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【结 构 式】 
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【分子编号】68498 【品名】(3R,4S,5S)-methyl 3-acetoxy-4,5-dihydroxycyclohexanecarboxylate 【CA登记号】 |
【 分 子 式 】C10H16O6 【 分 子 量 】232.23344 【元素组成】C 51.72% H 6.94% O 41.34% |
合成路线1
该中间体在本合成路线中的序号：(XXII)The acceptor alcohol (XII) is synthesized by esterification of shikimic acid (XVI) with MeOH in the presence of H2SO4 to give methyl shikimate (XVII), which is then protected as the 3,4-acetonide (XIX) by transketalization with 2,2-dimethoxypropane (XVIII) by means of TsOH in acetonitrile. Hydrogenation of compound (XIX) over PtO2/C in MeOH affords the saturated ester (XX), which by acetylation with Ac2O in the presence of pyridine and DMAP in CH2Cl2 affords acetate (XXI). Deprotection of compound (XXI) by means of 80% aqueous AcOH at 80 °C provides diol (XXII), which is regioselectively converted to tosylate (XXIII) with TsCl in pyridine. Substitution of tosylate (XXIII) with NaN3 in DMF at 80 °C yields the corresponding azide (XXIV), which is then condensed with thioglycoside (XXV) by means of Br2 and Et4NBr in CH2Cl2/DMF/cyclohexene to obtain ether (XXVI). Finally, intermediate (XXVI) is submitted to deacetylation and simultaneous epimerization by means of NaOMe in MeOH, followed by reesterification with CH2N2 in Et2O .
| 【1】 Magnani, J.L., Patton, J.T. Jr., Sarkar, A.K., Svarovsky, S.A., Ernst, B. (GlycoMimetics, Inc.). Heterobifunctional pan-selectin inhibitors. EP 1934236, EP 2264043, JP 2009507031, US 2007054870, US 7728117, WO 2007028050. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XII) | 68493 | (1S,3S,4R,5R)-methyl 3-azido-5-hydroxy-4-(((2S,3S,4R,5S,6R)-3,4,5-tris(benzyloxy)-6-methyltetrahydro-2H-pyran-2-yl)oxy)cyclohexanecarboxylate | C35H41N3O8 | 详情 | 详情 | |
| (XVI) | 29907 | (3R,4S,5R)-3,4,5-trihydroxy-1-cyclohexene-1-carboxylic acid; Shikimic acid | 138-59-0 | C7H10O5 | 详情 | 详情 |
| (XVII) | 29908 | methyl (3R,4S,5R)-3,4,5-trihydroxy-1-cyclohexene-1-carboxylate | C8H12O5 | 详情 | 详情 | |
| (XVIII) | 10722 | 1-Methoxy-1-methylethyl methyl ether; 2,2-Dimethoxypropane | 77-76-9 | C5H12O2 | 详情 | 详情 |
| (XIX) | 29909 | methyl (3aR,7R,7aS)-7-hydroxy-2,2-dimethyl-3a,6,7,7a-tetrahydro-1,3-benzodioxole-5-carboxylate | C11H16O5 | 详情 | 详情 | |
| (XX) | 68500 | (3aS,7S,7aS)-methyl 7-hydroxy-2,2-dimethylhexahydrobenzo[d][1,3]dioxole-5-carboxylate | C11H18O5 | 详情 | 详情 | |
| (XXI) | 68499 | (3aS,7S,7aS)-methyl 7-acetoxy-2,2-dimethylhexahydrobenzo[d][1,3]dioxole-5-carboxylate | C13H20O6 | 详情 | 详情 | |
| (XXII) | 68498 | (3R,4S,5S)-methyl 3-acetoxy-4,5-dihydroxycyclohexanecarboxylate | C10H16O6 | 详情 | 详情 | |
| (XXIII) | 68497 | (3R,4S,5S)-methyl 3-acetoxy-4-hydroxy-5-(tosyloxy)cyclohexanecarboxylate | C17H22O8S | 详情 | 详情 | |
| (XXIV) | 68496 | (3R,4S,5R)-methyl 3-acetoxy-5-azido-4-hydroxycyclohexanecarboxylate | C10H15N3O5 | 详情 | 详情 | |
| (XXV) | 68502 | (3S,4S,5S,6R)-3,4,5-tris(benzyloxy)-2-(ethylthio)-6-methyltetrahydro-2H-pyran | C29H34O4S | 详情 | 详情 | |
| (XXVI) | 68501 | (3S,4S,5R)-methyl 3-acetoxy-5-azido-4-(((2R,3S,4S,5S,6R)-3,4,5-tris(benzyloxy)-6-methyltetrahydro-2H-pyran-2-yl)oxy)cyclohexanecarboxylate | C37H43N3O9 | 详情 | 详情 |