Caryophyllene, structure

Caryophyllenes are a class of sesquiterpenes that protect plants against insects, and have a quite unusual structure a four membered-ring fused to a medium-sized ring of nine carbon atoms. There are two isomers which only differ in the configuration of an endocyclic double bond the so-called a-caryophyllene ( -isomer) (la) and the corresponding (Z)-isomer the P- or isocaryophyllene (lb). 

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]. 

Humulene 109 (Structure 4.31) is isomeric with caryophyllene. First isolated from hops oil (Humulus lupulus), it is a common constituent of essential oils. 

Chemical structure-activity relationships suggested that phenolic monoter-penes (thymol, methyleugenol) seemed to be the most active, followed by alcohols (terpineol) and other oxigenated monoterpenes (1,8-cineole) [225, 229, 230]. Within the monoterpenes, -pinene was more active than a-pinene [226], and a-pinene was more active than caryophyllene and myrcene [234]. 

In or d e r to make data correlation practicable in supercritical carbon dioxide extraction, it is convenient to represent each major chemical classification by a single compound. Each select compound should have available good vapor pressure data and should be a predominant constituent in its group with regard to structure and concentration. For correlation purposes, we selected liraonene, geranial, and 3-caryophyllene. Their structures are shown in Figure 1. 

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. 

Before undertaking detailed discussions of H— H COSY and the structure of ipsenol, there is one further experimental refinement that decreases the clutter along the diagonal. Although we can interpret this spectrum without this refinement, there are instances (i.e., caryophyllene oxide) when this improvement makes a great deal of difference. 

The DQF-COSY spectrum of caryophyllene oxide can be found in Figure 5.16. The problem here is that there is no good entry point. The previous statement is not trivial. Without an entry point, it is impossible to relate the many obvious correlations (drawn in for convenience) that we see to a structural formula. Our approach therefore will be to record some of the correlations that we do see and wait until we have other information (i.e., HMQC) before we try to translate these correlations into a structure. 

FIGURE 5.15 The H, 13C, and DEPT spectra for caryophyllene oxide. The numbering for this structure is used in the text. 

H-l shows coupling to both C-2 protons at 1.45 and 1.63 ppm. The interaction is weak between H-l and H-2 at 1.63 ppm. Both C-2 protons are coupled to both C-3 protons at 0.95 and 2.06 ppm and the appropriate cross peaks can be found. Thus, we have shown indirect connectivities from C-10 through C-9, C-l, and C-2 all the way to C-3. The HMQC has been invaluable in our interpretation. However, many questions still remain. We neither have correlations to the three quaternary carbons nor to the three methyl groups. The HMQC and the COSY together support the structure for caryophyllene oxide, but they do not preclude other possible structures. 

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. 

There are two protons on C-2, which are labeled H-2 and H-2 these protons have different chemical shifts, yet we expect them to act much the same way in the HMBC. Thus, we have a useful independent check of our HMBC assignments for each pair of diastereotopic protons in caryophyllene oxide. For H-2 at 1.45 ppm, we have the same five correlations that we have for H-2 at 1.63 ppm. As we study the spectrum and the table more closely, we find that we have exquisitely detailed structural information that can be deciphered with a methodical approach. 

The common theme so far in our correlation experiments has been to allow spins to evolve during q under the influence of directly coupled nuclear spins. We have seen the power of COSY, HMQC, HMBC, and INADEQUATE to provide us with detailed structural information for ipsenol, caryophyllene oxide, and lactose. In this section, we will develop another method for showing correlations and apply it to molecules with distinct, isolated proton spin systems such as carbohydrates, peptides, and nucleic acids. 

Caryophyllene nitrosite is made from an extract of ginger and purified to give blue needle-like crystals.51 When dissolved it decomposes by absorption of light in a narrow band at 6,800 A giving nitrogen gas and a colorless solution. It is decomposed also by heating to about 100°. Its exact structure is unknown. 

Pestalotiopsin A and 6-epitaedolidol are structurally related caryophyllene-type sesquiterpenes. In 2003, Procter reported the use of a Sml2-mediated 4-exo-trig carbonyl-alkene cyclisation to construct the core of pestalotiopsin A.57 Treatment of cyclisation substrate 33 with Sml2 in THF, MeOH and 2,2,2-trifluoroethanol gave cyclobutanol products 34 and 35 in good yield and with moderate diastereoselectivity. The major diastereoisomer is believed to arise from a cyclisation in which coordination to the silyl ether group directs addition of the ketyl radical anion to the alkene (Scheme 7.17).57... 

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. 

Using the most active catalyst (CoNaY) we have studied the oxidation of olefins of different structure and size of molecules, including a number of natural terpenes, namely, (+)-a-pinene (1), (+)-3-carene (2), (-)-caryophyllene (3) and dipentene (4). We have found that even acid-sensitive epoxides that are known to be prone to ring cleavage (caryophyllene epoxide, for example) can be obtained with high-to-exceUent selectivity (Table 2). It is noteworthy that neither allylic oxidation nor overoxidation occurs in the systems studied. Diolefins give mono-... 

Se8qulterpenold semlochemlcals. The aphid-repellent effect of Type B trichomes of S. berthaultii (25) appears to be due to the presence of sesquiterpenes (22). Three major components, identified by GC-MS, were B-caryophyllene, B -cubebene and A-cadinene. E-B-farnesene was also identified, but was a minor component. GC-MS of the other major components in Type B trichome exudate indicated sesquiterpenold structures, but these have not been identified. 

The structures of two of the four isomeric photo-products of caryophyllene have been determined by X-ray analysis.These are photocaryophyllene A (158, R = a-Me) and photocaryophyllene D (158, R = -Me). Two oxidatively... 

Marine organisms have provided the source of a number of unusual diterpenoid skeleta. Obtusadiol (115) is a bromo-diterpenoid which has been obtained from the red alga Laurencia obtusa. Its structure followed from chemical degradation including a facile ring contraction of the bromohydrin. A group of prenylated caryophyllenes , xeniaphyllenol (116), its 4,5-epoxide, and an enol-ether related to xenicin, ° xeniculin (117), have been found in Xenia macro-... 

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