Regioselective Mitsunobu Reaction of Partially Protected Uridine

Abstract

Mitsunobu reaction of partially acylated uridine proceeds with high regioselectivity for intramolecular SN2 anhydro linkage closuring. Under the reaction conditions, an isomeric mixture of diacyl uridine derivatives with either free 2'- or 3'-hydroxyl group was transformed into a single cyclonucleosidic product, 2,2'-anhydro-3',5'-di-O-acyluridine. This paper presents a possible mechanism of the reactions, the explanation of observed phenomenon based on semiempirical and density functional theory (DFT) calculations and possible utility of this synthetic pathway.

Synthesis of 2′-O-Methyl/2′-O-MOE-L-Nucleoside Derivatives and Their Applications: Preparation of G-Quadruplexes, Their Characterization, and Stability Studies

“…Subsequent treatment of 10 with methyl propiolate in an EtOH–H 2 O mixture at reflux for 4 h furnished anhydro- l -uridine 11 in 65% isolated yield. To synthesize the 2′- O -Me derivative, we used the procedure described by Szlenkier et al 17 for d -nucleosides due to the availability of reagents and the good yield of the reaction. Hence, compound 11 was added to a suspension of magnesium and iodine in methanol, and the mixture was stirred under reflux for 5 h. However, instead of the desired compound 12 , a derivative, resulting from the iodination of 11 at the nucleobase 5-position, was isolated (40%).…”

“…Subsequent treatment with aqueous ammonia (32%) in 1,4-dioxane afforded 16. Finally, deprotection of the TBS groups with tetrabutylammonium fluoride (TBAF) in THF led to 2′-O-methyl-L-cytidine (17) in 58% overall yield and 4 steps from 12.…”