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【结 构 式】 
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【药物名称】 【化学名称】N-[1(R)-(Hydroxymethyl)-2-oxo-2-(8-oxo-1-oxaspiro[2.5]octa-4,6-dien-5-ylamino)ethyl]decanamide 【CA登记号】 【 分 子 式 】C20H30N2O5 【 分 子 量 】378.4725 |
【开发单位】Universität Karlsruhe (Originator) 【药理作用】PHARMACOLOGICAL TOOLS, Neutral Sphingomyelinase (N-SMase) Inhibitors |
合成路线1
Coupling of decanoylchloride (I) with D-serine (II) under Schotten-Baumann conditions (with Na2CO3 in H2O/THF) provides N-decanoyl-D-serine (III). Separately, aldehyde (IV) is reduced by means of NaBH4 in EtOH to yield alcohol (V), whose nitro group is reduced by means of In and NH4Cl in EtOH to afford substituted aniline (VI). Coupling of 5-amino-2-hydroxybenzyl alcohol (VI) with serine (III) by means of dicyclohexylcarbodiimide (DCC) and 1-hydroxybenzotriazole (HOBt) in DMF furnishes compound (VII), which is finally oxidized with NaIO4 in MeOH/H2O to yield the desired spiroepoxide.
| 【1】 Giannis, A.; Arenz, C.; Synthesis of the first selective irreversible inhibitor of neutral sphingomyelinase. Angew Chem. Int Ed Engl 2000, 39, 8, 1440. |
| 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) | 28271 | decanoyl chloride | 112-13-0 | C10H19ClO | 详情 | 详情 |
| (II) | 15728 | (+)-2-Amino-3-hydroxypropionic acid; D-(+)-Serine; D-serine | 312-84-5 | C3H7NO3 | 详情 | 详情 |
| (III) | 47198 | (2R)-2-(decanoylamino)-3-hydroxypropionic acid | C13H25NO4 | 详情 | 详情 | |
| (IV) | 42307 | 2-hydroxy-5-nitrobenzaldehyde；5-nitrosalicylaldehyde | 97-51-8 | C7H5NO4 | 详情 | 详情 |
| (V) | 47199 | 2-(hydroxymethyl)-4-nitrophenol | C7H7NO4 | 详情 | 详情 | |
| (VI) | 47200 | 4-amino-2-(hydroxymethyl)phenol | C7H9NO2 | 详情 | 详情 | |
| (VII) | 47201 | N-[(1R)-2-[4-hydroxy-3-(hydroxymethyl)anilino]-1-(hydroxymethyl)-2-oxoethyl]decanamide | C20H32N2O5 | 详情 | 详情 |