| 第 48 卷第 6 期 |  | Vol. 48 No. 6 | | 2018 年 12 月 | Dec 2018 |
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所屬欄目：醫藥及中間體
特力利汀關(guān)鍵中間體（2S）-4-氧代-2-（3-噻唑烷基羰基）-1-吡咯烷羧酸叔丁酯的合成研究 |
| 崔哲凱，卓廣瀾
（浙江理工大學(xué) 理學(xué)院，浙江 杭州 310018） |
| 摘 要：以4-羥基-L-脯氨酸和半胱胺鹽酸鹽為起始原料，經(jīng)過(guò)氨基的保護、氧化、縮合3步反應得到合成特力利汀的關(guān)鍵中間體（2S）-4-氧代-2-（3-噻唑烷基羰基）-1-吡咯烷羧酸叔丁酯，總收率73.8%。采用了新的合成策略，對氧化方法進(jìn)行了研究?jì)?yōu)化。整體路線(xiàn)環(huán)境污染小、對設備腐蝕小、產(chǎn)品收率高，適于工業(yè)化推廣。其結構經(jīng)1H NMR和ESI-MS確證。 |
| 關(guān)鍵詞：特力利汀中間體；4-羥基-L-脯氨酸；氧化；（2S）-4-氧代-2-（3-噻唑烷基羰基）-1-吡咯烷羧酸叔丁酯 |
| 中圖分類(lèi)號：0624.6；R914.5 文獻標識碼：A 文章編號：1009-9212（2018）06-0036-04 |
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| Synthesis of the Key Intermediate (2S)-4-Oxo-2-(3-thiazolidinylcarbonyl)-1-pyrrolidinecarboxylic acid tert-butyl ester of Teneligliptin |
| CUI Zhe-kai, ZHUO Guang-lan*
(Zhejiang Sci-Tech University, College of Science, Hangzhou 310018, China) |
| Abstract：The key intermediate of Teneligliptin, (2S)-4-oxo-2-(3-thiazolidinylcarbonyl)-1-pyrrolidinecarboxylic acid tert-butyl ester, was synthesized from trans-4-hydroxy-L-proline and cysteamine hydrochloride in three steps including amino protection, oxidation, condensation. The overall yield from this synthetic route was 73.8%. The new strategy used in this method had the advantages including less pollution, lower corrosion, and high yield. It was suitable for industrial application. At the same time, we discussed and optimized the oxidation method. The structure was confirmed by 1H NMR and ESI-MS. |
| Key words：intermediate of Teneligliptin; 4-hydroxy-L-proline; oxidation; (2S)-4-oxo-2-(3-thiazolidinylcarbonyl)-1-pyrrolidinecarboxylic acid tert-butyl ester |
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作者簡(jiǎn)介：崔哲凱（1993-），男，內蒙古赤峰人，碩士研究生，研究方向：精細有機合成（E-mail：15988172114@163.com）。
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聯(lián) 系 人：卓廣瀾，副教授，研究方向：精細有機合成。
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收稿日期：2018-11-28
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