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【结 构 式】 
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【分子编号】68565 【品名】(2S,3R,4R,5S)-2-(acetoxymethyl)-6-((tetrahydro-2H-pyran-2-yl)oxy)tetrahydro-2H-thiopyran-3,4,5-triyltriacetate 【CA登记号】 |
【 分 子 式 】C19H28O10S 【 分 子 量 】448.491 【元素组成】C 50.88% H 6.29% O 35.67% S 7.15% |
合成路线1
该中间体在本合成路线中的序号：(XV)Thiolactone (VI) can be prepared as follows. Selective removal of the anomeric acetyl group of 1,2,3,4,6-penta-O-acetyl-5-thio-D-glucopyranose (XIII) by means of MeNHNH2 in the presence of AcOH in DMF and then protection of the resulting hydroxyl group with DHP in the presence of p-TsOH.H2O in CHCl3 affords the tetrahydropyranyl ether (XV). Zemplen deacetylation of the tetra-O-acetate (XV) with NaOMe in MeOH, and subsequent protection of the resulting hydroxyl groups with PhCH2Br by means of NaH in DMF provides the tetrabenzyl ether (XVI), which by removal of the THP-protecting group with PPTS in EtOH at 80 °C generates 2,3,4,6-tetra-O-benzyl-5-thio-D-glucopyranose (XVII). Finally, thioglucopyranose (XVII) is oxidized with DMSO in the presence of Ac2O .
| 【1】 Kakinuma, H., Oi, T., Hashimoto-Tsuchiya, Y. et al. (1S)-1,5-Anhydro-1-[5-(4-ethoxybenzyl)-2-methoxy-4-methylphenyl]-1-thio-D- glucitol (TS-071) is a potent, selective sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor for type 2 diabetes treatment. J Med Chem 2010, 53(8): 3247-61. |
| 【2】 Kakinuma, H., Hashimoto, Y., Oi, T., Hirano, H. (Taisho Pharmaceutical Co., Ltd.). 1-Thio-D-glucitol derivatives. EP 1845095, JP 2010059173, US 2008132563, US 7910619, US 2011098469, US 8017792, WO 2006073197. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 68556 | (3S,4R,5S,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-thiopyran-2-one | C34H34O5S | 详情 | 详情 | |
| (XIII) | 68567 | (3S,4R,5R,6S)-6-(acetoxymethyl)tetrahydro-2H-thiopyran-2,3,4,5-tetrayl tetraacetate | C16H22O10S | 详情 | 详情 | |
| (XIV) | 68566 | (3S,4R,5R,6S)-2-(acetoxymethyl)-6-hydroxytetrahydro-2H-thiopyran-3,4,5-triyl triacetate | C14H20O9S | 详情 | 详情 | |
| (XV) | 68565 | (2S,3R,4R,5S)-2-(acetoxymethyl)-6-((tetrahydro-2H-pyran-2-yl)oxy)tetrahydro-2H-thiopyran-3,4,5-triyltriacetate | C19H28O10S | 详情 | 详情 | |
| (XVI) | 68564 | 2-(((3S,4R,5S,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-thiopyran-2-yl)oxy)tetrahydro-2H-pyran | C39H44O6S | 详情 | 详情 | |
| (XVII) | 68563 | (3S,4R,5S,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-thiopyran-2-ol | C34H36O5S | 详情 | 详情 |