<i>N</i>-Acetyl-<span style="font-variant: small-caps">l</span>-phenylalanine Racemization during TBTU Amidation: An In-Depth Study for the Synthesis of Anti-Inflammatory 2-(<i>N</i>-Acetyl)-<span style="font-variant: small-caps">l</span>-phenylalanylamido-2-deoxy-<span style="font-variant: small-caps">d</span>-glucose (NAPA)
A thorough study on the amidation conditions of <i>N</i>-acetyl-<span style="font-variant: small-caps;">l</span>-phenylalanine using TBTU and various bases is reported for the synthesis of 2-(<i>N</i>-acetyl)-<span style="font-variant: small-caps...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-01-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/28/2/581 |
| _version_ | 1797438294221389824 |
|---|---|
| author | Elisa Sturabotti Fabrizio Vetica Giorgia Toscano Andrea Calcaterra Andrea Martinelli Luisa Maria Migneco Francesca Leonelli |
| author_facet | Elisa Sturabotti Fabrizio Vetica Giorgia Toscano Andrea Calcaterra Andrea Martinelli Luisa Maria Migneco Francesca Leonelli |
| author_sort | Elisa Sturabotti |
| collection | DOAJ |
| description | A thorough study on the amidation conditions of <i>N</i>-acetyl-<span style="font-variant: small-caps;">l</span>-phenylalanine using TBTU and various bases is reported for the synthesis of 2-(<i>N</i>-acetyl)-<span style="font-variant: small-caps;">l</span>-phenylalanylamido-2-deoxy-<span style="font-variant: small-caps;">d</span>-glucose (NAPA), a promising drug for the treatment of joints diseases. TBTU-mediated diastereoselective amidation reaction with 1,3,4,6-tetra-<i>O</i>-acetyl-β-<span style="font-variant: small-caps;">d</span>-glucosamine always gave racemization of <i>N</i>-acetyl-<span style="font-variant: small-caps;">l</span>-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. |
| first_indexed | 2024-03-09T11:35:35Z |
| format | Article |
| id | doaj.art-0ed5a066592844f4abf157a49bab78ec |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T11:35:35Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-0ed5a066592844f4abf157a49bab78ec2023-11-30T23:42:12ZengMDPI AGMolecules1420-30492023-01-0128258110.3390/molecules28020581<i>N</i>-Acetyl-<span style="font-variant: small-caps">l</span>-phenylalanine Racemization during TBTU Amidation: An In-Depth Study for the Synthesis of Anti-Inflammatory 2-(<i>N</i>-Acetyl)-<span style="font-variant: small-caps">l</span>-phenylalanylamido-2-deoxy-<span style="font-variant: small-caps">d</span>-glucose (NAPA)Elisa Sturabotti0Fabrizio Vetica1Giorgia Toscano2Andrea Calcaterra3Andrea Martinelli4Luisa Maria Migneco5Francesca Leonelli6Department of Chemistry, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, ItalyDepartment of Chemistry, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, ItalyDepartment of Chemistry, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, ItalyDepartment of Chemistry and Technology of Drugs, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, ItalyDepartment of Chemistry, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, ItalyDepartment of Chemistry, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, ItalyDepartment of Chemistry, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, ItalyA thorough study on the amidation conditions of <i>N</i>-acetyl-<span style="font-variant: small-caps;">l</span>-phenylalanine using TBTU and various bases is reported for the synthesis of 2-(<i>N</i>-acetyl)-<span style="font-variant: small-caps;">l</span>-phenylalanylamido-2-deoxy-<span style="font-variant: small-caps;">d</span>-glucose (NAPA), a promising drug for the treatment of joints diseases. TBTU-mediated diastereoselective amidation reaction with 1,3,4,6-tetra-<i>O</i>-acetyl-β-<span style="font-variant: small-caps;">d</span>-glucosamine always gave racemization of <i>N</i>-acetyl-<span style="font-variant: small-caps;">l</span>-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.https://www.mdpi.com/1420-3049/28/2/581racemization<i>N</i>-acetyl amino acidscouplingTBTUpyridine |
| spellingShingle | Elisa Sturabotti Fabrizio Vetica Giorgia Toscano Andrea Calcaterra Andrea Martinelli Luisa Maria Migneco Francesca Leonelli <i>N</i>-Acetyl-<span style="font-variant: small-caps">l</span>-phenylalanine Racemization during TBTU Amidation: An In-Depth Study for the Synthesis of Anti-Inflammatory 2-(<i>N</i>-Acetyl)-<span style="font-variant: small-caps">l</span>-phenylalanylamido-2-deoxy-<span style="font-variant: small-caps">d</span>-glucose (NAPA) Molecules racemization <i>N</i>-acetyl amino acids coupling TBTU pyridine |
