Solid-Phase Synthesis of Amine/Carboxyl Substituted Prolines and Proline Homologues: Scope and Limitations
A solid-phase procedure is used to synthesize racemic peptidomimetics based on the fundamental peptide unit. The peptidomimetics are constructed around proline or proline homologues variably substituted at the amine and carbonyl sites. The procedure expands the diversity of substituted peptidomimeti...
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| Format: | Article |
| Language: | English |
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MDPI AG
2016-03-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/21/3/350 |
| _version_ | 1818468173864763392 |
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| author | Ziniu Zhou William L. Scott Martin J. O’Donnell |
| author_facet | Ziniu Zhou William L. Scott Martin J. O’Donnell |
| author_sort | Ziniu Zhou |
| collection | DOAJ |
| description | A solid-phase procedure is used to synthesize racemic peptidomimetics based on the fundamental peptide unit. The peptidomimetics are constructed around proline or proline homologues variably substituted at the amine and carbonyl sites. The procedure expands the diversity of substituted peptidomimetic molecules available to the Distributed Drug Discovery (D3) project. Using a BAL-based solid-phase synthetic sequence the proline or proline homologue subunit is both constructed and incorporated into the peptidomimetic by an α-alkylation, hydrolysis and intramolecular cyclization sequence. Further transformations on solid-phase provide access to a variety of piperazine derivatives representing a class of molecules known to exhibit central nervous system activity. The procedure works well with proline cores, but with larger six- and seven-membered ring homologues the nature of the carboxylic acid acylating the cyclic amine can lead to side reactions and result in poor overall yields. |
| first_indexed | 2024-04-13T21:10:00Z |
| format | Article |
| id | doaj.art-f5cbf746bf704763aadb346a94ff7b76 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-13T21:10:00Z |
| publishDate | 2016-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-f5cbf746bf704763aadb346a94ff7b762022-12-22T02:29:52ZengMDPI AGMolecules1420-30492016-03-0121335010.3390/molecules21030350molecules21030350Solid-Phase Synthesis of Amine/Carboxyl Substituted Prolines and Proline Homologues: Scope and LimitationsZiniu Zhou0William L. Scott1Martin J. O’Donnell2Department of Pharmaceutical Engineering, Zhejiang Pharmaceutical College, 888 Yinxian Avenue Eastern Section, Ningbo 315100, ChinaDepartment of Chemistry and Chemical Biology, Indiana University-Purdue University Indianapolis, 402 N. Blackford Street, Indianapolis, IN 46202, USADepartment of Chemistry and Chemical Biology, Indiana University-Purdue University Indianapolis, 402 N. Blackford Street, Indianapolis, IN 46202, USAA solid-phase procedure is used to synthesize racemic peptidomimetics based on the fundamental peptide unit. The peptidomimetics are constructed around proline or proline homologues variably substituted at the amine and carbonyl sites. The procedure expands the diversity of substituted peptidomimetic molecules available to the Distributed Drug Discovery (D3) project. Using a BAL-based solid-phase synthetic sequence the proline or proline homologue subunit is both constructed and incorporated into the peptidomimetic by an α-alkylation, hydrolysis and intramolecular cyclization sequence. Further transformations on solid-phase provide access to a variety of piperazine derivatives representing a class of molecules known to exhibit central nervous system activity. The procedure works well with proline cores, but with larger six- and seven-membered ring homologues the nature of the carboxylic acid acylating the cyclic amine can lead to side reactions and result in poor overall yields.http://www.mdpi.com/1420-3049/21/3/350proline and homologuespiperazine derivativespeptidomimeticssolid-phase organic synthesiscombinatorial chemistryDistributed Drug Discovery (D3)CNS agent. |
| spellingShingle | Ziniu Zhou William L. Scott Martin J. O’Donnell Solid-Phase Synthesis of Amine/Carboxyl Substituted Prolines and Proline Homologues: Scope and Limitations Molecules proline and homologues piperazine derivatives peptidomimetics solid-phase organic synthesis combinatorial chemistry Distributed Drug Discovery (D3) CNS agent. |
| title | Solid-Phase Synthesis of Amine/Carboxyl Substituted Prolines and Proline Homologues: Scope and Limitations |
| title_full | Solid-Phase Synthesis of Amine/Carboxyl Substituted Prolines and Proline Homologues: Scope and Limitations |
| title_fullStr | Solid-Phase Synthesis of Amine/Carboxyl Substituted Prolines and Proline Homologues: Scope and Limitations |
| title_full_unstemmed | Solid-Phase Synthesis of Amine/Carboxyl Substituted Prolines and Proline Homologues: Scope and Limitations |
| title_short | Solid-Phase Synthesis of Amine/Carboxyl Substituted Prolines and Proline Homologues: Scope and Limitations |
| title_sort | solid phase synthesis of amine carboxyl substituted prolines and proline homologues scope and limitations |
| topic | proline and homologues piperazine derivatives peptidomimetics solid-phase organic synthesis combinatorial chemistry Distributed Drug Discovery (D3) CNS agent. |
| url | http://www.mdpi.com/1420-3049/21/3/350 |
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