Synthesis and NMR-studies of dinucleotides with conformationally restricted cyclic phosphotriester linkages

Four diastereomeric dinucleotides in which the phosphodiester linkages are conformationally restricted in cyclic phosphotriester structures are synthesised. From the epimeric 5'-C-vinyl thymidine derivatives, dinucleotides containing two terminal alkene moieties are constructed via standard pho...

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Bibliographic Details
Published inTetrahedron Vol. 57; no. 51; pp. 10191 - 10201
Main Authors Sorensen, AM, Nielsen, KE, Vogg, B, Jacobsen, JP, Nielsen, P
Format Journal Article
LanguageEnglish
Published OXFORD Elsevier 17.12.2001
Subjects
Chemistry
Chemistry, Organic
Physical Sciences
Science & Technology
configuration
STABILITY
conformation
OLEFIN METATHESIS
ring-closing metathesis
OLIGONUCLEOTIDES
PEPTIDES
DNA
LOCKED NUCLEIC-ACIDS
CHEMICAL-SYNTHESIS
BICYCLIC NUCLEOSIDES
DUPLEX
nucleotides
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Summary:Four diastereomeric dinucleotides in which the phosphodiester linkages are conformationally restricted in cyclic phosphotriester structures are synthesised. From the epimeric 5'-C-vinyl thymidine derivatives, dinucleotides containing two terminal alkene moieties are constructed via standard phosphoramidite chemistry, and applied as substrates in ring-closing metathesis (RCM) reactions. Hereby, four diastereomeric dinucleotides with seven membered phosphepine rings in the inter-nucleoside linkages are obtained and separated, and their configurations elucidated by advanced NMR-studies in combination with restrained molecular dynamics (rMD) simulations. The seven membered rings are found to give some degree of conformational restriction in the natural nucleic acid backbone, and one of the four dinucleotides is found to favour stacking between the two adjacent thymine moieties. (C) 2001 Elsevier Science Ltd. All rights reserved.
ISSN:0040-4020
1464-5416
DOI:10.1016/S0040-4020(01)01047-X