A straightforward and fully stereoselective synthesis of a new class of peptidomimetics, that is alpha-oxo-gamma-acylaminoamides, was achieved starting from various benzaldehydes by a sequence of 1) an asymmetric organocatalytic Mannich reaction, 2) a Passerini multicomponent reaction, 3) an amine deprotection–acyl migration protocol, and 4) a final oxidation. The whole sequence can be performed without purification of the intermediates and represents the first example of a homo-Passerini– amine deprotection–acyl migration (PADAM) strategy. Highly stereoselective reduction of the alpha-oxo-gamma-acylaminoamides afforded alpha-hydroxy-gamma-acylaminoamides as well. In some cases both diastereomers were obtained by simply changing the reducing agent. Finally, starting from protected salicylaldehyde, the same sequence, followed by a Mitsunobu cyclization, afforded highly substituted chromanes.

The homo-PADAM Protocol: Stereoselective and Operationally Simple Synthesis of alpha-Oxo or alpha-Hydroxy-gamma-acylaminoamides and Chromanes

MORANA, FABIO;BASSO, ANDREA;ROCCA, VALERIA MARISA;RIVA, RENATA;BANFI, LUCA
2013

Abstract

A straightforward and fully stereoselective synthesis of a new class of peptidomimetics, that is alpha-oxo-gamma-acylaminoamides, was achieved starting from various benzaldehydes by a sequence of 1) an asymmetric organocatalytic Mannich reaction, 2) a Passerini multicomponent reaction, 3) an amine deprotection–acyl migration protocol, and 4) a final oxidation. The whole sequence can be performed without purification of the intermediates and represents the first example of a homo-Passerini– amine deprotection–acyl migration (PADAM) strategy. Highly stereoselective reduction of the alpha-oxo-gamma-acylaminoamides afforded alpha-hydroxy-gamma-acylaminoamides as well. In some cases both diastereomers were obtained by simply changing the reducing agent. Finally, starting from protected salicylaldehyde, the same sequence, followed by a Mitsunobu cyclization, afforded highly substituted chromanes.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11567/631175
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