First organocatalytic, diastereoselective synthesis of tRNA wobble nucleosides: (R)- and (S)-methoxycarbonylhydroxymethyluridines (mchm5Us) and their acid analogues (chm5Us)

TL;DR

Scientists developed a new method to selectively synthesize two forms of modified RNA building blocks important for genetic code flexibility.

Contribution

First organocatalytic, diastereoselective synthesis of tRNA wobble nucleosides mchm5Us and chm5Us.

Findings

A diastereoselective synthesis of (R)- and (S)-mchm5Us was achieved using cyanosilylation and Pinner reaction.

The method was extended to synthesize their acid analogues, (R)- and (S)-chm5Us.

The approach uses organo- and organometallic catalysis for efficient and selective production.

Abstract

A diastereoselective organocatalytic synthesis of (R)- and (S)-methoxycarbonylhydroxymethyluridines (mchm5Us) and their acid analogues (chm5Us) was developed. The method employs organo- and organometallic-catalyzed cyanosilylation of 5-formyluridine to yield diastereomerically enriched TMS-protected cyanohydrins, which are converted via a Pinner reaction to (R)- and (S)-mchm5Us, then hydrolyzed to (R)- and (S)-chm5Us.

First diastereoselective synthesis of biologically relevant (R)- and (S)- methoxycarbonylhydroxymethyluridines (mchm5Us) and their acid analogues (chm5Us) was developed.

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