Monoterpenes, cyclic

The three most important cyclic monoterpenoids are 1-menthol, 1-carvone and a-terpineol (including its esters). 1-Menthol occurs in a number of mint oils and is used not only for its minty odour, but also, and more importantly, for its physiological cooling effect. Its chemistry is of such interest and significance that it warrants a section of its own, which will be found at the end of this one. 

During processing of turpentine and other terpene sources, often a variety of acid-catalysed reactions and aerial oxidations occur. / -Cymene is often produced as a result of these processes since it is one of the most thermodynamically stable of terpenoid structures, ft does occur in essential oils and fragrances, but its main uses are as a thermally stable heat transfer fluid and as a precursor for musks (see Section 4.3). 

With respect to the biosyntheses of menthane-type monoterpenes, the menthyl cation C can either lose a proton resulting in the formation of Umonene (16), or it may be directly attacked by H O to give a-terpineol (17), which can 

Pinane Camphane Isocamphane Fenchane type type type type 

SCHEME 6.4 Formation of the linchpin intermediate C and parent skeletons of different cyclic monoterpenes. 

Both intermediates can then liberate a proton to obtain the isomeric monocyclic terpenes 19-22 or can be trapped by addition of H O, which, for example, can result in the formation of terpinen-4-ol (23). 

SCHEME 6.5 Exemplified biosynthetic pathways toward monocyclic monoterpenes and advanced (bicyclic) derivatives thereof. 

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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... 

Cyclical monoterpenes such as limonene have also been used as substrate for the production of valuable products. A good example is the conversion of limonene to a-terpineol by Cladosporium sp. Thus,... 

Cyclic method, selenium and tellurium purification via, 22 86 Cyclic molecules, synthetic, 24 35 Cyclic monomers, ring-opening polymerization of, 14 271 Cyclic monoterpenes, aroma chemicals,... 

Burbott, A. ]., R. Croteau, W. E. Shine, and W. D. Loomis. Biosynthesis of cyclic monoterpenes by cell freee extracts of Mentha piperita. Int Congr Essent Oils (PAP) 6 Allured Publ Corp Oak Park, 111 1974 17 1. 

Aida, M., Hano, Y., and Nomura, T., Constituents of the Moraceae plants. 26. Eicusins A and B, two new cyclic-monoterpene-substituted isoflavones from Ficus septica Barm. E., Heterocycles, 41, 2761, 1995. 

As in the case of the cyclic monoterpene hydrocarbons, a number of the cyclic sesquiterpenes are used as starting materials in the synthesis of fragrance and flavor substances or for the reconstitution of essential oils. 

Table VII shows the Increase In cytochrome P-450 content In mlcrosomes from southern armyworm larval midguts resulting from dietary exposure to several cyclic monoterpenes ( ). It also shows a closely corresponding Increase In the rate of NADPH oxidation when pyrethrum Is the substrate (R) being oxidised. The microsomal cytochrome P-450 system Is arranged as outlined In Figure 6, consisting of a terminal heme-lron protein that In the oxidised (Fe3+) state binds the substrate (R). The complex undergoes two reductions during which bound molecular oxygen Is converted to free radical species, one of which Is Inserted In the substrate molecule, and the other one forms water. The reductions...

Cyclic monoterpenes can be classified in three subgroups according their ring size such as ... 

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). 

Cyclic monoterpenes increase the penetration of hydrophilic and lipophilic drugs [125-129]. Cornwell et al. found remarkable penetration enhancement of 5-fluorouracil after pretreatment with the noncyclic terpenes nerolidol, famesol,... 

Stierle, D. B. and Sims, J. J., Polyhalogenated cyclic monoterpenes from the red alga Plocamium cartilagineum of Antarctica, Tetrahedron, 35, 1261, 1979. 

Acyclic monoterpene alcohols are present in many essential oils and can be isolated by distillation, although nowadays, they are often synthesized from other sources. Geraniol and linalool (Fig. 7) are the most important monoterpene alcohols and together with nerol are the primary products in terpene biosynthesis [44]. a-Terpineol is a frequently used cyclic monoterpene alcohol in the fragrancing industry because of its typical lilac odor and is also partly responsible for the typical... 

In a process that is quite similar to the formation of the cyclic monoterpenes, isomerization about the double bond of farnesyl pyrophosphate, followed by carbocation... 

Marongiu, B., Piras, A. and Porcedda, S. (2004) Cyclic monoterpene extract from cardamom oil as a skin permeation enhancer for indomethacin in vitro and in vivo studies. 1. journal of Agriculture and Food Chemistry 52(20), 6278-6282. 

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

Examples of monoterpenes include the linear aldehyde citral, which is found in many essential oils, and the (cis) alcohol geraniol, a major component of oil of geranium. Cyclic monoterpenes include limonene, menthol, pinene, camphor, and carvone, major components of lemon oil, mint oil, turpentine, camphor oil, and caraway oil, respectively. Sesquiterpenes include farnesol, a component of rose oil, and bisabolene, a component of Bisabol myrrh. The diterpenes include phytol, a component of chlorophyll, and vita-... 

Non-cyclic monoterpenes are unsaturated, pleasant-smelling, C]q aliphatic compounds including aldehydes such as citronellal and citral (lemon-scented) the sweet-rose... 

Mono- and bi-cyclic monoterpenes containing sites of unsaturation tend to be hydroxylated at the allylic position, (more examples of allylic hydroxylation are discussed in Section 1.4.5.2) with regio-isomers occurring if more than one allylic position is accessible. Some illustrative examples of reported hydroxylations are shown in Scheme 10. " The hydroxylation of 1,4-cineole (42) is illustrative of the enantioselectivity that may be achieved in such transformations. Bacillus cereus gives a 1 7 mixture of 2R)-exo- and (25)-e/tdo-monohydroxy-1,4-cineole, both with essentially 100% enantiomeric purity. ... 

In the synthesis of a-terpineol or limonene, for example, geranyl pyrophosphate isomerizes at one double bond to form neiyl pyrophosphate, a stereoisomer (Step [1] in the following reaction sequence). Neryl pyrophosphate then cyclizes to a 3° carbocation by intramolecular attack (Steps [2]-[3]). Nucleophilic attack of water on this carbocation yields a-terpineol (Step [4]) or loss of a proton yields limonene (Step [5]). Both products are cyclic monoterpenes. 

As soon as we start to make typical cyclic monoterpenes from geranyl pyrophosphate we run into a snag. We cannot cycllze geranyl pyrophosphate because It has a trans double bond We could cyclize the cis compound (neryl pyrophosphate), and It used to be thought that this was formed from the trans compound as an Intermediate. 

Quite interesting and indicative in respect to the authentication of the compounds may also be their oxygen isotope characteristics. OH-groups of acyclic and of some mono-cyclic monoterpenes are introduced as OH" from water, substituting the pyrophosphate functionality of the biosynthetic precursor. This hydrolysis is probably accompanied by a kinetic isotope effect, from where a relative low 8 Q-value is to be expected. The 8 0-value of synthetic analogues will depend on the oxygen source... 

Cyclization of an allylic pyrophosphate is a key step in the biosynthesis of most monoterpenes. Early hypotheses concerning the nature of the acyclic precursor and the cyclization process are first described, and chemical models for the cyclization presented. Following a review of several representative cyclase enzymes and the reactions that they catalyze, a series of stereochemical and mechanistic experiments with partially purified cyclases are reported. The results of these studies have allowed a detailed description of events at the active site and the formulation of a unified stereochemical scheme for the multistep isomerization-cyclization reaction by which the universal precursor geranyl pyrophosphate is transformed to cyclic monoterpenes. 

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