Enantioselective Synthesis of (2S ,3S )-epi -Oxetin and Its Incorporation into Conformationally Constrained Pyrrolidinyl PNA with an Oxetane Backbone
| Autor: | Roderick W. Bates, Pattarakiat Seankongsuk, Viwat Vchirawongkwin, Tirayut Vilaivan, Panuwat Padungros |
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| Rok vydání: | 2017 |
| Předmět: |
chemistry.chemical_classification
010405 organic chemistry Stereochemistry Organic Chemistry Enantioselective synthesis Epoxide 010402 general chemistry Oxetane Ring (chemistry) 01 natural sciences 0104 chemical sciences Amino acid chemistry.chemical_compound chemistry biological sciences Peptide synthesis Azide DNA |
| Zdroj: | Asian Journal of Organic Chemistry. 6:551-560 |
| ISSN: | 2193-5807 |
| DOI: | 10.1002/ajoc.201600575 |
| Popis: | Fmoc-protected (2S,3S)-epi-oxetin was synthesized from (E)-4-(benzyloxy)but-2-enal via enantioselective organocatalytic epoxidation, epoxide ring opening with azide, alcohol activation and ring closure, followed by functional groups manipulation in 8 steps with 12% overall yield and 94%ee. The amino acid was used as a building block for a new conformationally constrained pyrrolidinyl PNA with an oxetane-containing backbone. The unexpected sensitivity of the oxetane backbone under standard Fmoc-solid phase peptide synthesis conditions posed considerable synthetic challenges, and the mechanism for acid-catalyzed degradation was proposed. In addition, the DNA and RNA binding properties of the oxetane PNA were investigated. The presence of the oxetane ring decreased the stability of the PNA*DNA and PNA*RNA duplexes when compared to the PNA with cyclobutane-containing backbone, which could be explained by the flattening of the oxetane ring, leading to a suboptimal torsional angle. |
| Databáze: | OpenAIRE |
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