Terpenoids Lower.pdf

7/27/2019 Terpenoids Lower.pdf

1/7

Terpenoids: LowerJeffrey B Harborne, University of Reading, UK

Lower terpenoids are formed in plants either from acetyl-coenzyme A via mevalonate or

more directly from glucose via 1-deoxy- D-xylulose. Monoterpenoids are produced from

the condensation of two isoprene units, and sesquiterpenoids from three. Lowerterpenoids are secreted in glandular hairs on leaves or in the scent glands of flowers. They

provide many of the fragrant odours of plants. The best-known sesquiterpenoid is abscisic

acid, an important plant hormone involved in the opening and closure of leaf stomata.

Biosynthesis

All terpenoids are formed by head-to-tail condensation of5-carbon isoprene precursors, dimethylallyl diphosphate(DMAP) and isopentenyl diphosphate (IPP). Monoterpe-noids are formed from two such units (Figure 1) andsesquiterpenoids from three such units. These lower

terpenoids are relatively volatile compared to higherterpenoids, which require four or more isoprene units fortheir formation.

At one time, it appeared as though the two key C5intermediates, DMAP and IPP, were always formed viamevalonate from the condensation of three acetyl-coen-zyme A units, with subsequent loss of one carbon atom bydecarboxylation. More recent experiments have indicatedthe existence of an alternative route to DMAP and IPP

from glucose via the key intermediate 1-deoxy-d-xylulosand its 5-phosphate. This nonmevalonate pathway particularly associated with the leaf plastids but can occuelsewhere. Tracer feeding experiments have confirmed thaboth pathways to C5 intermediates operate in thbiosynthesis of the lower terpenoids (Lichtenthaler, 1999

In monoterpenoid biosynthesis, the first 10-carbointermediate, formed from the union of DMAP and IPPis geranyl diphosphate (Figure1). This may undergo furtheenzymatic modification to yield acyclic monoterpenes sucas geraniol itself, a principle in the oil of geranium, lemograss and rose, and linalool, from the oil of corianderHowever, many monoterpenoids are monocyclic (e.glimonene) or bicyclic (e.g. a-pinene) and therefore requira cyclizing enzyme to complete their biosynthesis.

Article Contents

Secondary article

. Biosynthesis

. Monoterpenes

. Iridoids

. Sesquiterpenoids

. Abscisic Acid as a Plant Growth Substance

. Sesquiterpene Lactones: Occurrence and Biological

Properties

HO

HO CH3

HO

OPP

OPP

Dimethylallyl diphosphate

Isopentenyl diphosphate

OH

CH3

OHO

HO

1-Deoxy-D-xylulose

Glucose3acetyl-coenzyme A

Mevalonate

OPPHO O

cyclase

Geranyldiphosphate

Limonene trans-Carveol Carvone

+

Figure 1 Biosynthesis of monoterpenoids formation of carvone in Mentha spicata.

ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group / www.els.net


2/7

Currently more than 20 monoterpenoid cyclases havebeen identified and are characterized in terms of the cyclicproduct formed. A series of enzymatic oxidations andreductions then come into operation to complete thesynthesis of the many different known monoterpenes. In atypical case, carvone, a major component of the oil of themint Mentha spicata, is formed from geranyl diphosphate

by a cyclase that converts it to limonene, and this isoxidized in a two-stage processvia trans-carveol to carvone(Figure 1).

A final step in the biosynthesis of monoterpenoids infruits may be the conjugation through a free hydroxylgroup (as in geraniol) with glucose to give a glucoside. Sucha glucoside may undergo catabolism during the ripeningprocess, with thereleaseof thefree monoterpene, as part ofthe attractive odour of that fruit.

The biosynthesis of iridoids or monoterpene lactonesfollows the same generalpathway as for monoterpenes, butseveral further enzymatic steps may be necessary. Thebiosynthesis of the iridoid aucubin in Plantago major is

illustrated in Figure 2. A key step is the oxidation of geranyldiphosphate to 10-hydroxygeraniol. This is subsequentlyfurther oxidized to the corresponding diketone, 10-oxogeranial, which first cyclizes to 8-epiiridodial and thenlactonizes to 8-epideoxyloganic acid. Several furthermodifications, together with the linking of a glucoseresidue, produce the final product, aucubin.

