Chemo-Enzymatic Synthesis of Chiral Epoxides Ethyl and Methyl (S)-3-(Oxiran-2-yl)propanoates from Renewable Levoglucosenone: An Access to Enantiopure (S)-Dairy Lactone

Aurélien Peru (1) , Amandine Flourat (1) , Christian Gunawan , Warwick Raverty , Martyn Jevric , Ben Greatrex , Florent Allais (2, 3)

1 IJPB - Institut Jean-Pierre Bourgin
2 GMPA - Génie et Microbiologie des Procédés Alimentaires
3 ABI - Agro-Biotechnologies Industrielles

Chiral epoxides—such as ethyl and methyl (S)-3-(oxiran-2-yl)propanoates ((S)-1a/1b)—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 moderate overall yield (20%–50%). Moreover, this procedure requires some harmful reagents such as sodium nitrite ((eco)toxic) and borane (carcinogen). Herein, starting from levoglucosenone (LGO), a biobased chiral compound obtained through the flash pyrolysis of acidified cellulose, we propose a safer and more sustainable chemo-enzymatic synthetic pathway involving lipase-mediated Baeyer-Villiger oxidation, palladium-catalyzed hydrogenation, tosylation and treatment with sodium ethoxide/methoxide as key steps. This route afforded ethyl and methyl (S)-3-(oxiran-2-yl)propanoates in 57% overall yield, respectively. To demonstrate the potentiality of this new synthetic pathway from LGO, the synthesis of high value-added (S)-dairy lactone was undertaken from these epoxides and provided the target in 37% overall yield from LGO.

Keywords: levoglucosenone; chirality; total synthesis

Keywords: epoxide; flavor

Domains: Life Sciences [q-bio]

Aurélien Peru, Amandine Flourat, Christian Gunawan, Warwick Raverty, Martyn Jevric, et al.. Chemo-Enzymatic Synthesis of Chiral Epoxides Ethyl and Methyl (S)-3-(Oxiran-2-yl)propanoates from Renewable Levoglucosenone: An Access to Enantiopure (S)-Dairy Lactone. Molecules, 2016, 21 (8), pp.988. ⟨10.3390/molecules21080988⟩. ⟨hal-01598617⟩