Synthesis of Chiral Carbocyclic Ribonucleotides

Abstract

The carbocyclic analogs of CMP, UMP, GMP, IMP, and ribo-TMP, of the same absolute configuration as the naturally occurring beta-D-ribofuranose-based ribonucleoside monophosphates, have been synthesized. The synthetic route employed Mitsunobu coupling of the heterocycles, appropriately protected where necessary, with a differentially protected, chiral carbocyclic core.

Synthesis of phosphoramidites of isoGNA, an isomer of glycerol nucleic acid

“…In the cytosine series we found that the normal N 4 -benzoyl or N 4 -acetyl protected cytosine did not give satisfactory yields under the Mitsunobu conditions. The best yields were achieved with N 4 -isobutyrylcytosine as the nucleophile [19–21]. In the guanine series, the N 2 -isobutyryl, O 6 -diphenylcarbamoyl protected guanine worked well (Scheme 3) [22].…”