Enhanced Stereoselectivity of a Cu(II) Complex Chiral Auxiliary in the Synthesis of Fmoc-L-γ-carboxyglutamic Acid

被引:14
|
作者
Smith, Daniel J. [1 ,2 ]
Yap, Glenn P. A. [2 ]
Kelley, James A. [1 ]
Schneider, Joel P. [1 ]
机构
[1] Natl Canc Inst Frederick, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA
[2] Univ Delaware, Dept Chem & Biochem, Newark, DE 19716 USA
来源
JOURNAL OF ORGANIC CHEMISTRY | 2011年 / 76卷 / 06期
关键词
MICHAEL ADDITION-REACTIONS; ALPHA-AMINO-ACIDS; SUBSTITUTED GLUTAMIC ACIDS; EFFICIENT ASYMMETRIC-SYNTHESIS; VIRTUALLY COMPLETE CONTROL; STEM-CELL DIFFERENTIATION; NI-II COMPLEXES; NUCLEOPHILIC GLYCINE; FACE DIASTEREOSELECTIVITY; PYROGLUTAMIC ACIDS;
D O I
10.1021/jo101940k
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
L-gamma-Carboxyglutamic acid (Gla) is an uncommon amino acid that binds avidly to mineral surfaces and metal ions. Herein, we report the synthesis of N-alpha-Fmoc-L-gamma-carboxyglutamic acid gamma,gamma'-tert-butyl ester (Fmoc-Gla(O(t)Bu)(2)-OH), a suitably protected analogue for Fmoc-based solid-phase peptide synthesis. The residue was synthesized using a novel chiral Cu(II) complex, whose structure-based design was inspired by the blue copper protein rusticyanin. The five-coordinate complex is formed by Shiff base formation between glycine and the novel ligand (S)-2-(N-(2-methylthio)benzylproly)aminobenzophenone in the presence of copper. Michael addition of di-tert-butyl methylenemalonate to the alpha-carbon of the glycine portion of the complex occurs in a diastereoselective fashion. The resulting (S,S)-complex diastereomer can be easily purified by chromatography. Metal complex decomposition followed by Fmoc protection affords the enantiomerically pure amino acid. With the use of this novel chiral complex, the asymmetric synthesis of Fmoc-Gla(O(t)Bu)(2)-OH was completed in nine steps from thiosalicylic acid in 14.5% overall yield.
引用
收藏
页码:1513 / 1520
页数:8
相关论文
共 50 条
  • [31] Chiral resolution of l- and d-alanine and a racemic macrocyclic nickel(II) complex: synthesis and crystal structures
    Ou, Guang-Chuan
    Li, Zhi-Zhang
    Zhang, Min
    Yuan, Xian-You
    TRANSITION METAL CHEMISTRY, 2014, 39 (02) : 135 - 140
  • [32] Chiral resolution of l- and d-alanine and a racemic macrocyclic nickel(II) complex: synthesis and crystal structures
    Guang-Chuan Ou
    Zhi-Zhang Li
    Min Zhang
    Xian-You Yuan
    Transition Metal Chemistry, 2014, 39 : 135 - 140
  • [33] An infinite chiral single-helical structure formed in Cu(II)-L-/D-glutamic acid system
    Mizutani, M
    Maejima, N
    Jitsukawa, K
    Masuda, H
    Einaga, H
    INORGANICA CHIMICA ACTA, 1998, 283 (01) : 105 - 110
  • [34] Synthesis, characterization, crystal structure and antimicrobial studies of a novel Cu(II) complex based on itaconic acid and nicotinamide
    Tella, Adedibu C.
    Owalude, Samson O.
    Ajibade, Peter A.
    Simon, Nzikahyel
    Olatunji, Sunday J.
    Abdelbaky, Mohammed S. M.
    Garcia-Granda, Santiago
    JOURNAL OF MOLECULAR STRUCTURE, 2016, 1125 : 570 - 575
  • [35] Synthesis, characterization, and biological activities of a Cu(II) complex with the non-steroidal antiinflammatory drug flufenamic acid
    Sheng, Gui-Hua
    Wang, Tian-Rui
    Wang, Cun-Fang
    Chen, Xiang-Fei
    Ma, Zheng
    Zhu, Hai-Liang
    Zhou, Quan-Cheng
    JOURNAL OF COORDINATION CHEMISTRY, 2017, 70 (20) : 3501 - 3512
  • [36] Synthesis, structure and stability of a chiral imine-based Schiff-based ligand derived from L-glutamic acid and its [Cu4] complex
    Muche, Simon
    Levacheva, Irina
    Samsonova, Olga
    Biernasiuk, Anna
    Maim, Anna
    Lonsdale, Richard
    Popiolek, Lukasz
    Bakowsky, Udo
    Holynska, Malgorzata
    JOURNAL OF MOLECULAR STRUCTURE, 2017, 1127 : 231 - 236
  • [37] Synthesis, structure and magnetic properties of four chiral Cu(II) complexes based on N-benzoyl-L-glutamic acid and different N-donor ancillary ligands
    Yan, Ming-Jie
    Feng, Qi
    Song, Hui-Hua
    Yu, Hai-Tao
    INORGANICA CHIMICA ACTA, 2016, 450 : 304 - 314
  • [38] Chiral Cu(II)-N4 Complex Catalyzed Asymmetric Aza-Henry Reaction and Its Application in the Synthesis of β-Diamine
    Menapara, Tusharkumar
    Tak, Rajkumar
    Chinnaraja, E.
    Kureshy, Rukhsana I.
    Patel, Parth
    Khan, Noor-ul H.
    CHEMISTRYSELECT, 2017, 2 (14): : 4063 - 4067
  • [39] Asymmetric Henry reaction catalyzed by a chiral Cu(II) complex: a facile enantioselective synthesis of (S)-2-nitro-1-arylethanols
    Reddy, Basi V. Subba
    Reddy, Sankham Madhusudana
    Manisha, Swain
    Madan, Chinnala
    TETRAHEDRON-ASYMMETRY, 2011, 22 (05) : 530 - 535
  • [40] Speciation Study of L-ascorbic Acid and its Chelated Cu(II) & Ni(II) Complexes: an Experimental and Theoretical Model of Complex Formation
    Mahata, Sujay
    Mitra, Ishani
    Mukherjee, Subhajit
    Reddy, Venkata Pera B.
    Ghosh, Goutam Kr
    Linert, Wolfgang
    Moi, Sankar Ch
    SOUTH AFRICAN JOURNAL OF CHEMISTRY-SUID-AFRIKAANSE TYDSKRIF VIR CHEMIE, 2019, 72 : 229 - +