| 第 36 卷第 2 期 |  | Vol. 36 No. 2 | | 2006 年 4 月 | Apr 2006 |
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所屬欄目：醫藥及中間體
從β-胸苷出發(fā)的司他夫定的合成工藝研究 |
| 施小新; 劉世領(lǐng); 陳艷; 易飛; 呂霞; 虞心紅(華東理工大學(xué)化學(xué)與制藥學(xué)院) |
| 摘 要：首先β-胸苷與1.5mol的三苯基氯甲烷和1.5mol的吡啶在DMF中反應,生成5′-位羥基的醚化產(chǎn)物(2);化合物2再在三乙胺作用下與2mol的甲烷磺酰氯反應制成甲磺酸酯(3);然后,化合物3在乙醇中與等摩爾的氫氧化鈉作用,制備成氧橋化合物(4);化合物4在DMSO中,在2mol的甲醇鈉作用下,生成消除反應產(chǎn)物5;化合物3也可在DMSO中與4mol的甲醇鈉作用,一步直接得到消除產(chǎn)物5;最后,化合物5脫保護制備得到司他夫定(d4T,1)。當合成采取“β-胸苷→2→3→4→5→1”路線(xiàn)時(shí),五步反應總收率為74%。當合成采取“β-胸苷→2→3→5→1”路線(xiàn)時(shí),四步反應總收率為70%。 |
| 關(guān)鍵詞：司他夫定; β-胸苷; HIV逆轉錄酶抑制劑; 合成 |
| 中圖分類(lèi)號：TQ463+54 文獻標識碼：A 文章編號：1009-9212(2006)02-0014-04 |
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| A Practical Synthesis of Stavudine(d4T) from β-Thymidine |
| SHI Xiao-Xin; LIU Shi-Ling; CHEN Yan; YI Fei; LU Xia; YU Xin-Hong（College of Chemistry and Pharmaceutical Engineering; East China University of Science and Technology; Shanghai 200237; China） |
| Abstract：A practical synthesis of stavudine (d4T) was described. β-Thymidine was treated with 1.5 equiv of Ph3CCl in DMF in the presence of pyridine to form 5′-O-trityl thymidine (2) in 93% yield. The compound 2 then reacted with 2 equiv. of methylsulfonyl chloride and 3 equiv. of Et3N to produce 3′-O-methylsulfonyl-5′-O-trityl thymidine (3) in 98% yield. After the compound 3 was converted into 2,3′-anhydro-5′-O-trityl thymidine(4)in 95% yield by refluxing with equal equiv. of NaOH in ethanol, the compound 4 was the... |
| Key words：stavudine（d4T）; β-thymidine; HIV reverse transcriptase inhibitors; synthesis |
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基金項目：國家自然科學(xué)基金(No.A-20172015);上海市教育發(fā)展基金(No:03SG27)。
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收稿日期：2005-12-10
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