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【结 构 式】 
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【药物名称】 【化学名称】3-Isopropyl-4-methylpentanoic acid [2-(hydroxymethyl)-4-[(Z)-3-isopropyl-4-methylpentylidene]-5-oxotetrahydrofuran-2-yl]methyl ester 【CA登记号】253603-03-1 【 分 子 式 】C24H42O5 【 分 子 量 】410.59934 |
【开发单位】National Institutes of Health (Originator) 【药理作用】ONCOLYTIC DRUGS, Inhibitors of Signal Transduction Pathways, Protein Kinase C Activators |
合成路线1
Addition of vinylmagnesium bromide to diisopropyl ketone (I) produced carbinol (II). Subsequent oxidation of (II) with pyridinium chlorochromate gave unsaturated aldehyde (III), which was further hydrogenated to the saturated aldehyde (IV). Optionally, oxidation with sodium chlorite produced carboxylic acid (V), which was converted to acid chloride (VI) using oxalyl chloride and pyridine.
| 【1】 Marquez, V.E.; Bienfait, B.; Lewin, N.E.; Benzaria, S.; Bhattacharyya, D.K.; Lee, J.; Nacro, K.; Han, K.-C.; Kang, J.-H.; Blumberg, P.M.; Conformationally constrained analogues of diacylglycerol (DAG). 16. How much structural complexity is necessary for recognition and high binding affinity to protein kinase C?. J Med Chem 2000, 43, 5, 921. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 16524 | bromo(vinyl)magnesium | 1826-67-1 | C2H3BrMg | 详情 | 详情 | |
| (I) | 39314 | 2,4-dimethyl-3-pentanone | 565-80-0 | C7H14O | 详情 | 详情 |
| (II) | 39315 | 3-isopropyl-4-methyl-1-penten-3-ol | C9H18O | 详情 | 详情 | |
| (III) | 39316 | 3-isopropyl-4-methyl-2-pentenal | C9H16O | 详情 | 详情 | |
| (IV) | 39317 | 3-isopropyl-4-methylpentanal | C9H18O | 详情 | 详情 | |
| (V) | 39318 | 3-isopropyl-4-methylpentanoic acid | C9H18O2 | 详情 | 详情 | |
| (VI) | 39319 | 3-isopropyl-4-methylpentanoyl chloride | C9H17ClO | 详情 | 详情 |
合成路线2
Aldol condensation of silylated lactone (VII) with aldehyde (IV) gave hydroxy lactone (VIII). Subsequent hydroxyl group mesylation followed by elimination in the presence of DBU generated alkylidene lactone (IXa-b) as a mixture of geometric isomers, which were separated by chromatography. Desilylation of (IX) to afford diol (X) was achieved by means of HF/pyridine. Finally, monoacylation of (X) with acid chloride (VI) and pyridine furnished the target ester.
| 【1】 Marquez, V.E.; Bienfait, B.; Lewin, N.E.; Benzaria, S.; Bhattacharyya, D.K.; Lee, J.; Nacro, K.; Han, K.-C.; Kang, J.-H.; Blumberg, P.M.; Conformationally constrained analogues of diacylglycerol (DAG). 16. How much structural complexity is necessary for recognition and high binding affinity to protein kinase C?. J Med Chem 2000, 43, 5, 921. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IXa) | 39322 | 5,5-bis([[tert-butyl(diphenyl)silyl]oxy]methyl)-3-[(E)-3-isopropyl-4-methylpentylidene]dihydro-2(3H)-furanone | C47H62O4Si2 | 详情 | 详情 | |
| (IXb) | 39323 | 5,5-bis([[tert-butyl(diphenyl)silyl]oxy]methyl)-3-[(Z)-3-isopropyl-4-methylpentylidene]dihydro-2-furanone | C47H62O4Si2 | 详情 | 详情 | |
| (IV) | 39317 | 3-isopropyl-4-methylpentanal | C9H18O | 详情 | 详情 | |
| (VI) | 39319 | 3-isopropyl-4-methylpentanoyl chloride | C9H17ClO | 详情 | 详情 | |
| (VII) | 39320 | 5,5-bis([[tert-butyl(diphenyl)silyl]oxy]methyl)dihydro-2(3H)-furanone | C38H46O4Si2 | 详情 | 详情 | |
| (VIII) | 39321 | 5,5-bis([[tert-butyl(diphenyl)silyl]oxy]methyl)-3-(1-hydroxy-3-isopropyl-4-methylpentyl)dihydro-2(3H)-furanone | C47H64O5Si2 | 详情 | 详情 | |
| (X) | 39324 | 5,5-bis(hydroxymethyl)-3-[(Z)-3-isopropyl-4-methylpentylidene]dihydro-2-furanone | C15H26O4 | 详情 | 详情 |