Approaches to the chemical synthesis of oligoribonucleotides

by Aria Libi. Schifman

Institution: McGill University
Department: Department of Chemistry
Degree: PhD
Year: 1979
Keywords: Nucleic acids.
Record ID: 1545436
Full text PDF: http://digitool.library.mcgill.ca/thesisfile68515.pdf


The conversion of 8,2'-S-anhydroadenosine to adenosine was studied in order to determine the feasibility of using 8,2'-S-anhydropurine nucleosides for oligoribonucleotide synthesis. Sulfoxide derivatives of 8,2'-S-anhydroadenosine were prepared efficiently; however when they were subjected to Pummerer reaction conditions in an attempt to introduce a 2'-substituent, extensive decomposition occurred. The synthesis of t-butyldimethylsilyl derivatives of cytidine and guanosine nucleosides was accomplished. Preparations were fast and simple, and most of the desired 2',5' diprotected nucleosides were obtained in greater than 50% yield from the nonsilylated nucleosides. Using the phosphorodichlorodite procedure, silylated nucleosides were easily incorporated into ribonucleotides. In addition to 3',5'-linked ribonucleotides, 2',5'- and symmetrically linked ribonucleotides were also prepared. ('1)H, ('13)C and ('31)P nuclear magnetic resonance spectroscopy was utilized in elucidating the structure of ribonucleotides; enzyme degradations on the completely deprotected ribonucleotides confirmed the position of the phosphate linkages.