Thujaplicins

Arizona yielded (3-thujaplicin and nootkatin as major components along with lesser amounts of y-thujaplicin [241] and p-thujaplicinol. At a higher taxonomic level, two subspecies of C bakeri Jepson (subsp. bakeri and subsp. mattewsii Wolf), gave identical profiles consisting of P-thujaplicin and nootkatin. 

This electroreductive alkylation is successfully applied to the synthesis of /1-thujaplicin. 

The mechanism of this rearrangement has been studied in details by Bartlett85). And this strategy has been applied to the synthesis of P-dolabrin (255)86) as well as P-thujaplicin (257)87). 

Cycloheptanes.— The C-1—C-2 bond in -y-thujaplicin is essentially single, Co"-/3-thujaplicin-amine complexes have been described, and thermodynamic data on the U -/3-thujaplicin complex have been calculated. The biomimetic cyclization of the silyl enol ether (191) to karahanaenone (192), using methyl-aluminium bis(trifluoroacetate) is almost quantitative (192) is also synthesized by thermolysis followed by desilylation of the silyl enol ether (193) which is readily available from l-bromo-2-methyl-2-vinylcyclopropane and isobutyraldehyde. Dehalogenation of 3-bromo-l-iodo-3-methylbutan-2-one with Zn-Cu couple on alumina in the presence of isoprene yields (192) and minor amounts of the isomers (194) and (195) however, dehalogenation with Fc2(CO)9 favours (195). Acetolysis of karahanaenol tosylate yields anticipated p-menthane derivatives and no filifolene. ... 

The substituted cycloheptane monoterpenes, also called tropones. Eu-carvone 60, nezukone (4-isopropyl-2,4,6-cycloheptatrienone) 61 and y-thujaplicin 62 (Structure 4.14) most probably arise by an unknown ring expansion of the cyclohexane skeleton. 

The bicyclic ketone (44), obtained from the Fe2(CO)9-promoted [3 + 4] cycloaddition reaction of a,a,a, a -tetrabromoacetone and 2-isopropylfuran followed by Zn-Cu couple reduction, has been converted to the naturally occurring troponoid, /3-thujaplicin (46) (75JOC806). Hydrogenation of (44), ether cleavage, bromination and dehydrobromination gave the tropone (45), an intermediate easily converted into the tropolone (46) by a standard procedure (Scheme 10). A related [3 + 4] cycloaddition reaction of oxyallyl metallic with furan has been used to assemble the antibiotic C-nucleosides (78JA2561). 

The tropolones make up a very interesting class of nonbenzenoid aromatic compound that was discovered first in several quite different kinds of natural products. As one example, the substance called /3-thujaplicin or hinokitiol has been isolated from the oil of the Formosan cedar and is 4-isopropyltropolone ... 

Franck-Neumann has reported the synthesis of naturally occurring tropolones -thujaplicin and 3-do-labrin via the readily available [Fe(tropone)(CO)3] as shown in Scheme 23.43 A key step in the sequence is regiospecific acetylation of the [Fe(tropone)(CO)3] complex, a reaction which cannot be carried out on... 

Iron carbonyls also mediate the cycloaddition reaction of allyl equivalents and dienes. In the presence of nonacarbonyldiiron a,a -dihaloketones and 1,3-dienes provide cycloheptenes (Scheme 1.5) [14,15]. Two initial dehalogenation steps afford a reactive oxoallyliron complex which undergoes a thermally allowed concerted [4 + 31-cycloaddition with 1,3-dienes. The 1,3-diene system can be incorporated in cyclic or heterocyclic systems (furans, cyclopentadienes and, less frequently, pyrroles). Noyori and coworkers applied this strategy to natural product synthesis, e.g. a-thujaplicin and P-thujaplicin [14, 16]. 

Fig. 5-8. Examples of phenolic extractives and related constituents. 1, Gallic acid 2, ellagic acid 3, chrysin 4, taxifolin 5, catechin 6, genistein 7, plicatic acid 8, pinoresinol 9, conidendrin 10, pinosylvin 11, /3-thujaplicin.

The iron carbonyl-promoted [3 + 4] cycloaddition of bromo-ketones to. 1,3-dienes provides a convenient way, via 2-oxyallyIs, of synthesizing tropones and hence thujaplicins. The synthesis of nezukone (154 X = H)253 has been reported from a,a,a, a -tetrabromoacetone and 3-isopropylfuran. Similarly, from 2-isopropylfuran, /3-thujaplicin (154 X = OH) has been synthesized from the corresponding tropone by known methods, and a-thujaplicin synthesis requires isopropyl substitution in the ketone moiety.254 Karahanaenone (155) is a minor product from pyrolysis of the benzoate (156).149... 

Measurement of activation energy and entropy has not distinguished between antara-antara Cope rearrangement and other concerted processes in the photochemical rearrangement of y-thujaplicin O-methyl ether to the bicyclohep-tadienones (157) and (158).255 The hexatriene-cyclohexadiene disrotatory elec-... 

Tropolone monoterpenes include the antifungals (1- and y-thujaplicin (4- and 5-isopropyltropolones, respectively, tropolone being 2-hydroxycyloheptatrienone (C7)). The antioxidant 3- thujaplicin (hinokitiol) is an inhibitor of 5-, 12- and 15-LOXs. 

Thujaplicin (= Hinokitiol Thuja plicata, Cupressus sargentii, 5-LOX, 12-LOX, SLOX,... 

Oxabicyclo[3.2.1]oct-6-en-3-ones (75) are also readily transformed to tropones (97) or y-tropolones (98) in a few steps. The tricyclic adduct (75 R = (CH2)9) can be readily converted to troponophane (101). Successful use of tetrabromoacetone and tribromo derivatives of methyl alkyl ketones in these reactions opens a new route to various naturally occurring troponoid compounds, viz. nezukone (102), a-thujaplicin (103) and hinokitiol 0-thujaplicin) (104), = respectively (Scheme 24). 

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