The biosynthesis of sesquiterpenoids begins with theformation of farnesyl diphosphate from the condensationof geranyl pyrophosphate and IPP. This then undergoes avariety of enzymatic modifications to produce the manysesquiterpenoids known in nature (Charlwood and

Banthorpe, 1991). Here, attention will be concentrateon the biosynthesis of abscisic acid, a sesquiterpene aciwith growth-regulating properties. Ever since its discoverin 1964, it has been assumed to be formed from farnesydiphosphate, according to the scheme shown in Figure 3However, an alternative pathway involving the degradation of a carotenoid, violaxanthin, and the intermediacy o

2-cis-xanthoxin has been proposed more recently. While is possible that both of these routes to abscisic acid operatin plants, the latest evidence from feeding and otheexperiments indicates that the degradative route via 2-cisxanthoxin is the favoured one (Parry, 1993).

OH

OH O

O

O

O

CO2H

O

OGlc

O

OGlcHO

HO

10-Hydroxygeraniol 10-Oxogeranial 8-Epiiridodial

8-Epideoxyloganic acid Aucubin

Geranyldiphosphate

Figure 2 Biosynthesis of iridoids formation of aucubin in Plantago major.

CHOO

HO

OPP CO2OH

O

Farnesyl diphosphate Abscisic acid

2-cis-Xanthoxin

Violaxanthin(C carotenoid)40

Figure 3 Alternative pathways of abscisic acid biosynthesis.

Terpenoids: Lower

2 ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group / www.els.net


3/7

Monoterpenes

Monoterpenes, together with sesquiterpenes and aro-matics, are components of plant essential oils. They tendto accumulate in members of certain families, such as theLabiatae, Pinaceae, Rutaceae and Umbelliferae, fromwhich theyare commerciallyproduced. They are employed

in flavouring food and in perfumery. Some monoterpenesare ubiquitous in their natural occurrence andcan be foundin small amounts in the volatile secretions of most plants.

Monoterpenes are particularly associated in the plantwith specialized secretory structures, such as oil cells,glandular hairs and resin ducts. Their main functions inplants are for attracting pollinators to flowers, and mostsweet-smelling floral scents are likely to contain a variety ofmonoterpene constituents. For example, limonene is adominant odour constituent of Citrus flower, whereasgeraniol is dominant in some rose petals. The role ofmonoterpenes as leaf constituents is less clear-cut, butthere is increasing evidence that leaves rich in monoterpe-

noid constituents are protected from herbivores. Forexample, camphor occurs in the leaves of white spruce,Picea glauca, and feeding experiments show that thiscompound repels snowshoe hares from browsing. Othermammals such as red deer avoid feeding on terpene-richleaves. Some Australian fauna, e.g. possums and koalabears, are able to eat eucalypt leaves containing limonene,cineole, piperitone and terpineol because they have becomespecially adapted. They avoid any deleterious nutritionaleffects by absorbing the terpenes from the stomach andsmall intestine and then detoxifying them via the liver(Harborne, 1993).

With over 700 known structures,monoterpenoids can be

classified into four arbitrary categories: acyclic, mono-cyclic, bicyclic and irregular. Typical acyclic monoterpenesare geraniol itself, biosynthetically the simplest (seeFigure 1), and then linalool, nerol and citronellol. The lastoccurs both free and in esterform in many plant oils, e.g. inBoronia citriodora (Rutaceae), and is especially prized bythe perfumery industry. Monocyclic terpenes includelimonene, a-terpineol and terpinolene, together with thetwo typical mint leaf oils, menthol and menthone.

Bicyclic monoterpenes, which are regularly present inplant essential oils, include a-pinene, b-pinene, borneoland thujone. a- and b-Pinene occur richly in the oleoresinof Pinus palustris and other Pinus spp., and are obtained

commercially from these bark oleoresins. Among irregularmonoterpenes are the tropolones of gymnosperm heart-woods, e.g. g-thujaplicin, while the pyrethrins of Tanace-tum cinerariifolium have extended use in agriculture fortheir insecticidal properties.

