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Article

Spiro β-Lactams as β-Turn Mimetics. Design, Synthesis, and NMR Conformational Analysis

Supporting Info

Eduardo Alonso,*^† Fernando López-Ortiz,^‡ Carlos del Pozo,^† Emma Peralta,^‡ Alberto Macías,^§ and Javier González*^†

Departamento de Qumica Orgnica e Inorgnica Universidad de Oviedo, 33071 Oviedo, Spain, rea de Qumica Orgnica, Universidad de Almera Carretera de Sacramento s/n 04120 Almera, Spain, and Qumica ID Asturias, SL c/Cat. Adolfo A. Buylla, 26, 33013 Oviedo, Spain

J. Org. Chem., 2001, 66 (19), pp 6333–6338

DOI: 10.1021/jo015714m

Publication Date (Web): August 24, 2001

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

†

Departamento de Química Orgánica e Inorgánica, Universidad de Oviedo, 33071 Oviedo, Spain.

‡

Área de Química Orgánica, Universidad de Almería, Carretera de Sacramento s/n 04120 Almería, Spain.

Química ID Asturias, SL c/Cat. Adolfo A. Buylla, 26, 33013 Oviedo, Spain.

, FJGF@sauron.quimica.uniovi.es

Abstract

Molecular modeling calculations using high-level ab initio methods (MP2/6-31+G*) of a new type of spiro β-lactams predict that these systems could adopt a β-turn secondary structure in solution. Strong intramolecular hydrogen bonds stabilize the β-turn conformation with a geometry that is very close to the ideal type II β-turns. The synthesis of the spiro β-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 β-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 β-turn conformation as predicted by the theoretical studies.

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