Synthesis of a novel conformationally locked carbocyclic nucleoside ring system.
[reaction: see text] A fast and efficient synthetic route to novel Northern locked carbocyclic nucleosides (as precursors of carbocyclic locked nucleic acids or cLNAs) is described. The target nucleoside with a oxabicyclo[2.2.1]heptane ring system was prepared from a simple starting material, diethyl malonate. Ring closure by intramolecular O-alkylation provided the target ring system as the major isomer over the [3.2.0] oxetane system. The adenine moiety was introduced through a reactive triflate after inversion of the stereochemistry of the corresponding alcohol by oxidation and reduction.
Kim
Hak Sung
HS
Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Jacobson
Kenneth A
KA
D000225:Adenine / Q000737:chemistry; D000478:Alkylation; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009705:Nucleosides / Q000138:chemical synthesis*; D010084:Oxidation-Reduction; D013237:Stereoisomerism
D007202:Indicators and Reagents; D009705:Nucleosides; D000225:Adenine