| title | <i>N</i>-Acetyl-<span style="font-variant: small-caps">l</span>-phenylalanine Racemization during TBTU Amidation: An In-Depth Study for the Synthesis of Anti-Inflammatory 2-(<i>N</i>-Acetyl)-<span style="font-variant: small-caps">l</span>-phenylalanylamido-2-deoxy-<span style="font-variant: small-caps">d</span>-glucose (NAPA) |
| title_full | <i>N</i>-Acetyl-<span style="font-variant: small-caps">l</span>-phenylalanine Racemization during TBTU Amidation: An In-Depth Study for the Synthesis of Anti-Inflammatory 2-(<i>N</i>-Acetyl)-<span style="font-variant: small-caps">l</span>-phenylalanylamido-2-deoxy-<span style="font-variant: small-caps">d</span>-glucose (NAPA) |
| title_fullStr | <i>N</i>-Acetyl-<span style="font-variant: small-caps">l</span>-phenylalanine Racemization during TBTU Amidation: An In-Depth Study for the Synthesis of Anti-Inflammatory 2-(<i>N</i>-Acetyl)-<span style="font-variant: small-caps">l</span>-phenylalanylamido-2-deoxy-<span style="font-variant: small-caps">d</span>-glucose (NAPA) |
| title_full_unstemmed | <i>N</i>-Acetyl-<span style="font-variant: small-caps">l</span>-phenylalanine Racemization during TBTU Amidation: An In-Depth Study for the Synthesis of Anti-Inflammatory 2-(<i>N</i>-Acetyl)-<span style="font-variant: small-caps">l</span>-phenylalanylamido-2-deoxy-<span style="font-variant: small-caps">d</span>-glucose (NAPA) |
| title_short | <i>N</i>-Acetyl-<span style="font-variant: small-caps">l</span>-phenylalanine Racemization during TBTU Amidation: An In-Depth Study for the Synthesis of Anti-Inflammatory 2-(<i>N</i>-Acetyl)-<span style="font-variant: small-caps">l</span>-phenylalanylamido-2-deoxy-<span style="font-variant: small-caps">d</span>-glucose (NAPA) |
| title_sort | i n i acetyl span style font variant small caps l span phenylalanine racemization during tbtu amidation an in depth study for the synthesis of anti inflammatory 2 i n i acetyl span style font variant small caps l span phenylalanylamido 2 deoxy span style font variant small caps d span glucose napa |
| topic | racemization <i>N</i>-acetyl amino acids coupling TBTU pyridine |
| url | https://www.mdpi.com/1420-3049/28/2/581 |
| work_keys_str_mv | AT elisasturabotti iniacetylspanstylefontvariantsmallcapslspanphenylalanineracemizationduringtbtuamidationanindepthstudyforthesynthesisofantiinflammatory2iniacetylspanstylefontvariantsmallcapslspanphenylalanylamido2deoxyspanstylefontvariantsmallcapsdspanglucosenapa AT fabriziovetica iniacetylspanstylefontvariantsmallcapslspanphenylalanineracemizationduringtbtuamidationanindepthstudyforthesynthesisofantiinflammatory2iniacetylspanstylefontvariantsmallcapslspanphenylalanylamido2deoxyspanstylefontvariantsmallcapsdspanglucosenapa AT giorgiatoscano iniacetylspanstylefontvariantsmallcapslspanphenylalanineracemizationduringtbtuamidationanindepthstudyforthesynthesisofantiinflammatory2iniacetylspanstylefontvariantsmallcapslspanphenylalanylamido2deoxyspanstylefontvariantsmallcapsdspanglucosenapa AT andreacalcaterra iniacetylspanstylefontvariantsmallcapslspanphenylalanineracemizationduringtbtuamidationanindepthstudyforthesynthesisofantiinflammatory2iniacetylspanstylefontvariantsmallcapslspanphenylalanylamido2deoxyspanstylefontvariantsmallcapsdspanglucosenapa AT andreamartinelli iniacetylspanstylefontvariantsmallcapslspanphenylalanineracemizationduringtbtuamidationanindepthstudyforthesynthesisofantiinflammatory2iniacetylspanstylefontvariantsmallcapslspanphenylalanylamido2deoxyspanstylefontvariantsmallcapsdspanglucosenapa AT luisamariamigneco iniacetylspanstylefontvariantsmallcapslspanphenylalanineracemizationduringtbtuamidationanindepthstudyforthesynthesisofantiinflammatory2iniacetylspanstylefontvariantsmallcapslspanphenylalanylamido2deoxyspanstylefontvariantsmallcapsdspanglucosenapa AT francescaleonelli iniacetylspanstylefontvariantsmallcapslspanphenylalanineracemizationduringtbtuamidationanindepthstudyforthesynthesisofantiinflammatory2iniacetylspanstylefontvariantsmallcapslspanphenylalanylamido2deoxyspanstylefontvariantsmallcapsdspanglucosenapa |