Thujane monoterpene

Thujane monoterpenes are based on the bicyclic (G3 C5) monoterpene thujane and include umbellone (thujan-2-one) and the neuroactives a-thujone and 3-thujone (thujan-3-one isomers) that can cause convulsions. Thujones are GABA(A) receptor antagonists and are the active constituents in oil of wormwood from Artemisia absinthium (Asteraceae) used in the alcoholic drink absinthe that was eventually banned because of its deleterious neurotoxic effects. 

Fig. 19.9. R-oposed pathway for the biosynthesis of C-3-oxygenated thujane monoterpenes from sabinene (modified from Croteau, 1984 modified and used with permission of the copyright owner, Marcel Dekker, Inc., New York).

Croteau R (1992) Biosynthesis of thujane monoterpenes. In Hopp R,Mori K (eds) Recent developments in flavor and fragrance chemistry. VCH, Weinheim Germany, p 263 Croteau R (1992) Monoterpene biosynthesis cyclization of geranyl pyrophosphate to (+)-sabinene. In Teranishi R, Takeoka GR, Guntert M (eds) Flavor precursors thermal and enzymatic conversions. American Chemical Society, Washington DC, ACS Symp Series 490, p 8... 

Thujane-type monoterpenes, unusual monoterpenes with a cyclopropane ring in a bicyclo[3.1.0] skeleton, are formed from the terpinen-4-yl cation directly or via the sabinyl cation. Important members include a-thujene 52, sa-binene 53, the cis isomer 54 of sabinene hydrate, sabinol 55, sabinylacetate 56, a-thujone 57, -thujone 58 and isothujanol 59 (Structure 4.13). 

Additional chemical diversity of monoterpenes is apparent from the natural occurrence of their bicyclic analogs that bear cyclopropane (carane and thujane types), cyclobutane (pinane type), and cyclopentane (camphene/bornane, isoeamphane and fenchone types) rings (Figs. 6 and 7). The carane type of bicyclic monoterpenoids in plants is represented by (+)-3-carene... 

C(4) to C(8) (equation 3). The in vivo labeling patterns of i/-3-thujone (48), sabinene (55) and other thujane-type monoterpenes derived from [2- C]mevalonic acid (56a) in various species are consistent with Ruzicka s hypothesis in which the double bond of the... 

Thus, it has been shown that the biogenesis of the thujane series of monoterpenes requires two 1,2-hydride shifts in the interconversions of the ions derived from a-terpinol and terpinen-4-... 

C,oH,jO, Mr 152.24, oil with a menthol-like odor. Bi-cyclic monoterpene ketones with the thujane structure occurring in two C-4-epimeric forms in nature i SAR,5R) -)-a-T, bp. 83.8-84.1 °C (17 hPa), [a]o -19.2° (neat), (15, 4S,5/ )(+)-)S-T., bp. 85.7 -86.2°C (17 hPa), [a]o +72.5° (neat). Not only the names a-and jS-thuJone but also thujone and isothujone are sometimes used incorrectly in the literature. T. are potent neurotoxins, cause epileptic seizures, and can lead to severe psychic damage. It is not yet known if both epimers exhibit the same biological effects. Occurrence Very widely distributed in the essential oils of Asteraceae, Cupressaceae, Lamiaceae, Pina-ceae species. Thuja oil (Thuja occidentalis, Cupressaceae) contains 40% (-)-a-T. and tansy oil (Tanace-tum vulgare, Asteraceae) 58% (+)-/S-T. 

C oH s, Mr 136.24, oil. Unsaturated bicyclic monoterpenes with the thujane structure occurring in both enantiomeric forms. 

Bicyclic cyclopropanes carane and thujane, bicyclic cyclobutane pinane, and bi-cyclo[2.2.1]heptanes such as camphane, isocamphane and fenchane are the most important skeletons of naturally occurring bicyclic monoterpenes... 

Most common bicyclic monoterpenes are members of the pinane, bor-nane, or thujane families, while members of the fenchane and carane series are less widely distributed. 

The most common members of the thujane family of monoterpenes are the... 

An important precursor of (-)-perrillyl aldehyde (periUal) is (-)-perillyl alcohol. Fenchol (also known as a-fenchyl alcohol or fenchan-2-ol, 8-20) is a bicyclic monoterpenic alcohol occurring as a minor component in citrus, fennel and sage essential oils. Another common compound is the bicyclic alcohol thujan-4-ol (sabinene hydrate), which occurs at a high level in the marjoram essential oil (see Table 8.32, later). Borneol (bornan-2-ol) is a component of camphor oils Cinnamomum camphora, Lauraceae). Trivial and systematic names of selected monoterpenic alcohols are listed in Table 8.6. 

Alternatively, the pathway toward the cyclopropane-containing thujane-type monoterpenes utilizes the terpinen-4-yl cation E, which can form the thujyl cation F via a t-cation cycliza-tion. Subsequent deprotonation then gives the bicyclic sabi-nene (42), which can also be further metabolized to thujone (43) (Scheme 6.8). 

SCHEME 6 Biosynthetic pathways toward carane- and thujane-type monoterpenes. 

The biogenesis of the thujane family of monoterpenes involves a homoallylic cyclization of the 4-terpinenyl carbonium ion (36) to a cyclopropylcarbinyl cation. Tracer experiments seem to be in accord with this scheme (56, 100). 

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