Details

Autor(en) / Beteiligte

• Pecchini, Pietro
• Fochi, Mariafrancesca
• Bartoccini, Francesca
• Piersanti, Giovanni
• Bernardi, Luca

Titel

Enantioselective organocatalytic strategies to access noncanonical -amino acids

Ist Teil von

• Chemical science (Cambridge), 2024-04, Vol.15 (16), p.5832-5868

Erscheinungsjahr

2024

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Organocatalytic asymmetric synthesis has evolved over the years and continues to attract the interest of many researchers worldwide. Enantiopure noncanonical amino acids (ncAAs) are valuable building blocks in organic synthesis, medicinal chemistry, and chemical biology. They are employed in the elaboration of peptides and proteins with enhanced activities and/or improved properties compared to their natural counterparts, as chiral catalysts, in chiral ligand design, and as chiral building blocks for asymmetric syntheses of complex molecules, including natural products. The linkage of ncAA synthesis and enantioselective organocatalysis, the subject of this perspective, tries to imitate the natural biosynthetic process. Herein, we present contemporary and earlier developments in the field of organocatalytic activation of simple feedstock materials, providing potential ncAAs with diverse side chains, unique three-dimensional structures, and a high degree of functionality. These asymmetric organocatalytic strategies, useful for forging a wide range of CC, CH, and CN bonds and/or combinations thereof, vary from classical name reactions, such as Ugi, Strecker, and Mannich reactions, to the most advanced concepts such as deracemisation, transamination, and carbene NH insertion. Concurrently, we present some interesting mechanistic studies/models, providing information on the chirality transfer process. Finally, this perspective highlights, through the diversity of the amino acids (AAs) not selected by nature for protein incorporation, the most generic modes of activation, induction, and reactivity commonly used, such as chiral enamine, hydrogen bonding, Brnsted acids/bases, and phase-transfer organocatalysis, reflecting their increasingly important role in organic and applied chemistry. Asymmetric organocatalysis has acquired a prominent place in modern synthesis of noncanonical -amino acids (ncAAs), valuable structural elements in organic synthesis, chemical biology, and medicine.