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Asymmetric Synthesis of Functionalizable Type II β-Turn-Inducing α-Amino Acid Building Blocks
[Image: see text] Peptidomimetics are emerging as a promising class of potent and selective therapeutics. Among the current approaches to these compounds, the utilization of constrained lactams is a key element in enforcing the active peptide conformation, and the development of efficient and stereo...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10496131/ https://www.ncbi.nlm.nih.gov/pubmed/37642309 http://dx.doi.org/10.1021/acs.orglett.3c02376 |
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author | Gao, Wenzheng Han, Jiaxin Greaves, Sophie Harrity, Joseph P. A. |
author_facet | Gao, Wenzheng Han, Jiaxin Greaves, Sophie Harrity, Joseph P. A. |
author_sort | Gao, Wenzheng |
collection | PubMed |
description | [Image: see text] Peptidomimetics are emerging as a promising class of potent and selective therapeutics. Among the current approaches to these compounds, the utilization of constrained lactams is a key element in enforcing the active peptide conformation, and the development of efficient and stereocontrolled methods for generating such lactam building blocks is an important objective. Current methods typically rely on the elaboration of existing α-amino acids, and in so doing, the side chain is sacrificed during the ring-forming process. We report a new asymmetric approach to lactam-constrained α-amino acid building blocks bearing a range of polar and hydrophobic side chains. The chemistry is amenable to rapidly generating di- and tripeptides, and the potential for these lactams to stabilize type II β-turns is demonstrated in the synthesis of the melanocyte-inhibiting factor peptidomimetic. |
format | Online Article Text |
id | pubmed-10496131 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-104961312023-09-13 Asymmetric Synthesis of Functionalizable Type II β-Turn-Inducing α-Amino Acid Building Blocks Gao, Wenzheng Han, Jiaxin Greaves, Sophie Harrity, Joseph P. A. Org Lett [Image: see text] Peptidomimetics are emerging as a promising class of potent and selective therapeutics. Among the current approaches to these compounds, the utilization of constrained lactams is a key element in enforcing the active peptide conformation, and the development of efficient and stereocontrolled methods for generating such lactam building blocks is an important objective. Current methods typically rely on the elaboration of existing α-amino acids, and in so doing, the side chain is sacrificed during the ring-forming process. We report a new asymmetric approach to lactam-constrained α-amino acid building blocks bearing a range of polar and hydrophobic side chains. The chemistry is amenable to rapidly generating di- and tripeptides, and the potential for these lactams to stabilize type II β-turns is demonstrated in the synthesis of the melanocyte-inhibiting factor peptidomimetic. American Chemical Society 2023-08-29 /pmc/articles/PMC10496131/ /pubmed/37642309 http://dx.doi.org/10.1021/acs.orglett.3c02376 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Gao, Wenzheng Han, Jiaxin Greaves, Sophie Harrity, Joseph P. A. Asymmetric Synthesis of Functionalizable Type II β-Turn-Inducing α-Amino Acid Building Blocks |
title | Asymmetric Synthesis of Functionalizable Type II β-Turn-Inducing
α-Amino Acid Building Blocks |
title_full | Asymmetric Synthesis of Functionalizable Type II β-Turn-Inducing
α-Amino Acid Building Blocks |
title_fullStr | Asymmetric Synthesis of Functionalizable Type II β-Turn-Inducing
α-Amino Acid Building Blocks |
title_full_unstemmed | Asymmetric Synthesis of Functionalizable Type II β-Turn-Inducing
α-Amino Acid Building Blocks |
title_short | Asymmetric Synthesis of Functionalizable Type II β-Turn-Inducing
α-Amino Acid Building Blocks |
title_sort | asymmetric synthesis of functionalizable type ii β-turn-inducing
α-amino acid building blocks |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10496131/ https://www.ncbi.nlm.nih.gov/pubmed/37642309 http://dx.doi.org/10.1021/acs.orglett.3c02376 |
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