Synthesis of diastereomeric mixtures of 5'-C-hydroxymethylthymidine and introduction of a novel class of C-hydroxymethyl functionalised oligodeoxynucleotides.
Novel 5'-C-hydroxymethyl substituted derivatives of thymidine have been prepared by dihydroxylation of the 5'C-methylene nucleoside 1. Osmium tetraoxide catalysed dihydroxylation of 1 afforded a 3:2 epimeric mixture of diols 2, whereas asymmetric dihydroxylation using AD-mix-alpha and AD-mix-beta resulted in mixtures 3 and 4 of the two epimeric diols, both enriched with the same diastereomer. Nucleosides 2 were transformed into phosphoramidites 8 which were used for solid phase synthesis of oligodeoxynucleotides (ODNs) containing 5'-C-(hydroxymethyl) functionalised thymidine monomers. This novel class of C-hydroxymethyl modified ODN-analogues exhibited promising affinity towards both complementary DNA and RNA as well as resistance towards 3'-exonucleolytic degradation.
Fensholdt
J
J
Department of Chemistry, Odense University, Denmark.
Wengel
J
J
D001483:Base Sequence; D006900:Hydroxylation; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis*; D009993:Osmium Tetroxide; D013237:Stereoisomerism; D013936:Thymidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis
C103326:5'-C-hydroxymethylthymidine; D009838:Oligodeoxyribonucleotides; D009993:Osmium Tetroxide; D013936:Thymidine