Monoterpenes

Many polyhalogenated monoterpenes have potent biological activity (7). In addition to cytotoxic activity, several compounds display insect repellent and antifeedant activity, and selective insect cell toxicity (480). To acquire sufficient quantities of these and other target metabolites for biological evaluation, the laboratory cultivation of marine algae - bioprocess engineering - is under intense exploration (481 483). 

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 pyran metabolites, pantopyranoids A-C (231-233), have been isolated from the Antarctic alga Pantoneura plocamioides (494). This seaweed and Plocamium cartilagineum contain plocamiopyranoid (234) and 235, and pantoneurines A (236) and B (237) (496). The Pakistani herb Mentha longifolia has yielded the novel chlorinated menthone longifone 238 (497), one of the few known terrestrial halogenated monoterpenes. 

The relationship of cyclic monoterpenes, e.g. 4.3) and 4.53), to geranyl pyrophosphate 4.41) is an obvious one. The tram double bond in 4.41) means that 4.41) cannot cyclize directly to give monoterpenes such as 4.53), and neryl pyrophosphate 4.51) may be more directly involved in biosynthesis. [A cell-free preparation of Mentha piperita has been obtained which will catalyse the conversion of neryl pyrophosphate 4.51) into a-terpineol 4.3) [65].] The conversion of geraniol 4.2) into nerol 4.49) is well known and involves a stereospecific proton removal from C-1 loss of a proton indicates that the aldehyde 4.50) is involved in double-bond isomerization [66]. Initiation of cyclic monoterpene formation can be seen as 

The three most important cyclic monoterpenes are L-menthol, l-carvone and a-terpineol (including its esters). L-Menthol occurs in a number of mint oils and is used not only for its minty odour, but also, 

The first step involves addition of the nitrosyl cation to D-limonene. This cation can be obtained by heterolysis of nitrosyl chloride, but in practice it is more convenient to generate it by cleavage of isopropyl nitrite using hydrochloric acid. Isopropyl nitrite is easily prepared from 

Monocyclic monoterpene hydrocarbons occur in many essential oils and their by-products. They have relatively weak odours, although some add dryness and green notes to the oils containing them. This is particularly so for lime and petitgrain. D-Limonene (1) occurs in citrus oils whereas the L-isomer is found in pine. If limonene or other terpenes break down during processing to produce isoprene, then racemic limonene, dipentene, is found in the product as a result of the Diels-Alder reaction. Terpinolene (2) is the dehydration product of a-terpineol and so it is often present as an artefact. a-Phellandrene (3) occurs in eucalyptus oil. Since it is a 1,3-diene, it is an obvious precursor for Diels-Alder reactions and a number of speciality ingredients are 

Many oxygenated monocarbocyclic monoterpenes are of use to the flavour and fragrance industry. Some are extracted from natural sources, and others are prepared from the major members of the family, usually by straightforward functional group interconversions. 

Carveol (5) is one of the minor components responsible for the odour of spearmint, and is easily prepared by reduction of carvone. Isopulegol (6) is prepared from citronellal, as discussed in the section on menthol below, and is a precursor to other materials in the group. The phenols carvacrol (7) and thymol (8) are important in some herbal odour types, but the major use for thymol is as a precursor for menthol q.v. Piperitone (9) and pulegone (10) are strong minty odorants, the latter being the major component of pennyroyal oil. 1,8-Cineole (11) is the major component of such eucalyptus oils as Eucalyptus globulus. These oils are inexpensive and so there is no need to prepare cineole synthetically. Menthofuran (12) is an important minor component of mint oils and can be prepared from pulegone. 

From their carbon skeletons terpenes can be seen as isoprene (C5) oligomers. Terpenes are classified according to their number of isoprene units as monoterpenes (C10), sesquiterpenes (Q5), diterpenes (C2o), etc. /1-Carotene (1) is a tetrater-pene. 

Many oxygenated monoterpenes (alcohols, carbonyl compounds, esters) serve as fragrances. Here inexpensive natural starting compounds are a-pinene (4), /1-pinene (5) and limonene (6), with production volumes of about 18000, 12 000, and 30000 t a-1, respectively. 

The two pinenes are obtained from Crude Sulfate Turpentine (CST), which is a side product of the sulfate cellulose process from pine trees. Limonene is present in orange and lemon peels [which provide different enantiomers/ )], and is a cheap by-product of the citrus industry. 

Heteropoly acids such as H3PW12O40 (PW) are good catalysts for the hydration of limonene and other monoterpenes. PWs can be used as homogeneous catalysts in solution or supported on, for example, silica or MCM-41 materials. In aqueous acetic acid limonene gives, in the presence of PW, mainly a-terpineol (7) and a-terpinyl acetate (8) [17]. 

A quite different limonene conversion is the dehydrogenation into p-cymene, thus giving a green aromatic. Pd-catalysts give yields of 95% [18]. p-Cymene can be oxidized to the hydroperoxide, which can be rearranged to p-cresol, a valuable chemical. 

Archer, B. L. Polyisoprene. In Encyclopedia of Plant Physiology, New Series, Vol. 8, Secondary Plant Products (E. A. Bell, B. V. Charlwood, eds.), 309-327. Springer, Berlin-Heidelberg-New York 1980 

Cordell, G. A. The sesterterpenes, a rare group of natural products. Prog. Phytochem. 4, 209-256 (1977) 

Epstein, W. W., Poulter, C. D. A survey of some irregular monoterpenes and their biogenetic analogies to presqualene alcohol. Phytochemistry 12, 131-14 1 (1973) 

Nahrstedt, A. Strukturelle Beziehungen zwischen pflanzlichen und tierischen Sekundarstoffen. Planta Med. 44, 2-14 (1982) 

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A dicyclic monoterpene, the ( + )-form of which is found in oil of savin and many other essentia oils. The (—)- and racemic forms occur occasionally in nature. 

