Synthesis of (S)-, (R)-, and (rac)-2-amino-3,3-bis(4-fluorophenyl)propanoic acids and an evaluation of the DPP IV inhibitory activity of Denagliptin diastereomers

doi:10.1016/j.tet.2008.08.097

	Synthesis of (S)-, (R)-, and (rac)-2-amino-3,3-bis(4-fluorophenyl)propanoic acids and an evaluation of the DPP IV inhibitory activity of Denagliptin diastereomers
	Deng, Guanghui 3; Ye, Deju 3; Li, Yuanyuan 1; He, Lingyan 3; Zhou, Yu3,4 ; Wang, Jiang3 ; Li, Jia1 ; Jiang, Hualiang2,3 ; Liu, Hong3
刊名	TETRAHEDRON
	2008-11-10
卷号	64 期号:46 页码:10512-10516
ISSN号	0040-4020
DOI	10.1016/j.tet.2008.08.097
文献子类	Article
英文摘要	The non-proteinogenic amino acid (2S)-2-amino-3,3-bis(4-fluorophenyl)propanoic acid [(S)-1] is a key intermediate required for the synthesis of Denagliptin (2a). Denagliptin is a dipeptidyl peptidase IV (DPP IV) inhibitor that is being developed for the treatment of type-2 diabetes mellitus. A diastereoselective, cost-efficient synthetic procedure for (S)-1 was developed by alkylating a Ni(II) glycine equivalent derived from (S)-2-[(N-benzylprolyl) amino] benzophenone [(S)-BPB]. The alkylated product was then decomposed to isolate the target amino acid (S)-1 (ee > 99%) and ligand (S)-BPB, which can be reused in subsequent reactions. The enantiomer (R)-1 and racemate (rac)-1 were synthesized from their corresponding Ni(II) glycine equivalents. Denagliptin diastereomers (2), derived from the key intermediates (S)-1, (R)-1, and (rac)-1 were synthesized, and their dipeptidyl peptidase IV inhibitory activities were investigated. These findings are important in the design and synthesis of DPP IV inhibitors. (c) 2008 Elsevier Ltd. All rights reserved.
资助项目	State Key Program of Basic Research of China[2002CB512802] ; National Natural Science Foundation of China[20372069] ; National Natural Science Foundation of China[29725203] ; National Natural Science Foundation of China[20472094] ; 863 Hi-Tech Program[2006AA020402] ; 863 Hi-Tech Program[2006AA020602]
WOS关键词	DIPEPTIDYL-PEPTIDASE-IV ; ALPHA-AMINO-ACIDS ; EFFICIENT ASYMMETRIC-SYNTHESIS ; NUCLEOPHILIC GLYCINE ; CHIRAL EQUIVALENTS ; NI(II) COMPLEXES ; DISCOVERY ; POTENT ; AMIDE ; SCALE
WOS研究方向	Chemistry
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000260703000005
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279435]
专题	药物化学研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Liu, Hong
作者单位	1.Chinese Acad Sci, Shanghai Inst Biol Sci, Grad Sch, Shanghai Inst Mat Med,Natl Ctr Drug Screening, Shanghai 201203, Peoples R China; 2.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Biol Sci, Grad Sch, Shanghai Inst Mat Med,State Key Lab Drug Res, Shanghai 201203, Peoples R China; 4.Shenyang Pharmaceut Univ, Sch Pharmaceut Engn, Shenyang 110016, Liaoning, Peoples R China;
推荐引用方式 GB/T 7714	Deng, Guanghui,Ye, Deju,Li, Yuanyuan,et al. Synthesis of (S)-, (R)-, and (rac)-2-amino-3,3-bis(4-fluorophenyl)propanoic acids and an evaluation of the DPP IV inhibitory activity of Denagliptin diastereomers[J]. TETRAHEDRON,2008,64(46):10512-10516.
APA	Deng, Guanghui.,Ye, Deju.,Li, Yuanyuan.,He, Lingyan.,Zhou, Yu.,...&Liu, Hong.(2008).Synthesis of (S)-, (R)-, and (rac)-2-amino-3,3-bis(4-fluorophenyl)propanoic acids and an evaluation of the DPP IV inhibitory activity of Denagliptin diastereomers.TETRAHEDRON,64(46),10512-10516.
MLA	Deng, Guanghui,et al."Synthesis of (S)-, (R)-, and (rac)-2-amino-3,3-bis(4-fluorophenyl)propanoic acids and an evaluation of the DPP IV inhibitory activity of Denagliptin diastereomers".TETRAHEDRON 64.46(2008):10512-10516.