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【结 构 式】 
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【分子编号】11332 【品名】3-(Hexadecylsulfanyl)-2-(methoxymethyl)-1-propanol 【CA登记号】 |
【 分 子 式 】C21H44O2S 【 分 子 量 】360.64516 【元素组成】C 69.94% H 12.3% O 8.87% S 8.89% |
合成路线1
该中间体在本合成路线中的序号：(VII)An improved synthesis of ilmofosine has been reported: The reaction of 2-(hydroxymethyl)-2-propenoic acid ethyl ester (I) with PBr3 in ethyl ether gives the corresponding 2-bromomethyl derivative (II), which is condensed with hexadecylthiol (III) by means of triethylamine to afford 2-(hexadecylsulfanyl)-2-propenoic acid ethyl ester (IV). The reduction of (IV) with diisobutylaluminum hydride (DIBAL) yields 3-(hexadecylsulfanyl)-2-methylene-1-propanol (V), which is methylated with NaH and MeI to the methyl ether (VI). The hydroboration of (VI) with BH3.S(CH3)2 followed by oxidation with NaBO3 gives 3-(hexadecylsulfanyl)-2-(methoxymethyl)-1-propanol (VII), which is finally phosphorylated with PCl3 and condensed with choline p-toluenesulfonate (VIII).
| 【1】 Reddy, K.C.; Byun, H.S.; Bittman, R.; Antitumor ether lipids: An improved synthesis of ilmofosine and an enantioselective synthesis of an ilmofosine analog. Tetrahedron Lett 1994, 35, 17, 2679. |
| 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) | 11327 | ethyl 2-(hydroxymethyl)acrylate | 10029-04-6 | C6H10O3 | 详情 | 详情 |
| (II) | 11328 | ethyl 2-(bromomethyl)acrylate | 17435-72-2 | C6H9BrO2 | 详情 | 详情 |
| (III) | 41266 | 1-hexadecanethiol; hexadecylhydrosulfide | 2917-26-2 | C16H34S | 详情 | 详情 |
| (IV) | 11329 | ethyl 2-[(hexadecylsulfanyl)methyl]acrylate | C22H42O2S | 详情 | 详情 | |
| (V) | 11330 | 2-[(Hexadecylsulfanyl)methyl]-2-propen-1-ol | C20H40OS | 详情 | 详情 | |
| (VI) | 11331 | 2-[(Hexadecylsulfanyl)methyl]-2-propenyl methyl ether; 3-(Hexadecylsulfanyl)-2-(methoxymethyl)-1-propene | C21H42OS | 详情 | 详情 | |
| (VII) | 11332 | 3-(Hexadecylsulfanyl)-2-(methoxymethyl)-1-propanol | C21H44O2S | 详情 | 详情 | |
| (VIII) | 11333 | N,N,N-Trimethyl-2-[(phenylsulfonyl)oxy]-1-ethanaminium chloride | C11H18ClNO3S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VI)The reaction of 2-(hydroxymethyl)propenoic acid ethyl ester (I) with PBr3 and then with hexadecyl mercaptane (II) and TEA gives 2-(hexadecylsulfanylmethyl)propenoic acid methyl ester (III), which is reduced with DIBAL in THF to the corresponding carbinol (IV). The methylation of (IV) with methyl iodide and NaH in THF affords the methyl ether (V), which is hydroxylated at the double bond with BH3/Me2S and NaBO3 providing 3-(hexadecylsulfanyl)-2-(methoxymethyl)-1-propanol (VI). Finally this compound is treated with POCl3 and TEA in chloroform and condensed with choline tosylate (VII) to furnish the target phosphorylcholine derivative.
| 【1】 Bittman, R.; Lohmeyer, M.; Antitumor ether lipids and alkylphosphocholines. Drugs Fut 1994, 19, 11, 1021. |
| 【2】 Reddy, K.C.; Byun, H.S.; Bittman, R.; Antitumor ether lipids: An improved synthesis of ilmofosine and an enantioselective synthesis of an ilmofosine analog. Tetrahedron Lett 1994, 35, 17, 2679. |
| 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) | 11327 | ethyl 2-(hydroxymethyl)acrylate | 10029-04-6 | C6H10O3 | 详情 | 详情 |
| (II) | 41266 | 1-hexadecanethiol; hexadecylhydrosulfide | 2917-26-2 | C16H34S | 详情 | 详情 |
| (III) | 11329 | ethyl 2-[(hexadecylsulfanyl)methyl]acrylate | C22H42O2S | 详情 | 详情 | |
| (IV) | 11330 | 2-[(Hexadecylsulfanyl)methyl]-2-propen-1-ol | C20H40OS | 详情 | 详情 | |
| (V) | 11331 | 2-[(Hexadecylsulfanyl)methyl]-2-propenyl methyl ether; 3-(Hexadecylsulfanyl)-2-(methoxymethyl)-1-propene | C21H42OS | 详情 | 详情 | |
| (VI) | 11332 | 3-(Hexadecylsulfanyl)-2-(methoxymethyl)-1-propanol | C21H44O2S | 详情 | 详情 | |
| (VII) | 41265 | 2-hydroxy-N,N,N-trimethyl-1-ethanaminium 4-methylbenzenesulfonate | C12H21NO4S | 详情 | 详情 |