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Enantioselective Synthesis of (2 S ,3 S )‐ epi ‐Oxetin and Its Incorporation into Conformationally Constrained Pyrrolidinyl PNA with an Oxetane Backbone
Author(s) -
Seankongsuk Pattarakiat,
Vchirawongkwin Viwat,
Bates Roderick W.,
Padungros Panuwat,
Vilaivan Tirayut
Publication year - 2017
Publication title -
asian journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.846
H-Index - 44
eISSN - 2193-5815
pISSN - 2193-5807
DOI - 10.1002/ajoc.201600575
Subject(s) - oxetane , chemistry , enantioselective synthesis , epoxide , stereochemistry , ring (chemistry) , peptidomimetic , cyclobutane , combinatorial chemistry , peptide , catalysis , organic chemistry , biochemistry
Fmoc‐protected (2 S ,3 S )‐ 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‐group manipulation in eight 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 posed considerable synthetic challenges under standard Fmoc‐solid‐phase peptide synthesis conditions, and a mechanism for acid‐catalyzed degradation was proposed. In addition, the DNA‐ and RNA‐binding properties of the oxetane PNA were investigated. The presence of an oxetane ring decreased the stability of the PNA ⋅ DNA and PNA ⋅ RNA duplexes when compared to PNA with a cyclobutane‐containing backbone, which could be explained by the flattening of the oxetane ring, leading to a suboptimal torsional angle.