Stereochemical Studies of Odorous 2-Substituted-3(2H)-furanones by Vibrational Circular Dichroism

Abstract

Chiral naturally occurring aroma compounds often exhibit enantiomeric excesses due to their stereoselective biogenesis. In general, significant organoleptic differences are perceived between these enantiomers. Chiral 2-substituted-3(2H)-furanones, featuring a unique keto-enol tautomer, the cause of their racemization, have been known to play an important role in flavor because of their extremely low threshold values and their burnt sugar odor characteristics. Since the discovery of these important aroma chemicals, they have been used in large quantities as raw materials in the flavor and fragrance industry. However, absolute configurations of these furanone derivatives have remained ambiguous for the past 40 years. Here optical resolutions of 2,5-dimethyl-4-hydroxy-3(2H)-furanone, 2,5-dimethyl-4-methoxy-3(2H)-furanone, and 4-acetoxy-2,5-dimethyl-3(2H)-furanone were accomplished using chiral CO(2) supercritical fluid chromatography (SFC). Their absolute configurations were unraveled for the first time using the vibrational circular dichroism (VCD) technique as well as by chemical relay reactions. Odor evaluation of each enantiomer revealed relationships between their configurations and odor activities.

An enzymatic approach to the synthesis of optically pure (3R)- and (3S)-enantiomers of green tea flavor compound 3-hydroxy-3-methylnonane-2,4-dione

“…We have recently 1 The assay of AAS activity in the absence of catalytic ThDP and MgSO4 revealed a decrease of the reaction rate of ca.40%.…”

“…Many of the substances able to stimulate taste or olfactory receptors have chiral structures and most of them are present in nature as enantiomeric mixtures with considerable predominance of one of the two enantiomers (scalemic mixtures) [1][2][3]. It is well known, however, that often only one of the enantiomers is responsible for the perception of taste or odor.…”

“…The resulting mixture was gently shaken at 30 • C for 24 h and then warmed (80 • C, 20 min), centrifuged (11,800 × g, 20 min), and the supernatant was extracted with AcOEt (3× 15 mL). The organic phase was dried (Na 2 SO 4 ), concentrated, and eluted from a short column of silica gel (1 × 4 cm) with cyclohexane-AcOEt 2:1 (flow rate 5 cm/min) to give the anti diol (2S,3S)-4 (3 mg, 10%) slightly contaminated by uncharacterized by-products;1 H NMR (selected data): ı 3.80-3.90 (m, 1H); 3.95 (s, 1H), 2.60 (ddd, J = 7.0 Hz, J = 9.0 Hz, J = 15.0 Hz, 1H), 2,45 (ddd, J = 7.0 Hz, J = 9.0 Hz, J = 15.0 Hz, 1H), 1.42 (s, 3H), 1.05 (d, J = 7.0 Hz, 3H), 0.88 (t, J = 7.0 Hz, 3H). GC-MS: retention time (min) 31.6; MS (70 eV, EI): m/z (%) 189 (≤1%) [M+H] + , 144 (15%), 89 (100%) [MH−C 5 H 11 CO] + , 71 (50%) [C 5 H 11 ] + .…”

Historical Review on the Identification of Mesifurane, 2,5-Dimethyl-4-methoxy-3(2H)-furanone, and Its Occurrence in Berries and Fruits

“…66 Emura et al resolved the structures of the enantiomers of both furaneol and mesifurane by enantioselective carbon dioxide supercritical-fluid chromatography, and the structures were defined by chemical relay reactions and a vibrational-circular-dichroism technique. 72 The ( R )-(+) isomer of mesifurane had intensive flavor characteristics of burnt caramel, 72 representing the later-eluting enantiomer in the chiral GC analyses of Bruche et al 70 and Fisher and Hammerschmidt. 71 Isotope-ratio mass spectrometry after chiral GC (GC-IRMS) may be used to reveal the origins of the compounds (e.g., for authentication of the sample).…”

Progress in the Chemistry of Organic Natural Products 100

“…Interestingly, this pair of closely structurally related furanones has opposite optical rotations even though both are (R). However, the analogous odiferous compounds (+)-(R)-270(305,306) and (+)-(R)-271(307), with equal structural changes to the 268 and 269 pair, display the same optical rotation and configuration. The absolute configuration assignments of 270 and 271 were also determined by VCD.…”