Cubebol

Abstract: The use of (−)-cubebol, or (−)-(1R,4S,5R,6R,7S,10R)-7-isopropyl-4, 10-dimethyl-tricyclo[4400(1,5)]decan-4-ol of the formula as a flavoring, and the foods and various other products flavored with cubebol

Abstract: Terpenes are an important and extremely versatile class of secondary metabolites that are commercially used in the pharmaceutical, food and cosmetics sectors. Genome mining of different fungal collections has revealed the genetic basis for a steadily increasing number of putative terpene synthases without any detailed knowledge about their biochemical properties. The analysis and research of this rich genetic source provides a precious basis for the advancing biotechnological production of an almost endless number of valuable natural metabolites. Three annotated terpene synthases from the little investigated Basidiomycota Coniophora puteana were studied in this work. For biochemical characterization, the heterologous expression in E. coli was conducted leading to the identification of two sesquiterpene synthases capable of the highly selective generation of β-copaene and cubebol. These compounds are commercially used as food and flavor additives. The new enzymes show the highest reported product selectivity for their main compounds and therefore represent the first exclusive synthases for β-copaene (62% product selectivity) and cubebol (75% product selectivity) generation. In combination with an optimized heterologous microbial production system, we obtained product titers of 215 mg/L β-copaene and 497 mg/L cubebol. The reported product selectivity and our generated terpene titers exceed all published biotechnological data regarding the production of β-copaene and cubebol. This represents a promising and economic alternative to extraction from natural plant sources and the associated complex product purification.

Abstract: The total synthesis of cubebane-type sesquiterpenoids, i.e.α- and β-cubebenes (II) and (III), and cubebol (I), from (–)-trans-caran-2-one (IX), has been accomplished. Pyrolytic cleavage of carane-2-spiro-2′-tetrahydrofuran-5′-one (XII)(having a trans-carane structure) led to methyl 3-(trans-p-mentha-2,8-dien-2-yl)propionate (XV), which was converted into the corresponding diazo-ketone (XVI). Copper-catalysed decomposition of the diazo-ketone resulted in the formation of a mixture of intramolecular addition products, one of which, upon hydrogenation, gave trans-7-isopropyl-10-methyltricyclo[4,4,0,01,5]decan-4-one (norcubebanone)(XVIIIa), the key intermediate of this synthesis. Cubebenes and cubebol were synthesised from norcubebanone, and the stereoselective course of the synthesis provided a synthetic proof for the stereochemistry of these sesquiterpenoids.

Abstract: The purpose of this study is to determine the larvicidal activities of ethanolic extracts from leaves, wood, and bark of black heartwood-type Cryptomeria japonica against fourth-instar larvae of mosquitoes Aedes aegypti and Aedes albopictus. Among three ethanolic extracts from C. japonica, wood extract exhibited the best larvicidal activity against A. aegypti and A. albopictus with LC50 values of 63.2 and 93.8 μg/ml, respectively. Four major compounds, including ferruginol, epi-cubebol, cubebol, and isopimarol, were isolated from wood extract, and it was demonstrated that cubebol exhibited the best activity against A. aegypti and A. albopictus with LC50 values of 60.1 and 50.0 μg/ml, respectively. Our findings showed that the wood extract and cubebol from C. japonica have good potential as a source for natural larvicides.