Department of Chemistry and Industrial Chemistry, University of Genova via Dodecaneso, 31, 16146 Genova, Italy.
Chemistry. 2013 Apr 2;19(14):4563-9. doi: 10.1002/chem.201300023. Epub 2013 Feb 12.
A straightforward and fully stereoselective synthesis of a new class of peptidomimetics, that is α-oxo-γ-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 α-oxo-γ-acylaminoamides afforded α-hydroxy-γ-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.
一种新的肽模拟物，即α-氧代-γ-酰氨基酰胺，通过一系列反应从各种苯甲醛中直接、完全立体选择性合成。该序列包括：1）不对称有机催化曼尼希反应，2）Passerini 多组分反应，3）胺脱保护-酰基迁移，4）最后氧化。整个序列可以在不纯化中间体的情况下进行，代表了首例同型 Passerini-胺脱保护-酰基迁移（PADAM）策略。α-氧代-γ-酰氨基酰胺的高度立体选择性还原也得到了α-羟基-γ-酰氨基酰胺。在某些情况下，通过简单地改变还原剂可以得到两种非对映异构体。最后，从保护的水杨醛出发，经过相同的序列，再进行 Mitsunobu 环化反应，可以得到高取代的色满。
