Short-Step Anodic Synthesis of Color-Tunable Emissive Nucleoside Analogues

Abstract

Since natural nucleobases are not emissive, emissive nucleoside analogues have been widely used to monitor fundamental biochemical transformations directly. Nowadays, useful libraries of synthetic emissive nucleoside analogues have been constructed and researchers have a wide variety of choices. A typical approach to prepare these synthetic probes is “pre-formed” manner, namely, a glycosylation is carried out using emissive nucleobases under carefully selected conditions to control both stereoselectivity at the anomeric position and regioselectivity of the aglycon attack. Such a glycosylation usually requires a time-consuming trial-and-error procedure, because the reaction selectivities are affected by the interaction of the protected groups of both the sugar and aglycon. On the other hand, the preparation approach based on “post-forming” manner would be effective since a cumbersome glycosylation could be done in an early synthesis stage. We have been developing anodic intermolecular cycloadditions in lithium perchlorate/nitromethane electrolyte solution. In this electrolyte solution, unactivated alkenes can function as effective carbon nucleophiles to trap anodically generated cations or radical cations, leading to the formation of corresponding ring systems. Especially, we previously reported that the anodic oxidation of methoxyphenols in the presence of alkene nucleophiles was able to give highly emissive dihydrobenzofuran derivatives through formal [3 + 2] cycloadditions. These results in hand, we herein demonstrate a short-step “post-forming” synthesis of novel emissive nucleoside analogues based on the anodic cycloadditions. Initially, we tried to attach a methallyl moiety to a ribose scaffold as an alkene nucleophile. After the numerous optimizations, we finally accomplished the stereoselective allylation at the anomeric position to obtain both a- and b-methallyl ribose and we were able to use each corresponding pure form for further transformations. The anomeric stereochemistry was successfully fixed at the first synthesis stage. Methoxyphenols were then anodically oxidized in the presence of the methallyl ribose and we found that emissive dihydrobenzofuran structures were able to be constructed on the sugar moiety in one step. The emission color was significantly affected by the carbonyl substituent, ranging roughly from 400 nm to 500 nm with long stokes shift values. In the presentation, the synthesis details and photophysical properties will be discussed.