Citation: Li Li Zeng, Ying Jie Ding, Gui Cheng Zhang, Hong Rui Song, Wen Hui Hu. A practical synthesis of trifluorophenyl R-amino acid:The key precursor for the new anti-diabetic drug sitagliptin[J]. Chinese Chemical Letters, ;2009, 20(12): 1397-1399. doi: 10.1016/j.cclet.2009.06.036 shu

A practical synthesis of trifluorophenyl R-amino acid:The key precursor for the new anti-diabetic drug sitagliptin

a Laboratory of Anti-diabetic Drug Discovery, Center for Synthetic and Natural Drugs, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510663, China;
b The School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China

Received Date: 20 April 2009

Fund Project: This work was supported in part by grant from Science and Technology Program of Guangdong Province (No.2007B031503005).

Sitagliptin is the first new anti-diabetic drug in DPP-IV inhibitor class.The general synthesis of sitagliptin is by coupling of the β-amino acid fragment with the heterocycle fragment.Though the specific β-amino acid can be easily made from the corresponding R-amino acid by Arndt-Eistert homologation, the optically pure precursor R-amino acid is difficult to prepare.We herein reported a practical protocol to make the trifluorophenyl substituted R-amino acid 4 in >99.9% ee and 40.3% yield by the enzymatic resolution employing enantioselective hydrolysis and a general separation procedure.This protocol requires only cheap starting materials and friendly reaction condition.The procedure not only allows people to prepare the drug substance, but also provides an alternative method for prepareing the rare a-amino acid and the subsequent β-amino acid.
- Sitagliptin,
- β-Amino acid,
- DPP-IV inhibitor,
- Practical synthesis
1. [1]
  Jia-Cheng Hou , Hong-Tao Ji , Yu-Han Lu , Jia-Sheng Wang , Yao-Dan Xu , Yan-Yan Zeng , Wei-Min He . Sustainable and practical semi-heterogeneous photosynthesis of 5-amino-1,2,4-thiadiazoles over WS₂/TEMPO. Chinese Chemical Letters, 2024, 35(8): 109514-. doi: 10.1016/j.cclet.2024.109514
2. [2]
  Anqiu LIU , Long LIN , Dezhi ZHANG , Junyu LEI , Kefeng WANG , Wei ZHANG , Junpeng ZHUANG , Haijun HAO . Synthesis, structures, and catalytic activity of aluminum and zinc complexes chelated by 2-((2,6-dimethylphenyl)amino)ethanolate. Chinese Journal of Inorganic Chemistry, 2024, 40(4): 791-798. doi: 10.11862/CJIC.20230424
3. [3]
  Yiyue Ding , Qiuxiang Zhang , Lei Zhang , Qilu Yao , Gang Feng , Zhang-Hui Lu . Exceptional activity of amino-modified rGO-immobilized PdAu nanoclusters for visible light-promoted dehydrogenation of formic acid. Chinese Chemical Letters, 2024, 35(7): 109593-. doi: 10.1016/j.cclet.2024.109593
4. [4]
  Wenyi Mei , Lijuan Xie , Xiaodong Zhang , Cunjian Shi , Fengzhi Wang , Qiqi Fu , Zhenjiang Zhao , Honglin Li , Yufang Xu , Zhuo Chen . Design, synthesis and biological evaluation of fluorescent derivatives of ursolic acid in living cells. Chinese Chemical Letters, 2024, 35(5): 108825-. doi: 10.1016/j.cclet.2023.108825
5. [5]
  Kaimin WANG , Xiong GU , Na DENG , Hongmei YU , Yanqin YE , Yulu MA . Synthesis, structure, fluorescence properties, and Hirshfeld surface analysis of three Zn(Ⅱ)/Cu(Ⅱ) complexes based on 5-(dimethylamino) isophthalic acid. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1397-1408. doi: 10.11862/CJIC.20240009
6. [6]
  Chuan-Zhi Ni , Ruo-Ming Li , Fang-Qi Zhang , Qu-Ao-Wei Li , Yuan-Yuan Zhu , Jie Zeng , Shuang-Xi Gu . A chiral fluorescent probe for molecular recognition of basic amino acids in solutions and cells. Chinese Chemical Letters, 2024, 35(10): 109862-. doi: 10.1016/j.cclet.2024.109862
7. [7]
  Zhen Dai , Linzhi Tan , Yeyu Su , Kerui Zhao , Yushun Tian , Yu Liu , Tao Liu . Site-specific incorporation of reduction-controlled guest amino acids into proteins for cucurbituril recognition. Chinese Chemical Letters, 2024, 35(5): 109121-. doi: 10.1016/j.cclet.2023.109121
