Caryophyllen derivatives

The similarity between humulene and caryophyllene had not escaped Chapman s notice at the time that he isolated humulene, but as he was nnable to prepare a hydrate, which is one of the easiest of the caryophyllene derivatives to obtain in a pure state, he concluded that the sesquiterpene was not identical with caryophyllene. Eecent work by fiemmler does not tend to establish the identity of the two sesquiterpenes, and unless and until further evidence to the contrary is forthcoming, humvdene may be regarded as a definite chemical individual. 

Caryophyllene, a common constituent of essential oils, was first isolated from clove oil. )S-Caryophyllene [( )-caryophyllene] 105 (Structure 4.30) is the most widely encountered form of caryophyllenes. Caryophyllene derivatives (106-108) are characteristic constituents of most birch oils [49-51]. 

A full paper on the determination of the structure and absolute configuration of the two piscicidal sesquiterpenoids buddledins A (238) and B (239) has now appeared.Buddledin A has also been isolated from another Buddleja species.In addition, the structures of buddledins C (240), D (241), and E (242) have been determined and toxicity tests have shown that the latter two are not piscicidal. Another interesting oxygenated caryophyllene derivative is lych-nopholic acid (243) from Lychnophora affinis Gardn. The structure of this compound has been elucidated by a combination of n.m.r. and X-ray spectral studies. 

Horeau and Kagan5 applied the method to a large number of steroids and found that it led to the correct configurations. It has been applied successfully to terpencs, -2 to caryophyllene derivatives,6 to grayanotoxin-I (1) and related toxins,7 and to sesquiterpene lactones,8 for example (2). 

The total synthesis of caryophyllene and its Z-isomer involved a photochemical [2 + 2] cycloaddition reaction to generate the 4-membered ring and a fragmentation process Helv. Chim. Acta, 1951, 34, 2338) to establish the 9-membered ring. Caryophyllene and various oxygenated derivatives protect plants against insects. 

If these assumptions be correct, there must be at least four natural sesquiterpenes of the caryophyllene character, namely, those represented by formulae (1) and (3), and the terp-caryophyllene and im-caryo-phyllene of Semmler. The most characteristic derivatives of the caryophyllenes are the following —... 

A study of the oxidation products and nitroso-derivatives of caryophyllene, leads Deussen to consider that this sesquiterpene is a naphthalene derivative of the formula—... 

The behaviour of sesquiterpenes, which are less volatile (fi-caryophyllene bp760 262°C), is quite different. Initially their migration from the matrix to the gaseous phase is predominant but beyond a certain temperature, which depends on the boiling point, the migration from the fibre to the gaseous phase predominates. For example, the optimal trapping temperature is lower (40°C) for fi-caryophyllene than for its oxide derivative (60°C). 

By using betulin as substrate, some mechanistic studies were performed and it was demonstrated that these reactions are catalyzed by Brpnsted acid species generated in situ from the hydrolysis of Bi(0Tf)3-.vH20. This process was also applied to other terpenic compounds. The sesquiterpene ( )-caryophyllene oxide originated clov-2-en-9a-ol by a cariophyllene-clovane rearrangement (Scheme 41) whereas 3-oxo- l 8a-olean-28- l 3(3-olide was obtained from oleanonic acid (Scheme 42). With this triterpene derivative, only 28,13(3-lactonization occurred, with inversion of the configuration of the stereocenter at C18 [133],... 

A new elegant stereoselective synthesis of humulene (192) has been achieved by a route (Scheme 22) in which the 11-membered-ring framework [cf. (191)] is produced by cyclization of the 11-allylpalladium complex derived from intermediate (190). Buddledin-A (193), -B (194), and -C (195) are new piscicidal sesquiterpenoids which have recently been isolated from the root bark of Buddleja davidiC The caryophyliane framework of these compounds has been established by spectroscopic data and X-ray analysis of the mono-bromohydrin (196) derived from buddledin A (193). An extension of previous studies on the cyclization of the epoxy-ketone (197) derived from caryophyllene has shown that the base-catalysed cyclization of the isomeric epoxy-ketones (198) and (199) provides compounds... 

Cyclic epoxide derivatives, such as 2,3-epoxy-c/s-pinane 210 [Eq. (5.299)]826 and isomeric caryophyllene diepoxides 211 [Eq. (5.300)],827 undergo varied transformations including ring contraction under similar conditions. 

