Spiro β-lactams as β-turn mimetics.: Design, synthesis, and NMR conformational analysis

被引:106
作者
Alonso, E [1 ]
López-Ortiz, F
del Pozo, C
Peralta, E
Macías, A
González, J
机构
[1] Univ Oviedo, Dept Quim Organ & Inorgan, E-33071 Oviedo, Spain
[2] Univ Almeria, Area Quim Organ, Almeria 04120, Spain
[3] Quim ID Asturias, Oviedo 33013, Spain
关键词
D O I
10.1021/jo015714m
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
Molecular modeling calculations using high-level ab initio methods (MP2/6-31+G*) of a new type of spiro beta -lactams predict that these systems could adopt a beta -turn secondary structure in solution. Strong intramolecular hydrogen bonds stabilize the U-turn conformation with a geometry that is very close to the ideal type II beta -turns. The synthesis of the spiro beta -lactams is achieved by Staudinger reaction of a cyclic ketene derived from N-bencyloxycarbonyl-L-proline acid chloride with an imine. This reaction allows the formation of the spiranic backbone in a single-step with high diastereoselectivity and good yields. The new spiro beta -lactams obtained are the core for the preparation of different types of peptidomimetics using well-established peptide chemistry. The NMR conformational analysis shows that these compounds adopt beta -turn conformation as predicted by the theoretical studies.
引用
收藏
页码:6333 / 6338
页数:6
相关论文
共 23 条
  • [11] Horstmann TE, 2000, ANGEW CHEM INT EDIT, V39, P3635, DOI 10.1002/1521-3773(20001016)39:20<3635::AID-ANIE3635>3.0.CO
  • [12] 2-Y
  • [13] Design, synthesis, and dopamine receptor modulating activity of spiro bicyclic peptidomimetics of L-prolyl-L-leucyl-glycinamide
    Khalil, EM
    Ojala, WH
    Pradhan, A
    Nair, VD
    Gleason, WB
    Mishra, RK
    Johnson, RL
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (04) : 628 - 637
  • [14] CONFORMATIONS OF CYCLIC PEPTIDES .3. CYCLOPENTAGLYCYLTYROSYL AND RELATED COMPOUNDS
    KOPPLE, KD
    OHNISHI, M
    GO, A
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1969, 91 (15) : 4264 - +
  • [15] Kinetic resolution of alcohols catalyzed by tripeptides containing the N-alkylimidazole substructure
    Miller, SJ
    Copeland, GT
    Papaioannou, N
    Horstmann, TE
    Ruel, EM
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1998, 120 (07) : 1629 - 1630
  • [16] Müller G, 2000, ANGEW CHEM INT EDIT, V39, P894
  • [17] Palomo C, 1999, ANGEW CHEM INT EDIT, V38, P3056, DOI 10.1002/(SICI)1521-3773(19991018)38:20<3056::AID-ANIE3056>3.0.CO
  • [18] 2-J
  • [19] PROTON MAGNETIC-RESONANCE STUDIES IN TRIFLUOROETHANOL - SOLVENT MIXTURES AS A MEANS OF DELINEATING PEPTIDE PROTONS
    PITNER, TP
    URRY, DW
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1972, 94 (04) : 1399 - &
  • [20] Robinson J.A., 1999, SYNLETT, V4, P429