8. [8]
  Ze-Yuan Ma , Mei Xiao , Cheng-Kun Li , Adedamola Shoberu , Jian-Ping Zou . S-(1,3-Dioxoisoindolin-2-yl)O,O-diethyl phosphorothioate (SDDP): A practical electrophilic reagent for the phosphorothiolation of electron-rich compounds. Chinese Chemical Letters, 2024, 35(5): 109076-. doi: 10.1016/j.cclet.2023.109076
9. [9]
  Zhili Li , Qijun Wo , Dongdong Huang , Dezhong Zhou , Lei Guo , Yeqing Mao . Improving gene transfection efficiency of highly branched poly(β-amino ester)s through the in-situ conversion of inactive terminal groups. Chinese Chemical Letters, 2024, 35(8): 109737-. doi: 10.1016/j.cclet.2024.109737
10. [10]
  Huimin Luan , Qinming Wu , Jianping Wu , Xiangju Meng , Feng-Shou Xiao . Templates for the synthesis of zeolites. Chinese Journal of Structural Chemistry, 2024, 43(4): 100252-100252. doi: 10.1016/j.cjsc.2024.100252
11. [11]
  Zhaojun Liu , Zerui Mu , Chuanbo Gao . Alloy nanocrystals: Synthesis paradigms and implications. Chinese Journal of Structural Chemistry, 2023, 42(11): 100156-100156. doi: 10.1016/j.cjsc.2023.100156
12. [12]
  Zhenhao Wang , Yuliang Tang , Ruyu Li , Shuai Tian , Yu Tang , Dehai Li . Bioinspired synthesis of cochlearol B and ganocin A. Chinese Chemical Letters, 2024, 35(7): 109247-. doi: 10.1016/j.cclet.2023.109247
13. [13]
  Hui Jin , Qin Cai , Peiwen Liu , Yan Chen , Derong Wang , Weiping Zhu , Yufang Xu , Xuhong Qian . Multistep continuous flow synthesis of Erlotinib. Chinese Chemical Letters, 2024, 35(4): 108721-. doi: 10.1016/j.cclet.2023.108721
14. [14]
  Huipeng Zhao , Xiaoqiang Du . Polyoxometalates as the redox anolyte for efficient conversion of biomass to formic acid. Chinese Journal of Structural Chemistry, 2024, 43(2): 100246-100246. doi: 10.1016/j.cjsc.2024.100246
15. [15]
  Dan-Ying Xing , Xiao-Dan Zhao , Chuan-Shu He , Bo Lai . Kinetic study and DFT calculation on the tetracycline abatement by peracetic acid. Chinese Chemical Letters, 2024, 35(9): 109436-. doi: 10.1016/j.cclet.2023.109436
16. [16]
  Caihong Mao , Yanfeng He , Xiaohan Wang , Yan Cai , Xiaobo Hu . Synthesis and molecular recognition characteristics of a tetrapodal benzene cage. Chinese Chemical Letters, 2024, 35(8): 109362-. doi: 10.1016/j.cclet.2023.109362
17. [17]
  Mei Peng , Wei-Min He . Photochemical synthesis and group transfer reactions of azoxy compounds. Chinese Chemical Letters, 2024, 35(8): 109899-. doi: 10.1016/j.cclet.2024.109899
18. [18]
  Yiran Tao , Chunlei Dai , Zhaoxiang Xie , Xinru You , Kaiwen Li , Jun Wu , Hai Huang . Redox responsive polymeric nanoparticles enhance the efficacy of cyclin dependent kinase 7 inhibitor for enhanced treatment of prostate cancer. Chinese Chemical Letters, 2024, 35(8): 109170-. doi: 10.1016/j.cclet.2023.109170
19. [19]
  Jia Chen , Yun Liu , Zerong Long , Yan Li , Hongdeng Qiu . Colorimetric detection of α-glucosidase activity using Ni-CeO₂ nanorods and its application to potential natural inhibitor screening. Chinese Chemical Letters, 2024, 35(9): 109463-. doi: 10.1016/j.cclet.2023.109463
20. [20]
  Hanqing Zhang , Xiaoxia Wang , Chen Chen , Xianfeng Yang , Chungli Dong , Yucheng Huang , Xiaoliang Zhao , Dongjiang Yang . Selective CO2-to-formic acid electrochemical conversion by modulating electronic environment of copper phthalocyanine with defective graphene. Chinese Journal of Structural Chemistry, 2023, 42(10): 100089-100089. doi: 10.1016/j.cjsc.2023.100089

Get Citation

PDF

XML

Metrics

PDF Downloads(5)
Abstract views(511)
HTML views(47)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Address：Zhongguancun North First Street 2,100190 Beijing, PR China Tel: +86-010-82449177-888

DownLoad: Full-Size Img PowerPoint

Return