Collado and co-workers made detailed studies of the chemistry of the sesquiter-penoid caryophyllene and its hydroxylated products including rearrangements in-duced by superacids. They have recently reported novel rearrangements of the sesquiterpenoid panasinsane derivatives 213 to provide three products and interpreted the transformations by the involvement of the common carbocationic intermediate 214 [Eq. (5.304)]. 

Chapters 3 and 4 (familiarity with which is assumed) provide us with powerful techniques and methods to elucidate the structures of organic compounds especially when combined with information derived from IR and mass spectrometry. These NMR methods are collectively referred to as one-dimensional techniques. To extend our capabilities, we turn once more to NMR. We will use four compounds as examples ipsenol (see Chapter 3), caryophyllene oxide (a sesquiterpene epoxide), lactose (a j3-linked disaccharide), and a small peptide (valine-glycine-serine-glutamate, VGSE). The structures of these compounds are shown in Figure 5.1. 

The HMBC for caryophyllene oxide (Figure 5.18) allows us to completely confirm the structure of caryophyllene oxide by giving us the required indirect carbon-carbon connectivities. An analysis of the structure of caryophyllene oxide reveals that there should be 87 cross peaks this number is derived from considering each of the 15 carbon atoms and counting the number of chemical-shift-distinct protons at the a-positions and the number of chemical-shift-distinct protons at the /3-positions. In order to keep track of all of those interactions, one must be methodical indeed. 

Although isocomene (668), mentioned above, is included in this section it is likely that this hydrocarbon, together with modhephene (679), is derived from a caryophyllene-type precursor. Indeed one can conceive of a biogenetic pathway (Scheme 87) which encompasses both these compounds as well as botrydial (681), quadrone (682), and the recently isolated senoxydene (304). " To lend partial credence to this scheme is the fact that the hydrocarbon (680) is a product of acid-catalysed rearrangement of isocaryophyllene (678). ... 

Composition Eugenol (65-85%), methyl eugenol, 1,8-cineole and numerous mono-and sesquiterpene hydrocarbons, e.g. myrcene, p-caryophyllene and humulene [230], The commercially available oils also derive from the leaves and possess a similar composition, whereas the content of methyl eugenol in most cases is higher in the berry oil [231, 232[. For further research results see [233[. 

Aphid Alarm Pheromone. The alarm pheromone of aphids in the subfamily Aphidinae is ( )-P-famesene. The pheromone can be synthesized easily, but it is unstable under field conditions and therefore has limited potential for application. Although many plants produce this volatile chemical constitutively in their essential oil, aphids can differentiate between plant-produced material and aphid-produced material by the presence of other plant-derived terpenes, particularly ( )-caryophyllene, in the volatile blend. 

Naya and Kotake, in an examination of Japanese hop oil, have isolated three humulane-type compounds, viz., humuladienone (161, R = Me), humulenone II (161,R = =CH2), and humulol (162), in addition to the tricyclic diol (163, R = OH), m.p. 207 °C. This diol has already been prepared in two different ways (a) Sutherland et treated humulene (164) with AT-bromosuccini-mide in aqueous acetone and converted the resultant bromohydrin (163, R = Br) to the diol (163, R = OH), m.p. 205—206 °C, by hydrolysis, (b) McKervey and Wright obtained the same diol, m.p. 201—203 °C, by acid-catalysed (20% sulphuric acid) rearrangement of humulene 1,2-epoxide (165), a known natural product. On the basis of these findings and the fact that both caryophyllene (166) and humulene can be derived from the above bromohydrin by two in vitro steps, McKervey and Wright postulated that humulene 1,2-epoxide may be involved in the biosynthesis of the tricyclic diol and caryophyllene. This postulate does not, however, readily accommodate the observed rotations of the relevant... 

Humulene biosynthesis probably involves the intermediacy of a monocyclic carbonium ion or its biological equivalent [c/. (303)] derived from trans,trans-farnesyl pyrophosphate (16), A recent investigation based on this idea has shown that treatment of the ( , )-mesylate (303 Z=OMs) with dime thy laluminium phenoxide provides humulene (304) in excellent yield. The corresponding (Z, )-isomer, when treated with di-isobutylaluminium 2,6-dibutyl-4-methyl-phenoxide, is efficiently converted into germacrene (307) whereas the E,E)-isomer under these conditions provides a mixture (2 1) of humulene (304) and germacrene A (305). Monohydroboration-oxidation of caryophyllene... 

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