Monoterpenes cyclic structures

Myreene and ocimene are not arranged in ring structures they are acyclic. However, many monoterpenes link up to form rings or cyclic structures, for example in limonene. 

The sesquiterpenes important in odour terms mostly have complex cyclic structures. The problem of elimination of alcohols to produce olefins on attempted isolation is even more acute with sesquiterpenes than with monoterpenes because of their higher boiling points, which require more vigorous distillation conditions. The sesquiterpenes responsible for the odours of vetiver and patchouli oils have complex structures (21-24), which can only be reached by lengthy and hence uneconomic syntheses. As their names suggest, the vetivones occur in vetiver oil and the patchoulane derivatives in patchouli. 

The enzyme catalyzed reactions that lead to geraniol and farnesol (as their pyrophosphate esters) are mechanistically related to the acid catalyzed dimerization of alkenes discussed m Section 6 21 The reaction of an allylic pyrophosphate or a carbo cation with a source of rr electrons is a recurring theme m terpene biosynthesis and is invoked to explain the origin of more complicated structural types Consider for exam pie the formation of cyclic monoterpenes Neryl pyrophosphate formed by an enzyme catalyzed isomerization of the E double bond m geranyl pyrophosphate has the proper geometry to form a six membered ring via intramolecular attack of the double bond on the allylic pyrophosphate unit... 

The formation of cyclic terpenoids involves intramolecular electrophilic addition, and this can be exemplified by the following monoterpene structures, again with all reactions being enzyme controlled. 

Monoterpenes are formed from two attached isoprene 3 units 2,6-dimethyloc-tane as the simplest skeleton. Thus, they can be acyclic or linear like -myrcene 4, ( )-/l-ocimene 5, (Z)-/l-ocimene 6, and allo-ocimene 7 (Structure 4.3). Or they can be cyclic, meaning ring-forming, such as in the simplest form like p-menthane 8 or p-cymene 9. Monocyclic 8, 9, bicyclic (5-3-carene 10 and tricyclic tricyclene 11 type monoterpenes are found in essential oils [1-4, 6-14, 16-23,38,39, 42, 47, 48]. 

Cineole 42 as well as 1,4-cineole 43 are cyclic ethers (Structure 4.10). All including ascaridol 44 are bicyclic oxygenated monoterpenes. Their formation can be seen in Fig. 4.3. 

Sesquiterpenes are formed by the addition of one more isoprene units to a monoterpene molecule, and thus have the molecular formula C15H24 (see also Fig. 4.2). There are linear, branched or cyclic sesquiterpenes. Sesquiterpenes are unsaturated compounds. Cyclic sesquiterpenes may be monocyclic, bicyclic or tricyclic. They are the most diverse group among the volatile terpenoids [2, 3, 7-11, 13,14, 16, 20-24, 37-39, 49]. The DNP treats sesquiterpenoids in 147 different structural types [37]. Various types of sesquiterpenes (69-109) can also be seen in Structure 4.16. 

Monoterpenes occur in plants in various structural forms some are cyclic while the others are acyclic. They also contain various types of functional group, and depending on their functional groups they can be classified as simple hydrocarbons, alcohols, ketones, aldehydes, acids or phenols. Some examples are cited below. 

The halogenated acyclic marine monoterpenes are often considered to be the biogenetic precursors of the alicyclic monoterpenes that are presented in this section. Many of the preceding algae species also contain cyclic monoterpenes. As was the case in preceding sections only newly characterized compounds are numbered and the reader is referred to the first survey for structures of previously isolated compounds (7). 

The terpenoids form a large and structurally diverse family of natural products derived from C5 isoprene units (Figure 5.1) joined in a head-to-tail fashion. Typical structures contain carbon skeletons represented by (Cs) , and are classified as hemiterpenes (C5), monoterpenes (C10), sesquiterpenes (C15), diterpenes (C2o), sesterterpenes (C25), triterpenes (C30) and tetraterpenes (C40) (Figure 5.2). Higher polymers are encountered in materials such as rubber. Isoprene itself (Figure 5.1) had been characterized as a decomposition product from various natural cyclic hydrocarbons, and was suggested as the fundamental building block for these compounds, also referred to as isoprenoids . Isoprene is produced naturally but is not involved in the formation of... 

Other cyclic monoterpenes, e.g. pinenes, form bridged structures, but the molecular formula is still C10H. ... 

Figure 2. Structures of acyclic precursors and some cyclic monoterpene products.

