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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Spiro beta-lactams as beta-turn mimetics. Design, synthesis, and NMR conformational analysis
E Alonso1, F López-Ortiz, C del Pozo
1Departamento de Química Orgánica e Inorgánica Universidad de Oviedo, 33071 Oviedo, Spain.
Abstract:
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 beta-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.
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