N-Acetyl-l-phenylalanine Racemization during TBTU Amidation: An In-Depth Study for the Synthesis of Anti-Inflammatory 2-(N-Acetyl)-l-phenylalanylamido-2-deoxy-d-glucose (NAPA)

A thorough study on the amidation conditions of N-acetyl-l-phenylalanine using TBTU and various bases is reported for the synthesis of 2-(N-acetyl)-l-phenylalanylamido-2-deoxy-d-glucose (NAPA), a promising drug for the treatment of joints diseases. TBTU-mediated diastereoselective amidation reaction...

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Autores principales: Sturabotti, Elisa, Vetica, Fabrizio, Toscano, Giorgia, Calcaterra, Andrea, Martinelli, Andrea, Migneco, Luisa Maria, Leonelli, Francesca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9863357/
https://www.ncbi.nlm.nih.gov/pubmed/36677671
http://dx.doi.org/10.3390/molecules28020581
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author Sturabotti, Elisa
Vetica, Fabrizio
Toscano, Giorgia
Calcaterra, Andrea
Martinelli, Andrea
Migneco, Luisa Maria
Leonelli, Francesca
author_facet Sturabotti, Elisa
Vetica, Fabrizio
Toscano, Giorgia
Calcaterra, Andrea
Martinelli, Andrea
Migneco, Luisa Maria
Leonelli, Francesca
author_sort Sturabotti, Elisa
collection PubMed
description A thorough study on the amidation conditions of N-acetyl-l-phenylalanine using TBTU and various bases is reported for the synthesis of 2-(N-acetyl)-l-phenylalanylamido-2-deoxy-d-glucose (NAPA), a promising drug for the treatment of joints diseases. TBTU-mediated diastereoselective amidation reaction with 1,3,4,6-tetra-O-acetyl-β-d-glucosamine always gave racemization of N-acetyl-l-phenylalanine. The stereochemical retention under amidation conditions was studied in detail in the presence of difference bases and via other control experiments, evidencing the possibility to reduce racemization using pyridine as base.
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spelling pubmed-98633572023-01-22 N-Acetyl-l-phenylalanine Racemization during TBTU Amidation: An In-Depth Study for the Synthesis of Anti-Inflammatory 2-(N-Acetyl)-l-phenylalanylamido-2-deoxy-d-glucose (NAPA) Sturabotti, Elisa Vetica, Fabrizio Toscano, Giorgia Calcaterra, Andrea Martinelli, Andrea Migneco, Luisa Maria Leonelli, Francesca Molecules Article A thorough study on the amidation conditions of N-acetyl-l-phenylalanine using TBTU and various bases is reported for the synthesis of 2-(N-acetyl)-l-phenylalanylamido-2-deoxy-d-glucose (NAPA), a promising drug for the treatment of joints diseases. TBTU-mediated diastereoselective amidation reaction with 1,3,4,6-tetra-O-acetyl-β-d-glucosamine always gave racemization of N-acetyl-l-phenylalanine. The stereochemical retention under amidation conditions was studied in detail in the presence of difference bases and via other control experiments, evidencing the possibility to reduce racemization using pyridine as base. MDPI 2023-01-06 /pmc/articles/PMC9863357/ /pubmed/36677671 http://dx.doi.org/10.3390/molecules28020581 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sturabotti, Elisa
Vetica, Fabrizio
Toscano, Giorgia
Calcaterra, Andrea
Martinelli, Andrea
Migneco, Luisa Maria
Leonelli, Francesca
N-Acetyl-l-phenylalanine Racemization during TBTU Amidation: An In-Depth Study for the Synthesis of Anti-Inflammatory 2-(N-Acetyl)-l-phenylalanylamido-2-deoxy-d-glucose (NAPA)
title N-Acetyl-l-phenylalanine Racemization during TBTU Amidation: An In-Depth Study for the Synthesis of Anti-Inflammatory 2-(N-Acetyl)-l-phenylalanylamido-2-deoxy-d-glucose (NAPA)
title_full N-Acetyl-l-phenylalanine Racemization during TBTU Amidation: An In-Depth Study for the Synthesis of Anti-Inflammatory 2-(N-Acetyl)-l-phenylalanylamido-2-deoxy-d-glucose (NAPA)
title_fullStr N-Acetyl-l-phenylalanine Racemization during TBTU Amidation: An In-Depth Study for the Synthesis of Anti-Inflammatory 2-(N-Acetyl)-l-phenylalanylamido-2-deoxy-d-glucose (NAPA)
title_full_unstemmed N-Acetyl-l-phenylalanine Racemization during TBTU Amidation: An In-Depth Study for the Synthesis of Anti-Inflammatory 2-(N-Acetyl)-l-phenylalanylamido-2-deoxy-d-glucose (NAPA)
title_short N-Acetyl-l-phenylalanine Racemization during TBTU Amidation: An In-Depth Study for the Synthesis of Anti-Inflammatory 2-(N-Acetyl)-l-phenylalanylamido-2-deoxy-d-glucose (NAPA)
title_sort n-acetyl-l-phenylalanine racemization during tbtu amidation: an in-depth study for the synthesis of anti-inflammatory 2-(n-acetyl)-l-phenylalanylamido-2-deoxy-d-glucose (napa)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9863357/
https://www.ncbi.nlm.nih.gov/pubmed/36677671
http://dx.doi.org/10.3390/molecules28020581
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