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【结 构 式】 
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【分子编号】38071 【品名】[(7S)-4,4-diphenyl-3,5-dioxabicyclo[5.1.0]oct-1-yl]methanol 【CA登记号】 |
【 分 子 式 】C19H20O3 【 分 子 量 】296.366 【元素组成】C 77% H 6.8% O 16.2% |
合成路线1
该中间体在本合成路线中的序号：(VI)The reaction of diethyl malonate (I) with (R)-(-)-epichlorohydrin (II) by means of sodium ethoxide in refluxing ethanol gives the 3-oxa-2-oxobicyclic compound (III), which by reduction with NaBH4 in ethanol yields (1S,2R)-1,2-bis(hydroxymethyl)cyclopropanecarboxylic acid ethyl ester (IV). The reaction of (IV) with diphenyldiazomethane by means of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) in dichloroethane affords (1R,7R)-4,4-diphenyl-3,5-dioxabicyclo[5.1.0]octane-1-carboxylic acid ethyl ester (V), which is reduced with LiBH4 in THF giving the carbinol (VI). The reaction of (VI) with CBr4 and triphenylphosphine in dichloromethane yields the bromomethyl derivative (VII), which is condensed with 5-(2-(E)-bromovinyluracil (VIII) by means of K2CO3 and 18-crown-6 in hot DMF affording the expected addition compound (IX). Finally, this compound is deprotected with HCl in methanol.
| 【1】 Onishi, T.; Mukai, C.; Sekiyama, T.; Tsuji, T.; Iwayama, S.; Okunishi, M. (Ajinomoto Co., Inc.); Bis(hydroxymethyl)cyclopropylmethyl pyrimidine derivs.,their preparation and their use as anti-viral agents. EP 0649840; JP 1995165731; US 5496824 . |
| 【2】 Onishi, T.; Mukai, C.; Nakagawa, R.; et al.; Synthesis and antiviral activity of novel anti-VZV 5-substituted uracil nucleosides with a cyclopropane sugar moiety. J Med Chem 2000, 43, 2, 278. |
| 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) | 16829 | Diethyl malonate | 105-53-3 | C7H12O4 | 详情 | 详情 |
| (II) | 38067 | (2R)-2-(Chloromethyl)oxirane; (R)-Epichlorohydrin | 51594-55-9 | C3H5ClO | 详情 | 详情 |
| (III) | 38068 | ethyl (1S,5R)-2-oxo-3-oxabicyclo[3.1.0]hexane-1-carboxylate | C8H10O4 | 详情 | 详情 | |
| (IV) | 38069 | ethyl (1R,2R)-1,2-bis(hydroxymethyl)cyclopropanecarboxylate | C8H14O4 | 详情 | 详情 | |
| (V) | 38070 | ethyl (1R,7S)-4,4-diphenyl-3,5-dioxabicyclo[5.1.0]octane-1-carboxylate | C21H22O4 | 详情 | 详情 | |
| (VI) | 38071 | [(7S)-4,4-diphenyl-3,5-dioxabicyclo[5.1.0]oct-1-yl]methanol | C19H20O3 | 详情 | 详情 | |
| (VII) | 38072 | (1R,7S)-1-(bromomethyl)-4,4-diphenyl-3,5-dioxabicyclo[5.1.0]octane | C19H19BrO2 | 详情 | 详情 | |
| (VIII) | 38073 | 5-[(E)-2-bromoethenyl]-2,4(1H,3H)-pyrimidinedione | 69304-49-0 | C6H5BrN2O2 | 详情 | 详情 |
| (IX) | 38074 | 5-[(E)-2-bromoethenyl]-1-[[(7S)-4,4-diphenyl-3,5-dioxabicyclo[5.1.0]oct-1-yl]methyl]-2,4(1H,3H)-pyrimidinedione | C25H23BrN2O4 | 详情 | 详情 |