Synthesis of Substituted Benzyl Homo‐C‐Ribonucleosides and ‐Nucleotides as Carba Analogues of Phosphoribosylanthranilate

Abstract

AbstractNew 2‐substituted benzyl C‐ribonucleosides and ‐nucleotides were designed as carba analogues of phosphoribosylanthranilate, a key intermediate in tryptophan biosynthesis. The synthesis was based on the preparation of TBS‐protected 2‐bromobenzyl C‐ribonucleoside 4a by addition of (2‐bromobenzyl)magnesium bromide to ribonolactone followed by reduction and subsequent functional group transformations. Pd‐catalyzed hydrogenation, cross‐couplings, amination or hydroxylation, as well as lithiation followed by reaction with CO2 and amidations, gave a large series of 2‐alkyl‐, 2‐(het)aryl, 2‐amino, 2‐hydroxy, 2‐carboxy and 2‐carbamoyl derivatives that were deprotected to afford free homo‐C‐ribonucleosides. Some of the title nucleosides were converted to 5′‐O‐phosphates.