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【结 构 式】 
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【分子编号】16040 【品名】(3S)-N-[(4aR,6S,7R,8R,8aS)-6-(benzyloxy)-8-hydroxy-2-phenylhexahydropyrano[3,2-d][1,3]dioxin-7-yl]-3-hydroxytetradecanamide 【CA登记号】 |
【 分 子 式 】C34H49NO7 【 分 子 量 】583.7656 【元素组成】C 69.96% H 8.46% N 2.4% O 19.19% |
合成路线1
该中间体在本合成路线中的序号：(III)1) The reaction of benzyl 2-amino-4,6-O-benzylidene-2-deoxy-alpha-D-glucopyranoside (I) with 3(S)-hydroxytetradecanoic acid (II) by means of pivaloyl chloride in THF gives the corresponding amide (III), which is acylated with 9-phenylnonanoic acid (IV), dimethylaminopyridine (DMAP) and triethylamine (or tetramethylurea and oxalyl chloride) yielding the fully esterified compound (V). Elimination of the benzylidene group of (V) with HBF4/NaBF4 and the benzyl group by hydrogenolysis with H2 over Pd/C affords the trihydroxy compound (VI), which is treated with tert-butyldimethylsilyl chloride (TBDMS-Cl) and pyridine to give (VII) with the primary OH-group protected with a TBDMS group. The sulfonation of (VII) with SO3/pyridine complex affords the sulfonated compound (VIII), which is finally desilylated with acetic acid in ethanol.
| 【1】 Graul, A.; Martel, A.M.; Castaner, J.; ONO-4007. Drugs Fut 1997, 22, 8, 841. |
| 【2】 Imaki, K.; Hashimoto, S.; Wakatsuka, H. (Ono Pharmaceutical Co., Ltd.); Salts of glucopyranose deriv. and its intermediate. EP 0553786; JP 1994041175; US 5733927 . |
| 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) | 16038 | (4aR,6S,7R,8R,8aS)-7-amino-6-(benzyloxy)-2-phenylhexahydropyrano[3,2-d][1,3]dioxin-8-ol | C20H23NO5 | 详情 | 详情 | |
| (II) | 16039 | (3S)-3-hydroxytetradecanoic acid | 1961-72-4 | C14H28O3 | 详情 | 详情 |
| (III) | 16040 | (3S)-N-[(4aR,6S,7R,8R,8aS)-6-(benzyloxy)-8-hydroxy-2-phenylhexahydropyrano[3,2-d][1,3]dioxin-7-yl]-3-hydroxytetradecanamide | C34H49NO7 | 详情 | 详情 | |
| (IV) | 16041 | 9-phenylnonanoic acid | C15H22O2 | 详情 | 详情 | |
| (V) | 16042 | (1S)-1-[2-([(4aR,6S,7R,8R,8aR)-6-(benzyloxy)-2-phenyl-8-[(9-phenylnonanoyl)oxy]hexahydropyrano[3,2-d][1,3]dioxin-7-yl]amino)-2-oxoethyl]dodecyl 9-phenylnonanoate | C64H89NO9 | 详情 | 详情 | |
| (VI) | 16043 | (3R,4R,5R,6R)-2,5-dihydroxy-6-(hydroxymethyl)-3-([(3S)-3-[(9-phenylnonanoyl)oxy]tetradecanoyl]amino)tetrahydro-2H-pyran-4-yl 9-phenylnonanoate | C50H79NO9 | 详情 | 详情 | |
| (VII) | 16044 | (2R,3R,4R,5R)-2-([[tert-butyl(dimethyl)silyl]oxy]methyl)-3,6-dihydroxy-5-([(3S)-3-[(9-phenylnonanoyl)oxy]tetradecanoyl]amino)tetrahydro-2H-pyran-4-yl 9-phenylnonanoate | C56H93NO9Si | 详情 | 详情 | |
| (VIII) | 16052 | 6-O-(Tert-butyldimethylsilyl)-2-deoxy-3-O-(9-phenylnonanoyl)-2-[3(S)-(9-phenylnonanoyloxy)tetradecanamido]-4-O-sulfo-D-glucopyranose sodium salt | C56H92NNaO12SSi | 详情 | 详情 |