STUDIES ON TRIESTER SYNTHESIS OF OLIGODEOXYRIBONUCLEOTIDES
Abstract
5'-o-Dimethoxytrityldeoxyribonucleoside-3' p-chlorophenyl phosphodiesters were prepared as key intermediates in oligonucleotide synthesis. These compounds can be easily prepared in high yield and in pure form by precipitation as barium salts. Subsequent investigations have demonstrated that the barium salts of the protected 5'-o-dimethoxytrityldeoxyribonucleoside-3' p-chlorophenyl phosphates can be employed directly in phosphotriester condensation reactions. A new class of condensing reagents, the arylsulfonyl 4-nitroimidazoles, have been shown to promote efficient joining of oligonucleotide blocks in high yield. This reagent has been used to construct a number of oligonucleotides. The chemically synthesized oligonucleotides have proved to be functional hybridization probes for detecting and sequencing specific messages from total messenger RNA. ('31)P NMR work has demonstrated a unique method by which to study the mechanism of triester synthesis structurally and quantitatively. The kinetic and structural data together provide a unified mechanism for triester synthesis. Furthermore, these data have evaluated the effectiveness of several condensing reagents, and have implicated new methods for synthesizing oligonucleotides.
Degree
Ph.D.
Subject Area
Organic chemistry
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