Diastereoselective Synthesis of (–)-Bestatin, Epibestatin, Phebestin and (3S,4R)-4-Amino-3-hydroxy-5-phenylpentanoic Acid from an Aldehyde Derived from d-Phenylalanine
Abstract A convenient and efficient method for the synthesis of (–)-bestatin, epibestatin, phebestin, and (3S,4R)-4-amino-3-hydroxy-5-phenylpentanoic acid is reported. The key step is a proline-catalyzed α-hydroxylation of an aldehyde derived from d-phenylalanine, which leads to incorporation of a h...
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| Format: | Article |
| Language: | English |
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Georg Thieme Verlag KG
2019-10-01
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| Series: | SynOpen |
| Subjects: | |
| Online Access: | http://www.thieme-connect.de/DOI/DOI?10.1055/s-0039-1690223 |
| _version_ | 1818260087092805632 |
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| author | Vipin Kumar Jain |
| author_facet | Vipin Kumar Jain |
| author_sort | Vipin Kumar Jain |
| collection | DOAJ |
| description | Abstract
A convenient and efficient method for the synthesis of (–)-bestatin, epibestatin, phebestin, and (3S,4R)-4-amino-3-hydroxy-5-phenylpentanoic acid is reported. The key step is a proline-catalyzed α-hydroxylation of an aldehyde derived from d-phenylalanine, which leads to incorporation of a hydroxyl group at the α-position of that aldehyde with good yield and very high diastereoselectivity. Bestatin and its diastereomer epibestatin are synthesized from the same starting material using the same sequence of reactions, except for proline as the catalyst. An O-MOM and Boc-protected amino acid, a common intermediate for bestatin, was coupled with a dipeptide, H-Val-Phe-OMe followed by global deprotection to yield phebestin. (3S,4R)-4-Amino-3-hydroxy-5-phenylpentanoic acid was also synthesized in eight steps from the same starting material. The reported synthetic route offers a general method for the synthesis of such types of compounds and their analogues by changing the proline catalyst and/or the starting material from d- to l-phenylalanine. |
| first_indexed | 2024-12-12T18:25:45Z |
| format | Article |
| id | doaj.art-d1730fd987054bc084047bbadb00ecec |
| institution | Directory Open Access Journal |
| issn | 2509-9396 |
| language | English |
| last_indexed | 2024-12-12T18:25:45Z |
| publishDate | 2019-10-01 |
| publisher | Georg Thieme Verlag KG |
| record_format | Article |
| series | SynOpen |
| spelling | doaj.art-d1730fd987054bc084047bbadb00ecec2022-12-22T00:16:01ZengGeorg Thieme Verlag KGSynOpen2509-93962019-10-01030411412310.1055/s-0039-1690223Diastereoselective Synthesis of (–)-Bestatin, Epibestatin, Phebestin and (3S,4R)-4-Amino-3-hydroxy-5-phenylpentanoic Acid from an Aldehyde Derived from d-PhenylalanineVipin Kumar Jain0Department of Chemistry, Indian Institute of Technology KanpurAbstract A convenient and efficient method for the synthesis of (–)-bestatin, epibestatin, phebestin, and (3S,4R)-4-amino-3-hydroxy-5-phenylpentanoic acid is reported. The key step is a proline-catalyzed α-hydroxylation of an aldehyde derived from d-phenylalanine, which leads to incorporation of a hydroxyl group at the α-position of that aldehyde with good yield and very high diastereoselectivity. Bestatin and its diastereomer epibestatin are synthesized from the same starting material using the same sequence of reactions, except for proline as the catalyst. An O-MOM and Boc-protected amino acid, a common intermediate for bestatin, was coupled with a dipeptide, H-Val-Phe-OMe followed by global deprotection to yield phebestin. (3S,4R)-4-Amino-3-hydroxy-5-phenylpentanoic acid was also synthesized in eight steps from the same starting material. The reported synthetic route offers a general method for the synthesis of such types of compounds and their analogues by changing the proline catalyst and/or the starting material from d- to l-phenylalanine.http://www.thieme-connect.de/DOI/DOI?10.1055/s-0039-1690223asymmetric hydroxylationorganocatalysisreductive cleavage |
| spellingShingle | Vipin Kumar Jain Diastereoselective Synthesis of (–)-Bestatin, Epibestatin, Phebestin and (3S,4R)-4-Amino-3-hydroxy-5-phenylpentanoic Acid from an Aldehyde Derived from d-Phenylalanine SynOpen asymmetric hydroxylation organocatalysis reductive cleavage |
| title | Diastereoselective Synthesis of (–)-Bestatin, Epibestatin, Phebestin and (3S,4R)-4-Amino-3-hydroxy-5-phenylpentanoic Acid from an Aldehyde Derived from d-Phenylalanine |
| title_full | Diastereoselective Synthesis of (–)-Bestatin, Epibestatin, Phebestin and (3S,4R)-4-Amino-3-hydroxy-5-phenylpentanoic Acid from an Aldehyde Derived from d-Phenylalanine |
| title_fullStr | Diastereoselective Synthesis of (–)-Bestatin, Epibestatin, Phebestin and (3S,4R)-4-Amino-3-hydroxy-5-phenylpentanoic Acid from an Aldehyde Derived from d-Phenylalanine |
| title_full_unstemmed | Diastereoselective Synthesis of (–)-Bestatin, Epibestatin, Phebestin and (3S,4R)-4-Amino-3-hydroxy-5-phenylpentanoic Acid from an Aldehyde Derived from d-Phenylalanine |
| title_short | Diastereoselective Synthesis of (–)-Bestatin, Epibestatin, Phebestin and (3S,4R)-4-Amino-3-hydroxy-5-phenylpentanoic Acid from an Aldehyde Derived from d-Phenylalanine |
| title_sort | diastereoselective synthesis of bestatin epibestatin phebestin and 3s 4r 4 amino 3 hydroxy 5 phenylpentanoic acid from an aldehyde derived from d phenylalanine |
| topic | asymmetric hydroxylation organocatalysis reductive cleavage |
| url | http://www.thieme-connect.de/DOI/DOI?10.1055/s-0039-1690223 |
| work_keys_str_mv | AT vipinkumarjain diastereoselectivesynthesisofbestatinepibestatinphebestinand3s4r4amino3hydroxy5phenylpentanoicacidfromanaldehydederivedfromdphenylalanine |