Enantiomeric Resolution and Absolute Configuration of a Chiral δ-Lactam, Useful Intermediate for the Synthesis of Bioactive Compounds
During the past several years, the frequency of discovery of new molecular entities based on γ- or δ-lactam scaffolds has increased continuously. Most of them are characterized by the presence of at least one chiral center. Herein, we present the preparation, isolation and the absolute configuration...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-12-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/25/24/6023 |
| _version_ | 1797544142414282752 |
|---|---|
| author | Roberta Listro Giacomo Rossino Serena Della Volpe Rita Stabile Massimo Boiocchi Lorenzo Malavasi Daniela Rossi Simona Collina |
| author_facet | Roberta Listro Giacomo Rossino Serena Della Volpe Rita Stabile Massimo Boiocchi Lorenzo Malavasi Daniela Rossi Simona Collina |
| author_sort | Roberta Listro |
| collection | DOAJ |
| description | During the past several years, the frequency of discovery of new molecular entities based on γ- or δ-lactam scaffolds has increased continuously. Most of them are characterized by the presence of at least one chiral center. Herein, we present the preparation, isolation and the absolute configuration assignment of enantiomeric 2-(4-bromophenyl)-1-isobutyl-6-oxopiperidin-3-carboxylic acid (<i>trans</i>-<b>1</b>). For the preparation of racemic <i>trans</i>-<b>1</b>, the Castagnoli-Cushman reaction was employed. (Semi)-preparative enantioselective HPLC allowed to obtain enantiomerically pure <i>trans</i>-<b>1</b> whose absolute configuration was assigned by X-ray diffractometry. Compound (+)-(<i>2R,3R</i>)-<b>1</b> represents a reference compound for the configurational study of structurally related lactams. |
| first_indexed | 2024-03-10T13:56:11Z |
| format | Article |
| id | doaj.art-6af4b1389d5e4d7d9ceaf74a87f7d14a |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T13:56:11Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-6af4b1389d5e4d7d9ceaf74a87f7d14a2023-11-21T01:37:55ZengMDPI AGMolecules1420-30492020-12-012524602310.3390/molecules25246023Enantiomeric Resolution and Absolute Configuration of a Chiral δ-Lactam, Useful Intermediate for the Synthesis of Bioactive CompoundsRoberta Listro0Giacomo Rossino1Serena Della Volpe2Rita Stabile3Massimo Boiocchi4Lorenzo Malavasi5Daniela Rossi6Simona Collina7Department of Drug Sciences, University of Pavia, via Taramelli 12, 27100 Pavia, ItalyDepartment of Drug Sciences, University of Pavia, via Taramelli 12, 27100 Pavia, ItalyDepartment of Drug Sciences, University of Pavia, via Taramelli 12, 27100 Pavia, ItalyDepartment of Drug Sciences, University of Pavia, via Taramelli 12, 27100 Pavia, ItalyCentro Grandi Strumenti, University of Pavia, via Bassi 21, 27100 Pavia, ItalyDepartment of Chemistry, University of Pavia, via Taramelli 12, 27100 Pavia, ItalyDepartment of Drug Sciences, University of Pavia, via Taramelli 12, 27100 Pavia, ItalyDepartment of Drug Sciences, University of Pavia, via Taramelli 12, 27100 Pavia, ItalyDuring the past several years, the frequency of discovery of new molecular entities based on γ- or δ-lactam scaffolds has increased continuously. Most of them are characterized by the presence of at least one chiral center. Herein, we present the preparation, isolation and the absolute configuration assignment of enantiomeric 2-(4-bromophenyl)-1-isobutyl-6-oxopiperidin-3-carboxylic acid (<i>trans</i>-<b>1</b>). For the preparation of racemic <i>trans</i>-<b>1</b>, the Castagnoli-Cushman reaction was employed. (Semi)-preparative enantioselective HPLC allowed to obtain enantiomerically pure <i>trans</i>-<b>1</b> whose absolute configuration was assigned by X-ray diffractometry. Compound (+)-(<i>2R,3R</i>)-<b>1</b> represents a reference compound for the configurational study of structurally related lactams.https://www.mdpi.com/1420-3049/25/24/6023lactam scaffoldenantioselective HPLCchiral resolutionX-ray diffractionabsolute configuration assignment |
| spellingShingle | Roberta Listro Giacomo Rossino Serena Della Volpe Rita Stabile Massimo Boiocchi Lorenzo Malavasi Daniela Rossi Simona Collina Enantiomeric Resolution and Absolute Configuration of a Chiral δ-Lactam, Useful Intermediate for the Synthesis of Bioactive Compounds Molecules lactam scaffold enantioselective HPLC chiral resolution X-ray diffraction absolute configuration assignment |
| title | Enantiomeric Resolution and Absolute Configuration of a Chiral δ-Lactam, Useful Intermediate for the Synthesis of Bioactive Compounds |
| title_full | Enantiomeric Resolution and Absolute Configuration of a Chiral δ-Lactam, Useful Intermediate for the Synthesis of Bioactive Compounds |
| title_fullStr | Enantiomeric Resolution and Absolute Configuration of a Chiral δ-Lactam, Useful Intermediate for the Synthesis of Bioactive Compounds |
| title_full_unstemmed | Enantiomeric Resolution and Absolute Configuration of a Chiral δ-Lactam, Useful Intermediate for the Synthesis of Bioactive Compounds |
| title_short | Enantiomeric Resolution and Absolute Configuration of a Chiral δ-Lactam, Useful Intermediate for the Synthesis of Bioactive Compounds |
| title_sort | enantiomeric resolution and absolute configuration of a chiral δ lactam useful intermediate for the synthesis of bioactive compounds |
| topic | lactam scaffold enantioselective HPLC chiral resolution X-ray diffraction absolute configuration assignment |
| url | https://www.mdpi.com/1420-3049/25/24/6023 |
| work_keys_str_mv | AT robertalistro enantiomericresolutionandabsoluteconfigurationofachiraldlactamusefulintermediateforthesynthesisofbioactivecompounds AT giacomorossino enantiomericresolutionandabsoluteconfigurationofachiraldlactamusefulintermediateforthesynthesisofbioactivecompounds AT serenadellavolpe enantiomericresolutionandabsoluteconfigurationofachiraldlactamusefulintermediateforthesynthesisofbioactivecompounds AT ritastabile enantiomericresolutionandabsoluteconfigurationofachiraldlactamusefulintermediateforthesynthesisofbioactivecompounds AT massimoboiocchi enantiomericresolutionandabsoluteconfigurationofachiraldlactamusefulintermediateforthesynthesisofbioactivecompounds AT lorenzomalavasi enantiomericresolutionandabsoluteconfigurationofachiraldlactamusefulintermediateforthesynthesisofbioactivecompounds AT danielarossi enantiomericresolutionandabsoluteconfigurationofachiraldlactamusefulintermediateforthesynthesisofbioactivecompounds AT simonacollina enantiomericresolutionandabsoluteconfigurationofachiraldlactamusefulintermediateforthesynthesisofbioactivecompounds |