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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...

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Autores principales: Gao, Wenzheng, Han, Jiaxin, Greaves, Sophie, Harrity, Joseph P. A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
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.
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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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