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

Abstract

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.

Sustainable Synthesis and Polycondensation of Levoglucosenone‐Cyrene‐Based Bicyclic Diol Monomer: Access to Renewable Polyesters

“…To the best of our knowledge, no further optimizations or chemical transformations were performed to take advantage of this promising molecule that offers a playground for chemists because of its two ketone moieties. By building on our experience with LGO upgrading through sustainable synthetic processes, we investigated the implementation of the aforementioned Baeyer–Villiger‐based strategy to LGO‐Cyrene TM to access the corresponding 2H‐HBO‐HBO as a new bio‐based AA′‐type diol monomer with the aim to produce renewable polyesters with the HBO motif (Scheme ).…”

Chemo-Enzymatic Synthesis and Free Radical Polymerization of Renewable Acrylate Monomers from Cellulose-Based Lactones

“…The first route involved a lipase-mediated Baeyer–Villiger oxidation of LGO whereas the more recent route is a solvent-free and catalyst-free H 2 O 2 -mediated Baeyer–Villiger oxidation . The versatility of HBO has been employed to access not only valuable chiral building blocks such as chiral epoxides but also end products such as enantiopure ( S )-dairy lactone employed as a butter-like flavoring agent in food sectors such as the snack, ice cream, and bakery industries.…”

“…NMR (CDCl3, 300 MHz): δH 1.50 (m, 4H, H8,9), 1.70 (m, 2H, H10), 2.89 (m, 2H, H3),3.69 (m, 4H, H5,7), 4.60 (t, 0.51H, J = 1.9 Hz, H6) and its diastereomeric peak at 4.65 (t, 0.56H, J = 1.9 Hz, H6), 4.70 (m, 1H, H4), 5.62 (m, 1H, H11c), 6.20 (m, 1H, H11d) 13. C NMR (CDCl3, 75 MHz): δC 18.9, 19.2 (C9), 25.3 (C8), 29.7 (C3), 30.3 (C10), 61.8, 62.3 (C7), 68.5, 68.6 (C5), 75.5, 75.7 (C4), 98.6, 99.2 (C6), 121.5, 121.7 (C2), 134.3, 134.5 (C11), 170.1, 170.3 (C1).…”

Making natural products from renewable feedstocks: back to the roots?

“…A concise synthesis of the avoring compound dairy lactone (149), named aer its natural occurrence in cow milk as well as its dairy-like odor and avor, 268,269 was presented in 2016 using the levoglucosenonederived g-lactone 2H-HBO (118). 270 To create an electrophilic species from alcohol 118, it was converted to epoxide 146 via the respective tosylate and alkaline transesterication (Scheme 24). Reaction with lithiated 1-heptyne (147) and acidic trans-esterication furnished lactone 148, which was hydrogenated to (+)-149 using a Lindlar catalyst.…”