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
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