Chemical models of secondary RNA structures such as hairpins, bulges and three-way junctions might be obtained by ring-closing metathesis (RCM) technology. Thus, several nucleoside monomers containing terminal alkenes have been synthesised and used in the construction of dinucleotides, on which RCM reactions have been performed. Hereby, the dinucleotides are constrained by large additional unsaturated ring structures. We have also successfully applied a tandem RCM-hydrogenation approach giving saturated rings. These dinucleotides will, when incorporated into oligonucleotides, introduce structural “bends” as found in secondary and tertiary structures.
Posters
Conformationally Restricted Dinucleotides Tandem Ring Closing Metathesis and Hydrogenation Approach [PDF] (Philip Børsting)
Publications
Sharma, Pawan K; Mikkelsen, Birgitte H; Christensen, Mikkel S; Nielsen, Katrine E; Kirchhoff, Claus; Pedersen, Søren L; Sørensen, Anders M; Østergaard, Kirsten; Petersen, Michael and Nielsen, Poul. A cyclic dinucleotide with a four-carbon 5_-C-to-5_-C connection; synthesis by RCM, NMR-examination and incorporation into secondary nucleic acid structures. Org. Biomol. Chem., 2006, 4, 2433–2445. [Abstract]
Børsting, Philip; Christensen, Mikkel S.; Steffansen, Signe I.; Nielsen, Poul. Synthesis of dinucleotides with 2'-C to phosphate connections by ring-closing metathesis. Tetrahedron, 2006, 62, 1139-1149. [Abstract]
Borsting, Philip; Nielsen, Katrine E.; Nielsen, Poul. Stabilisation of a nucleic acid three-way junction by an oligonucleotide containing a single 2'-C to 3'-O-phosphate butylene linkage prepared by a tandem RCM-hydrogenation method. Organic & Biomolecular Chemistry, 2005, 3, 2183-2190. [Abstract]
Børsting, Philip; Freitag, Morten and Nielsen, Poul. Dinucleotides containing two allyl groups by combinations of allyl phosphotriesters, 5-allyl-, 2'-O-allyl- and 2'-arabino-O-allyl uridine derivatives as substrates for ring-closing metathesis. Tetrahedron, 2004, 10955-10966 [Abstract]
Kirchhoff, Claus; Nielsen, Poul. Dinucleotides of 4'-C-vinyl- and 5'-C-allylthymidine as substrates for ring-closing metathesis reactions. Tetrahedron Letters, 2003, 44, 6475-6478. [Abstract]
Børsting, Philip; Nielsen, Poul: Tandem ring-closing metathesis and hydrogenation towards cyclic dinucleotides. Chem. Commun, 2002, 2140-2141. [Abstract]
Børsting, Philip; Sørensen, Anders M.; Nielsen, Poul: A Ring-Closing Metathesis Strategy Towards Conformationally Restricted Di-and Trinucleotides, Synthesis, 2002, 6; 797-801. [Synthesis]
Sørensen, Anders M.; Nielsen, Katrine E.; Vogg, Barbara; Jacobsen, Jens Peter and Nielsen, Poul: Synthesis and NMR-studies of dinucleotides with conformationally restricted cyclic phosphotriester linkages, Tetrahedron, 2001, 57(51); 10191-10201.[Abstract]