达格列净合成工艺的改进
A new synthetic process of dapagliflozin
-
摘要: 对SGLT2抑制剂达格列净的合成工艺进行改进。以1-氯-2-(4-乙氧基苄基)-4-碘苯和2，3，4，6-四乙酰氧基-α-D-溴代吡喃葡萄糖为原料，经格式交换，催化偶联以及乙酰基脱除反应，得到达格列净，总收率50%。本工艺反应步骤少，产生废料少，反应条件温和。Abstract: This paper describes a practical process for a SGLT2 inhibitor dapagliflozin. The target product was synthesized from 1-chloro-2-(4-ethoxybenzyl)-4-iodobenzene and 2, 3, 4, 6-tetra-O-acetyl-alpha-D-glucopyranosyl bromide by iodine-magnesium exchange, and coupling and acetyl removing reactions with the total yield of 50%. This practical process highlights fewer reaction steps, less waste and mild reaction conditions.
-
Keywords:
- SGLT2 inhibitors /
- dapagliflozin /
- synthesis /
- process improvement /
- antidiabetic agents
-
-
[1] Tang Q,Li X,Song P,et al.Optimal cut-off values for the homeostasis model assessment of insulin resistance(HOMA-IR)and pre-diabetes screening:developments in research and prospects for the future[J].Drug Discov Ther,2015,9(6):380-384. [2] Mather A,Pollock C.Glucose handling by the kidney[J].Kidney Int Suppl,2011,79(2):S1-S6. [3] Meng W,Ellsworth BA,Nirschl AA,et al.Discovery of dapagliflozin:a potent,selective renal sodium-dependent glucose cotransporter 2(SGLT2)inhibitor for the treatment of type 2 diabetes[J].J Med Chem,2008, 51(5):1145-1149. [4] Xu BH,Lv BH,Xu G,et al.Process for preparation of benzylbenzene sodium-dependent glucose cotransporter 2(SGLT2)inhibitors:WO,2013152476[P].2013-10-17. [5] Lemaire S,Houpis IN,Xiao T,et al.Stereoselective C-glycosylation reactions with arylzinc reagents[J].Org Lett,2012, 14(6):1480-1483. [6] Zhang WW,Dai ZQ,Zhang ZY,et al.Progress in transition-metal-catalyzed cross-coupling reaction of grignard reagent with halides[J].Chem World(化学世界),2001,52(3):314-316. -
期刊类型引用(9)
1. 戴建英. 在体单向肠灌流法研究知母提取物肠吸收特性. 湖北医药学院学报. 2024(05): 518-523 . 
百度学术
2. 黄秋妹，石茗，王珍，倪明龙，阙慧卿. 吴茱萸碱制剂的研究进展. 广东化工. 2023(10): 66-68+79 . 百度学术
3. 黄秋妹，阙慧卿，李唯，钱丽萍，刘经亮. 吴茱萸碱脂质体的制备工艺研究. 医学信息. 2023(19): 19-22 . 百度学术
4. 张佩琛，方栋，郝海军. 吴茱萸碱胃漂浮片制备及其对家兔胃黏膜损伤的保护作用. 中成药. 2023(11): 3527-3533 . 百度学术
5. 董丹丹，焦红军，郝海军，范明松. 吴茱萸碱纳米结构脂质载体处方优化和SD大鼠体内口服药动学研究. 中草药. 2022(01): 60-70 . 百度学术
6. 宋朔尧，杨贵前，陶玲，沈祥春，张环，李和蓉，王守莉，石惠云，刘文. 吴茱萸碱磷脂复合物自乳化药物递送系统的制备、表征及胃黏膜渗透性研究. 中国药房. 2022(09): 1056-1061 . 百度学术
7. 赵梦，刘卓雅，于嘉敏，王芮，范铭婕，乔宏志. 生姜细胞外囊泡样纳米粒载吴茱萸碱的处方工艺及体外释药研究. 南京中医药大学学报. 2022(06): 527-533 . 百度学术
8. 决利利，梁婧，李晓婷，王柯静，周珊珊，刘艳菊. 松果菊苷固体脂质纳米粒的制备及其在体肠吸收特性、体内药动学研究. 中成药. 2022(08): 2429-2434 . 百度学术
9. 陈云，曾梅，徐靖鑫，胡娟，张景勍. 二甲双胍-白藜芦醇复合物油包水型纳米乳在体肠吸收及其药代动力学研究. 中国药科大学学报. 2021(03): 325-331 . 本站查看
其他类型引用(2)
计量
- 文章访问数: 1002
- HTML全文浏览量: 0
- PDF下载量: 2978
- 被引次数: 11
下载:
