Cubebol

An electrochemical procedure for the replacementofcarboxyl function by an acetoxy group at the C-2 carbon atom of a tricyclo[4.4.0.01,s]decan-4-one system has been realized 90 . The procedure is utilized as the key step for the synthesis of cubebol 114... 

The typical secondary metabolites of soft corals are diterpenoids, although some species also produce sesquiterpenoids. The sesquiterpene portion of furoquinol (Structure 2.102) is labeled by [2-3H]mevalonolactone in Sinularia capillosa,m while Heteroxenia sp. converts acetate and meva-lonate into cubebol (Structure 2.103) and clavukerin A (Structure 2.104).188 In contrast, acetate is used for cetyl palmitate synthesis in Alcyonium molle, but not for de novo diterpene biosynthesis.188... 

About 20 oxygenated sesquiterpenes have been identified from pepper oil. They are 5,10(15)-cadinen-4-ol,caryophylla-3(12), 7(15)-dien-4-P-ol, caryophylla-2,7(15)-dien-4- 3-ol, caryophylla-2,7(15)-dien-4-ol, P-caryophellene alcohol, caryophyllene ketone, caryophellene oxide, epoxy-dihydrocaryophellene, cis-nero-lidol, 4,10,10-trimethyl-7-methylene bicycle-(6.2.0) decane-4-carboxaldehyde, cubenol, epi-cubenol, viridiflorol, a- and P-bisabolols, cubebol, elemol and y-eudesmol. 

The first mechanistic pathway in equation (73) is probably followed when n = 2, as shown in a key Pt(ll)-catalyzed cychzation for the synthesis of (—)-a-cubene and (—)-cubebol. This was estabhshed on the basis of observation that the configuration at the stereogenic center carrying the acetate translates into the configuration of the final products, which excluded planarization of the intermediate. (—)-Cubebol was also synthesized using a similar cychzation catalyzed by Pt(n), Au(l), or Cu(l). A cyclization of this type with AuCb was used for the synthesis of 2-sesquicarene and related compounds (equation 75). ... 

An alternative synthesis of cubebol (175) is very similar to that previously reported by another research group cf. Vol. 4, p. 102) and utilizes the same intramolecular... 

Additional remark The not sharp tasting fruits of another pepper species, cubeb (R cubeba L.), are also used for seasoning purposes (ingredient of curry). Apart from starch, protein and fatty oil, they contain 6-11% essential oil with 5-cadinene, P-cubebene, a-copaene, cubebol and germacrene D as main components. Origin and Output Indonesia (essential oil less than 1 t). 

Yoshikoshi et al. have published the complete details of their syntheses of the cubebenes and cubebol. 

TERP 4-Cadainene Cadmane-4 (-)-germacrene D (-)-cubenol 4-epi-cubebol [60]. 

Cubebol (295) occurs in a number of essential oUs. The richest source is Cubeb Oil Piper cubeba) in which it is present at 10% (350). Patent applications have been filed by Firmenich claiming it as a cooling and refreshing agent, in combination with other cooling agents [351-353]. 

Sabinene, /S-elemene, /S-caryophyllene, e/)/-cubebol, cubebol Cuminaldehyde, p-mentha-1,4-dien-7-al,... 

The Rautenstrauch rearrangement has been used in a number of total syntheses of polycyclic terpenoids. Fehr and Fiirstner have disclosed closely related approaches in the total synthesis of (-)-cubebol (Scheme 5.24), where the cycloisomerization of enantioenriched propargyl pivalates 66 occurs with good chirality transfer to give 67 in 77% yield [79-81]. Using similar strategies, various terpenoids derivatives have efficiently been obtained [80, 82]. 

Scheme 5.24 Total synthesis of (—)-cubebol featuring a Rautenstrauch rearrangement.

Fehr, C., Galindo, J. (2006). Synthesis of (—)-cubebol by face-selective platinum-, gold-, or copper-catalyzed cycloisomerization evidence for chirality transfer. Angewandte Chemie - International Edition, 45, 2901-2904. 

Fiirstner, A., Hannen, P. (2006). Platinum- and gold-catalyzed rearrangement reactions of propargyl acetates total syntheses of (—)-alpha-cubebene, (—)-cubebol, sesquicarene and related terpenes. Chemistry - A European Journal, 12, 3006-3019. 

Cubebol (91), a-cubebene (92), and p-cubebene (93) are isolated Irom the berries of Piper cubeba [79]. Due to its pronounced cooling effects, cubebol was patented in 2001 as a refieshing agent for applications in various products ranging... 

SCHEME 7.57 Key cycloisomerization reaction for the total synthesis of cubebol natural products. ... 

Fiirstner and Hannen reported the application of PtCl -catalyzed cycloisomerization of 1,5-enyne 225 to efficient synthesis of (-)-Cubebol 227, (-)-a Cubebene 228 and (-)-P Cubebene 229 through the same intermediate 226 (Scheme 7.45) [95]. 

SCHEME 7.45 Total synthesis of (-)Cubebol, (-)-a Cubebene and (-)-P Cubebene. 

This reaction constitutes a robust method that has found application in natural product synthesis. The total syntheses of (-)-a-cubebene, (-)-cubebol, sesquicarene, and... 

Epoxymuurolane DUophus fasciola Amico et al., 1979 Cubebol Dictyopteris divaricata Suzuki et al., 1990... 

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