Synthesis of deuterated ribo nucleosides, N-protected phosphoramidites, and oligonucleotides

摘要

The present invention is directed towards the synthesis of high purity deuterated sugars, deuterated phosphoramidites, deuterated nucleobases, deuterated nucleosides, deuterated oligonucleotides, and deuterated RNA's of defined sequences which can exhibit biochemically useful and biologically valuable properties, thus having potential for therapeutic uses.

主权项

1. A method for preparing a modified ribo-oligonucleotide that contains deuterium comprising the steps of:
providing a ribose structure; converting said ribose structure to an α/β ribofuranoside; incorporating deuterium at one or more positions of said α/β ribofuranoside to form a deuterated α/β ribofuranoside having at least one deuterium at a 2 prime position, one deuterium at a 3 prime position, and 2 deuterium at a 5 prime position; incorporating a plurality of benzoyl groups at one or more positions of said deuterated α/β ribofuranoside structure; incorporating an acetate ion at one position of said deuterated α/β ribofuranoside structure; incorporating a nitrogenous base structure to said deuterated α/β ribofuranoside structure, thereby forming a first deuterated nucleoside; providing at least a second a ribose structure; converting said second ribose structure to a second α/β ribofuranoside; incorporating deuterium at one or more positions of said second α/β ribofuranoside to form a second deuterated α/β ribofuranoside having at least one deuterium at a 2 prime position, one deuterium at a 3 prime position, and 2 deuterium at a 5 prime position; incorporating a plurality of benzoyl groups at one or more positions of said second deuterated α/β ribofuranoside structure; incorporating an acetate ion at one position of said second deuterated α/β ribofuranoside structure; incorporating a nitrogenous base structure to said second deuterated α/β ribofuranoside structure, thereby forming a second deuterated nucleoside; and chemically linking said first deuterated nucleoside with said second deuterated nucleoside.