII) | 23276 | 5-(hydroxymethyl)-1,2,3,4-cyclohexanetetrol | C6H12O6 | 详情 | 详情 | |
| (IX) | 59965 | (3R,4R,5S)-6-(butylamino)-1,2,3,4,5-hexanepentol | C10H23NO5 | 详情 | 详情 | |
| (X) | 59966 | (3S,4S,5S)-5-[(butylamino)methyl]-2-(hydroxymethyl)tetrahydro-2,3,4-furantriol | C10H21NO5 | 详情 | 详情 | |
| (XI) | 59967 | C12H20O6 | 详情 | 详情 | ||
| (XII) | 59968 | (5S,7S,8S,9S)-7-(hydroxymethyl)-2,2-dimethyl-1,3,6-trioxaspiro[4.4]nonane-8,9-diol | C9H16O6 | 详情 | 详情 | |
| (XIII) | 59969 | [(5S,7S,8S,9S)-8,9-dihydroxy-2,2-dimethyl-1,3,6-trioxaspiro[4.4]non-7-yl]methyl 4-methylbenzenesulfonate | C16H22O8S | 详情 | 详情 | |
| (XIV) | 59970 | (5S,7S,8S,9S)-7-[(butylamino)methyl]-2,2-dimethyl-1,3,6-trioxaspiro[4.4]nonane-8,9-diol | C13H25NO5 | 详情 | 详情 | |
| (XV) | 17944 | deoxynojirimycin; (2R,3R,4R,5S)-2-(hydroxymethyl)-3,4,5-piperidinetriol | 19130-96-2 | C6H13NO4 | 详情 | 详情 |
| (XVI) | 23694 | butyraldehyde | 123-72-8 | C4H8O | 详情 | 详情 |