A green and sustainable approach: celebrating the 30th anniversary of the asymmetric l-menthol process.

Takasago has been devoted to producing l-menthol since 1954, and our long history of manufacturing this important aroma chemical is reviewed here. The current asymmetric catalytic process had its 30th anniversary in 2013. Our l-menthol process is considered carbon-neutral, and, therefore, 'green' and sustainable. It uses renewable myrcene obtained from gum rosin as a starting material. In addition, the Rh-BINAP (=2,2'-bis(diphenylphosphino)-1,1'-binaphthyl) catalytic system is highly efficient. This pathway not only leads l-menthol, but a variety of 100% biobased aroma chemical products as well. By measuring the (14) C levels in a material, one can determine the percentage of carbon that is biobased. This biobased assay, described as the ratio plant-derived C/fossil-derived C, can clarify how renewable a product really is. This will be highlighted for several of Takasago's key aroma chemicals.

A vibrational circular dichroism approach to the determination of the absolute configurations of flavorous 5-substituted-2(5H)-furanones.

Sotolon (1) and maple furanone (2) are naturally occurring chiral furanones. These 5-substituted-2(5H)-furanones are industrially significant aroma compounds due to their characteristic organoleptic properties and extraordinarily low odor thresholds. Each enantiomer of 1 and 2 was successfully obtained by preparative enantioselective supercritical fluid chromatography. The absolute configuration of 1 was confirmed as (R)-(-)-1 and (S)-(+)-1 by adopting the vibrational circular dichroism (VCD) approach. The absolute configuration of 2, which has remained ambiguous since its discovery in 1957, was determined as (R)-(+)-2 and (S)-(-)-2 for the first time by the VCD technique. Surprisingly, the signs of the optical rotation of 2 are opposite of those of 1 regardless of their identical absolute configurations. This observation emphasizes the risk in absolute configurational assignments based on comparison of optical rotation signs of similar structures. Odor evaluation of the enantiomers of 2 revealed different odor intensities.

Stereochemical study of a novel tautomeric furanone, homofuraneol.

A mixture of tautomers with unique keto-enol structures, 5-ethyl-4-hydroxy-2-methylfuran-3(2H)-one and 2-ethyl-4-hydroxy-5-methylfuran-3(2H)-one (EHMF, homofuraneol, 1a and 1b), comprises four structural isomers including their enantiomers. The four isomers were successfully separated by chromatographic optical resolution, and their odor evaluation was performed. Determination of the absolute chemistry of 1a and 1b were accomplished for the first time by direct measurement of the VCD spectra of their methyl ether derivatives 4a and 4b compared with the calculated ones as well as chemical relay reaction. The relationship between odor characteristics and stereochemistry was also examined.

Supersensitive detection and discrimination of enantiomers by dorsal olfactory receptors: evidence for hierarchical odour coding.

Enantiomeric pairs of mirror-image molecular structures are difficult to resolve by instrumental analyses. The human olfactory system, however, discriminates (-)-wine lactone from its (+)-form rapidly within seconds. To gain insight into receptor coding of enantiomers, we compared behavioural detection and discrimination thresholds of wild-type mice with those of ΔD mice in which all dorsal olfactory receptors are genetically ablated. Surprisingly, wild-type mice displayed an exquisite "supersensitivity" to enantiomeric pairs of wine lactones and carvones. They were capable of supersensitive discrimination of enantiomers, consistent with their high detection sensitivity. In contrast, ΔD mice showed selective major loss of sensitivity to the (+)-enantiomers. The resulting 10(8)-fold differential sensitivity of ΔD mice to (-)- vs. (+)-wine lactone matched that observed in humans. This suggests that humans lack highly sensitive orthologous dorsal receptors for the (+)-enantiomer, similarly to ΔD mice. Moreover, ΔD mice showed >10(10)-fold reductions in enantiomer discrimination sensitivity compared to wild-type mice. ΔD mice detected one or both of the (-)- and (+)-enantiomers over a wide concentration range, but were unable to discriminate them. This "enantiomer odour discrimination paradox" indicates that the most sensitive dorsal receptors play a critical role in hierarchical odour coding for enantiomer identification.

Stereochemical studies of odorous 2-substituted-3(2H)-furanones by vibrational circular dichroism.

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.

Stereochemical study of chiral tautomeric flavorous furanones by vibrational circular dichroism.

2-Substituted-3(2H)-furanone derivatives are industrially significant aroma compounds possessing a unique keto-enol tautomeric feature causing their racemization. Absolute configurations of two flavorous furanones, which have remained unclear for the past 40 years since their discovery, were clarified by the vibrational circular dichroism technique as well as chemical relay reactions. Odor evaluation of each enantiomer revealed relationships between their configurations and their odor activities.