Solid supported high-throughput organic synthesis of peptide β-turn mimetics via Petasis reaction/diketopiperazine formation

被引:54
作者
Golebiowski, A [1 ]
Klopfenstein, SR [1 ]
Chen, JJ [1 ]
Shao, X [1 ]
机构
[1] Proctor & Gamble Pharmaceut, Combinatorial Chem Grp, Hlth Care Res Ctr, Mason, OH 45040 USA
关键词
solid-phase synthesis; Petasis reaction; peptide beta-turn mimetics; combinatorial chemistry; bicyclic heterocyclic compounds;
D O I
10.1016/S0040-4039(00)00669-9
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
High-throughput organic synthesis of bicyclic diketopiperazines 1, beta-turn mimetics, is described. Starting from Merrifield resin-bound piperazine-2-carboxylic acid, first two (R-4 and R-5) Side chains are introduced via the Petasis reaction and subsequent amide bond formation. Unblocking the a-amino group of piperazine-2-carboxylic acid, Boc-N-protected alpha-amino acid coupling and deprotection followed by cyclative cleavage introduces the remaining R-2 and R-1 side chains. (C) 2000 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:4841 / 4844
页数:4
相关论文
共 12 条
  • [1] PEPTIDOMIMETICS FOR RECEPTOR LIGANDS DISCOVERY, DEVELOPMENT, AND MEDICAL PERSPECTIVES
    GIANNIS, A
    [J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 1993, 32 (09) : 1244 - 1267
  • [2] Gillespie P, 1997, BIOPOLYMERS, V43, P191, DOI 10.1002/(SICI)1097-0282(1997)43:3<191::AID-BIP2>3.3.CO
  • [3] 2-2
  • [4] Rationally designed non-peptides: Variously substituted piperazine libraries for the discovery of bradykinin antagonists and other G-protein-coupled receptor ligands
    Goodfellow, VS
    Laudeman, CP
    Gerrity, JI
    Burkard, M
    Strobel, E
    Zuzack, JS
    McLeod, DA
    [J]. MOLECULAR DIVERSITY, 1996, 2 (1-2) : 97 - 102
  • [5] Design and synthesis of conformationally constrained amino acids as versatile scaffolds and peptide mimetics
    Hanessian, S
    McNaughtonSmith, G
    Lombart, HG
    Lubell, WD
    [J]. TETRAHEDRON, 1997, 53 (38) : 12789 - 12854
  • [6] KAHN M, 1993, SYNLETT, P821
  • [7] A practical synthesis of peptide mimetics via the solid-phase Petasis reaction
    Klopfenstein, SR
    Chen, JJ
    Golebiowski, A
    Li, M
    Peng, SX
    Shao, X
    [J]. TETRAHEDRON LETTERS, 2000, 41 (25) : 4835 - 4839
  • [8] MAARSEVEEN JH, 1998, COMB CHEM HIGH T SCR, V1, P185
  • [9] THE BORONIC ACID MANNICH REACTION - A NEW METHOD FOR THE SYNTHESIS OF GEOMETRICALLY PURE ALLYLAMINES
    PETASIS, NA
    AKRITOPOULOU, I
    [J]. TETRAHEDRON LETTERS, 1993, 34 (04) : 583 - 586
  • [10] TURNS IN PEPTIDES AND PROTEINS
    ROSE, GD
    GIERASCH, LM
    SMITH, JA
    [J]. ADVANCES IN PROTEIN CHEMISTRY, 1985, 37 : 1 - 109