Enantioselective organocatalytic strategies to access noncanonical α-amino acids
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 ela...
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| Published in | Chemical science (Cambridge) Vol. 15; no. 16; pp. 5832 - 5868 |
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| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
Royal Society of Chemistry
24.04.2024
The Royal Society of Chemistry |
| Subjects | |
| Online Access | Get full text |
| ISSN | 2041-6520 2041-6539 |
| DOI | 10.1039/d4sc01081g |
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| Summary: | 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 C-C, C-H, and C-N 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 N-H 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, Brønsted 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 α-amino acids (ncAAs), valuable structural elements in organic synthesis, chemical biology, and medicine. |
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| Bibliography: | Luca Bernardi is currently associate professor at the University of Bologna, Italy, where he received an MSc in Industrial Chemistry in 2000, and PhD in 2004 (with Prof. A. Ricci). He was a post-doc in Aarhus (Denmark) and a visiting scientist in Groningen (The Netherlands). His research interests focus mainly on enantioselective organocatalysis, and on the valorisation of biopolymers from marine sources. He has been involved in several industrial activities and is serving as coordinator of the national PRIN2020 project "Natural products-assisted organic synthesis". Pietro Pecchini received his M.Sc. in Chemistry from the University of Bologna in 2022. During the master thesis internship with Prof. L. Bernardi, he worked on stabilized sulfoxonium ylides in aminocatalysis for enantioselective cyclopropanations. Currently, he is spending his second year of PhD in the Bernardi/Fochi group, focusing on sulfoxonium ylide reactivity in organocatalysis and heterogeneous asymmetric catalysis based on the exploitation of gels derived from renewable alginate biopolymers. Mariafrancesca Fochi received her master's degree in 1994 and PhD in Chemistry in 1998 from the University of Bologna with Prof. A. Ricci. She spent research periods as an academic visitor at the University of Nijmegen (The Netherlands) and at Oxford University (UK). In 2004, she was appointed assistant professor, and in 2019 associate professor, at the University of Bologna. Her scientific interests include acylsilane and thioacylsilane chemistry, chiral ferrocene derivatives, metal-mediated homogeneous asymmetric catalysis and finally asymmetric organocatalysis. She is a co-author of more than 80 papers published in international journals. Francesca Bartoccini received her master's degree in chemistry in 2001 from the University of Bologna under the supervision of Prof. Gianfranco Cainelli. She then moved to the University of Urbino Carlo Bo to join Prof. Giorgio Tarzia's research group. Since 2003, she has been working as a laboratory technician at the same University. In 2020, she was awarded with the National Scientific Habilitation as Associate Professor of Organic Chemistry. Her research interests include dehydroamino acids, organic compounds containing boron, non-canonical amino acids, natural products, and (bio)molecules with redox-active sulfhydryl function(s). In 2017, she co-founded the academic spin-off GLUOS srl. Giovanni Piersanti received his MS in Chemistry from the University of Bologna. He moved to the University of Urbino Carlo Bo, where he got his PhD. After a period at the University of California-Berkeley, Massachusetts Institute of Technology and Nerviano Medical Sciences, he returned to Urbino in 2006 to begin his independent career where he has remained since and is now Full Professor. His current research focus is on the synthesis of noncanonical amino acids/peptides and natural products in concert with the discovery and the development of new transformations including catalytic, asymmetric, practical and green processes. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Review-3 content type line 23 |
| ISSN: | 2041-6520 2041-6539 |
| DOI: | 10.1039/d4sc01081g |