New chemo-enzymatic route for the synthesis of chiral glycidyl esters ((S)-ethyl and (S)-methyl-4,5-epoxypentanoates) from renewable resources

Abstract

<p>Chiral glycidyl esters – such as (S)-ethyl- or (S)-methyl-4,5-epoxypentanoates - are valuable precursors in many chemical syntheses. Until recently, these compounds were synthesized from glutamic acid in four steps (deamination, reduction, tosylation and epoxide formation) in low to average global yield (20-50%). Moreover, this procedure requires some harmful reagents such as sodium nitrite (toxic and ecotoxic) and boron hydride (carcinogen).</p> <p>Herein, to access these chiral glycidyl esters, we propose a safer chemo-enzymatic synthetic pathway starting from levoglucosenone (aka LGO, CAS 37112-31-5), a biobased compound obtained through the flash pyrolysis of cellulose. Firstly, LGO was submitted to a lipase-mediated Baeyer-Villiger oxidation followed by an acidic hydrolysis to afford (S)-γ-hydroxymethyl-α,β-butenolide. The latter then underwent a palladium-catalyzed hydrogenation to give (S)-γ-hydroxymethyl-γ-butyrolactone. Finally, after tosylation, the corresponding intermediate was treated with sodium ethoxide/methoxide to afford (S)-Ethyl and (S)-Methyl-4,5-epoxypentanoates in 57% yield, respectively. </p>