高级检索

达格列净合成工艺的改进

马力, 张梦晗, 许志伟, 孙英爱, 朱静, 黄英博, 张大永

马力, 张梦晗, 许志伟, 孙英爱, 朱静, 黄英博, 张大永. 达格列净合成工艺的改进[J]. 中国药科大学学报, 2017, 48(1): 42-45. DOI: 10.11665/j.issn.1000-5048.20170106
引用本文: 马力, 张梦晗, 许志伟, 孙英爱, 朱静, 黄英博, 张大永. 达格列净合成工艺的改进[J]. 中国药科大学学报, 2017, 48(1): 42-45. DOI: 10.11665/j.issn.1000-5048.20170106
MA Li, ZHANG Menghan, XU Zhiwei, SUN Ying′ai, ZHU Jing, HUANG Yingbo, ZHANG Dayong. A new synthetic process of dapagliflozin[J]. Journal of China Pharmaceutical University, 2017, 48(1): 42-45. DOI: 10.11665/j.issn.1000-5048.20170106
Citation: MA Li, ZHANG Menghan, XU Zhiwei, SUN Ying′ai, ZHU Jing, HUANG Yingbo, ZHANG Dayong. A new synthetic process of dapagliflozin[J]. Journal of China Pharmaceutical University, 2017, 48(1): 42-45. DOI: 10.11665/j.issn.1000-5048.20170106

达格列净合成工艺的改进

基金项目: 国家自然科学基金资助项目(No.81172934)

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.
  • [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.
计量
  • 文章访问数:  1007
  • HTML全文浏览量:  0
  • PDF下载量:  2978
  • 被引次数: 0
出版历程
  • 刊出日期:  2017-02-24

目录

    /

    返回文章
    返回
    x 关闭 永久关闭