| 李博洋,闵清,王刚,邵开元,胡文祥.化学通报,2022,85(2):235-239. |
| 小檗碱C(9)位硫辛酸酯类化合物的设计合成及量子化学计算研究 |
| Design Synthesis and Quantum Chemical Calculationsof C (9) Lipoic Acid Esters of Berberine |
| 投稿时间：2021-04-16 修订日期：2021-07-12 |
| DOI： |
| 中文关键词: 小檗碱C(9)结构修饰 量子化学计算 降糖抗氧化 |
| 英文关键词:Berberine C(9) structure modification, Quantum chemistry calculation, Hypoglycemic and antioxidant |
| 基金项目: |
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| 摘要点击次数: 947 |
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| 中文摘要: |
| 摘要 目的：现代医学研究证实，小檗碱具有显著的降糖活性和临床安全性。目前，临床应用的降糖药物能够有效控制血糖，但使用不方便，副作用的问题难以避免，且对胰岛素分泌不足、胰岛素抵抗等问题研究少之甚少。方法：本文以小檗碱为先导化合物，对小檗碱C(9)进行结构修饰，并在相应的位点引入具有抗氧化作用的硫辛酸，设计合成了小檗碱 C(9) 位硫辛酸酯及其类似物，以期希望能够合成出一种具有双功能双位点的新型降糖药物，已到达修复和改善胰岛功能。结果：本文共合成2个小檗碱硫辛酸酯衍生物，且均未见文献报道，并用 LC-MS、1H-NMR、13C-NMR对其结构进行了表征。中间体9-O-取代基类BBR的合成是反应中关键一步，通过量子化学计算比较三种试剂的亲电反应能力，通过比较1,2-二溴乙烷亲电能力最高，其次是2-溴乙醇，最低的为环氧乙烷，为后续中间体的合成工艺提供初步理论依据。 |
| 英文摘要: |
| Abstract Objective: modern medical research has confirmed that berberine has significant glucose lowering activity and clinical safety.At present, clinically used hypoglycemic drugs can effectively control blood glucose, but the problems of inconvenient use, side effects are difficult to avoid, and few studies have focused on the problems of insufficient insulin secretion and insulin resistance. Method：In this paper, berberine C (9) was structurally modified as a lead compound, and lipoic acid with antioxidant effect was introduced at the corresponding site, and lipoate and its analogues at the C (9) position of berberine were designed and synthesized, with the hope of synthesizing a novel glucose lowering drug with dual functional dual sites, which had reached the goal of repairing and improving pancreatic islet function.Results: in this paper, two lipoate derivatives of berberine were synthesized, all of which have not been reported in the literature, and their structures were characterized by LC-MS, 1H-NMR, and 13C-NMR.The synthesis of intermediate 9-o-substituent type BBR is the key step in the reaction, by comparing the electrophilic reaction ability of the three reagents through quantum chemical calculations, by comparing the 1,2-dibromoethane electrophilic ability is the highest, followed by 2-bromoethanol, and the lowest is oxirane, which provides a preliminary theoretical basis for the synthesis process of subsequent intermediates. |
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