The enantiomeric separation of some racemic antihistamines and antimalar-ials, namely (+/-)-pheniramine, (+/-)-bromopheniramine, (+/-)-chlorophen-iramine, (+/-)-doxylamine, and (+/-)-chloroquine, were investigated by capillary zone electrophoresis (CZE). The enantiomeric separation of these five compounds was obtained by addition of 7 mM or 1 % (w/v) of sulfated P-cyclo-dextrin to the buffer as a chiral selector. It was found that the type of substituent and degree of substitution on the rim of the cyclodextrin structure played a very important part in enhancing chiral recognition (174). The use of sulfated P-cyclo-dextrin mixtures as chiral additives was evaluated for the chiral resolution of neutral, cyclic, and bicyclic monoterpenes. While there was no resolution of the monoterpene enantiomers with the sulfated P-cyclodextrin, the addition of a-cyclodextrin resulted in mobility differences for the terpenoid enantiomers. Resolution factors of 4-25 were observed. The role of both a-cyclodextrin and sulfated P-cyclodextrin in these separations was discussed (187). The enantiomeric separation of 56 compounds of pharmaceutical interest, including anesthetics, antiarrhythmics, antidepressants, anticonvulsants, antihistamines, antimalarials, relaxants, and broncodilators, was studied. The separations were obtained at pH 3.8 with the anode at the detector end of the capillary. Most of the 40 successfully resolved enantiomers contained a basic functionality and a stereogenic carbon (173). 

There are relatively few sesquiterpenoids which cannot be derived from a farnesyl precursor either directly or indirectly. Recent examples of this rare group are furoventalene (403), the keto-lactone (404), the phenol (405), and the revised structure of humbertiol (406). Proposed biogenetic schemes for these compounds involve the combination of a C o monoterpene unit (either acyclic or cyclic) with a C5 unit (e.g., dimethylallyl pyrophosphate). 

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. 

Although a relatively small number of cyclases must determine the basic structural character of the monoterpenes produced, the great variety of derivatives of each structural type encountered suggests that numerous enzymes must be involved in the secondary transformations of the parent cyclic compounds (Croteau, 1984). As a group, the enzymes catalyzing secondary transformations are not well studied. 

The co-occurrence in many plant species of structurally related monocyclic monoterpenes, such as limonene, terpinolene, and a-terpineol, raises an important question as to whether these compounds arise independently from an acyclic prenyl pyrophosphate precursor or whether such monoterpenes may be formed by sequential modification of a single monocyclic intermediate, such as a-terpineol (Croteau et al., 1973). Cell-free extracts capable of converting acyclic precursors to a-terpineol (Croteau et al., 1973) and to limonene (George-Nascimento and Cori, 1971 Chayet et al., 1977) are available, but until a cell-free system capable of synthesizing several structurally related compounds was obtained, the question of sequential or independent formation could not be resolved. A soluble enzyme preparation from sage leaves was shown to catalyze the conversion of NPP to a number of cyclic monoterpenes, including limonene, terpinolene, a-terpineol, and... 

Representative diterpene structures are shown in Fig. 18. Diterpenes can be classified on a biogenetic basis (Ruzicka et al., 1953 McCrindle and Overton, 1965 Hanson, 1972a). There are a few open-chain diterpenes. Phy-tol, in an ester linkage, is found as a side chain on the chlorophyll molecule. Most diterpenes are cyclic compounds. A few diterpenes are formed by cy-clizations analogous to those involved in the synthesis of cyclohexanoid monoterpenes. The result is a macrocyclic structure such as that of cem-... 

Monoterpenes consist of two 5 C units. They may be open chain or ring structures. The cyclic monoterpenes are further divided into monocyclic and bicyclic systems. 

The same kinds of structural variations that are found among the monoterpenes (open chain or cyclic, one or several ring systems) are also found among the sesquiterpenes, diterpenes, etc. Only the polyterpenes are, without exception, long, open chains of 5 C units linked in series. When one realizes that the terpenoids can also be subject to additional modifications, such as oxidation or reduction, the addition or subtraction of C atoms, it becomes clear that the number of different terpenoids is... 

Like GDP in monoterpenes, FDP in sesquiterpenes can give rise to linear or cyclic compounds. Due to the increased complexity of FDP translated to the length of the side chain and the multiple unsaturation compared to GDP, the number of possible cyclization modes is also increased and a large number of mono-, bi-, and tricyclic diverse structures can be formed catalyzed by specific enzymes collectively termed as... 

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