The product of this reaction is geranyl pyrophosphate Hydrolysis of the pyrophosphate ester group gives geramol a naturally occurring monoterpene found m rose oil... 

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 same tertiary carbocation serves as the precursor to numerous bicyclic monoterpenes A carbocation having a bicychc skeleton is formed by intramolecular attack of the rr electrons of the double bond on the positively charged carbon... 

This bicychc carbocation then undergoes many reactions typical of carbocation inter mediates to provide a variety of bicychc monoterpenes as outlined m Figure 26 7... 

The structure of the bicychc monoterpene borneol is shown in Figure 26 7 Isoborneol a stereoisomer of borneol can be prepared in the labora tory by a two step sequence In the first step borneol is oxidized to camphor by treatment with chromic acid In the second step camphor is reduced with sodium borohydride to a mixture of 85% isoborneol and 15% borneol On the basis of these transformations deduce structural formulas for isoborneol and camphor... 

Sabinene is a monoterpene found in the oil of citrus fruits and plants It has been synthe sized from 6 methyl 2 5 heptanedione by the sequence that follows Suggest reagents suitable for carrying out each of the indicated transformations... 

Terpenes, specifically monoterpenes, are naturally occurring monomers that are usually obtained as by-products of the paper and citms industries. Monoterpenes that are typically employed in hydrocarbon resins are shown in Figure 2. Optically active tf-limonene is obtained from various natural oils, particularly citms oils (81). a and P-pinenes are obtained from sulfate turpentine produced in the kraft (sulfate) pulping process. Southeastern U.S. sulfate turpentine contains approximately 60—70 wt % a-pinene and 20—25 wt % P-pinene (see Terpenoids). Dipentene, which is a complex mixture of if,/-Hmonene, a- and P-pheUandrene, a- and y-terpinene, and terpinolene, is also obtained from the processing of sulfate Hquor (82). 

Experimental procedures have been described in which the desired reactions have been carried out either by whole microbial cells or by enzymes (1—3). These involve carbohydrates (qv) (4,5) steroids (qv), sterols, and bile acids (6—11) nonsteroid cycHc compounds (12) ahcycHc and alkane hydroxylations (13—16) alkaloids (7,17,18) various pharmaceuticals (qv) (19—21), including antibiotics (19—24) and miscellaneous natural products (25—27). Reviews of the microbial oxidation of aUphatic and aromatic hydrocarbons (qv) (28), monoterpenes (29,30), pesticides (qv) (31,32), lignin (qv) (33,34), flavors and fragrances (35), and other organic molecules (8,12,36,37) have been pubflshed (see Enzyp applications, industrial Enzyt s in organic synthesis Elavors AND spices). 

Table 2. Properties of Selected Monoterpene Hydrocarbons and Ethers...

The sesquiterpenes found in essential oils have low volatilities compared with monoterpenes and so are isolated mainly by steam distillation or extraction, but some are also isolated by distillation or crystallization. Most of the sesquiterpene alcohols are heavy viscous Hquids and many crystallize when they are of high enough purity. Sesquiterpene alcohols are important in perfume bases for their odor value and their fixative properties as well. They are valuable as carriers of woody, balsamic, or heavy oriental perfume notes. 

One method of synthesis of taxol analogues starts with a-pinene (8), the readily available and inexpensive monoterpene derived from the processing of turpentine from the pine tree (200). The a-pinene is oxidized to verbenone, which is then alkylated and converted to taxol analogues in a multistep process. 

Another monoterpene used as a starting material for taxol analogues is camphor (43), which is readily available naturally or can be produced synthetically (201,202). Total synthesis of taxol analogues may be the answer toward finding new compounds for the treatment of many types of cancer. 

W. F. Erman, Studies in Organic Chemisty, Vol. 11, Chemistry of the Monoterpenes An Emyclopedic Handbook, Marcel Decker, New York, 1985. 

Wood is the raw material of the naval stores iadustry (77). Naval stores, so named because of their importance to the wooden ships of past centuries, consist of rosin (diterpene resin acids), turpentine (monoterpene hydrocarbons), and associated chemicals derived from pine (see Terpenoids). These were obtained by wounding the tree to yield pine gum, but the high labor costs have substantially reduced this production in the United States. Another source of rosin and turpentine is through extraction of old pine stumps, but this is a nonrenewable resource and this iadustry is in decline. The most important source of naval stores is spent sulfate pulpiag Hquors from kraft pulpiag of pine. In 1995, U.S. production of rosin from all sources was estimated at under 300,000 metric tons and of turpentine at 70,000 metric tons. Distillation of tall oil provides, in addition to rosin, nearly 128,000 metric tons of tall oil fatty acids annually (78). 

Elimination of water with the aid of sulfunc acid [9 14] and formation of the corresponding monoterpene hydrocarbons... 

In situ quantitation The fluorimetric analysis of monoterpene glucosides could be performed with advantage at 2exc = 313 nm and 2 > 390 nm. The detection limits of arbutin and L-menthylglucoside were 1 — 5 ng and 15 ng substance per chromatogram respectively (Fig. 1). 

Terpenes (Section 26.7) Compounds that can be analyzed as clusters of isoprene units. Terpenes with 10 carbons are classified as monoterpenes, those with 15 are sesquiterpenes, those with 20 are diterpenes, and those with 30 are triterpenes. 

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