Much effort has been expended on the synthesis ofmonoterpenoids in plant cell culture and, after manyfrustrating failures, some successes have been achieved.For example, hairy root cultures of ginger, Zingiberofficinale, will produce geraniol and neral in reasonable

yield. Likewise, shoot organ cultures of Pelargoniumfragrans will forma-pinene, b-pinene and sabinene (Charwood et al., 1990). Also, the gymnosperm Pinus radiata icallus culture synthesizes a- and b-pinene at similar leveto those in the intact needles (Banthorpe et al., 1986).

Besides their widespread occurrence in plants, monoterpenoids are occasionallyfound in insects as pheromone

and as defence agents. Pine bark beetles use myrceneipsdienol and verbenone as aggregation pheromones. Thbeetles mayborrow the monoterpenes from the pines thefeed on, or alternatively synthezise them de novo. Againcompounds such as citral and citronellol are relativelnonspecific toxicants synthesized in the defensive secretions of ants or termites. Their odours may be sufficient tdeter an attacker, while the vapour may have an irritatineffect on the predators skin (Harborne, 1993).

Iridoids

The iridoids are a group of bitter-tasting monoterpenoilactones that have a restricted occurrence in dicotyledonous angiosperms. They are found in about 70 familiebelonging to some 13 orders (Jensen et al., 1975). Typicairidoid-containing plants are found in the LabiataPlantaginaceae, Scrophulariaceae and Valerianaceae. Iridoids are lactones, commonly with a glucose attachmento the hydroxyl of the lactone ring. A typical structure iloganin (Figure 4), which occurs in Strychnos nux-vomicfruit to the extent of 45% dry weight. Iridoid aglyconeafter hydrolysis of the sugar, are highly unstable anusually disintegrate.

A second group of iridoids have the five-membered rinof carboxylic iridoids opened, giving rise to seco-iridoidwhich have as a result an additional aldehyde function.Thseco-iridoid derived from loganin is seco-loganin (Figure4

OHO

H

HOGlc

CO Me2

CH3

HO

OGlc

CO Me2

HO2C

H2C

O

H

HOCH3

H

O

H

HOGlc

O

HOH2C

OH

Loganin Seco-loganin

cis-trans-Nepetalactone Catalpol

Figure 4 Structures of four iridoids.

Terpenoids: Lower



4/7

a widespread substance in the Caprifoliaceae. Seco-iridoids have another role in plant metabolism asbiosynthetic precursors of terpene alkaloids. Thus seco-loganin can condense with the amino acid tryptophan togive rise to the alkaloid corynantheine in Corynanthejohimbe (Rubiaceae).

A few volatile iridoids without glucose attachment are

present in plants, a notable example being nepetalactone(Figure 4), the active principle of catmint Nepeta cataria. Theplant has a peculiar attraction to members of the cat family.However, the purpose of its production in the plant is morelikely to be related to its insect-repellent properties.Structures similar to nepetalactone occur in the defensivesecretions of ants, stick insects andbeetles(Harborne, 1993).

Plants containing iridoids have been used in folkmedicine in the treatment of inflammation and as a bittertonic. Valepotriates, iridoids in Valeriana, are sedativeagents. Iridoids can be toxic and, in medieval times, breadcontaminated with iridoid-containing Rhinanthus seedcaused human deaths. Iridoids have been ingested from

food plants by various butterfly larvae and hence providethe adult with protection from bird predation. Forexample, catalpol from Plantago species is sequesteredand stored in this way by Euphydryas butterflies in NorthAmerica (Harborne and Tomas-Barberan, 1991).

Sesquiterpenoids

The sesquiterpenoids are chemically defined by theirformation from three isoprene units via the common C15precursor farnesyl diphosphate (see Figure 3). They co-

occur with monoterpenoids in plant essential oils and canusually be distinguished by their higher boiling points.There are three main groups, according to whether they areacyclic (e.g. farnesol), monocyclic (e.g. bisabolol) orbicyclic (e.g. b-cadinene) (Figure 5). Some are simpleunsaturatedhydrocarbons, but most have other functionalgroups as well. The derived sesquiterpenoid abscisic acid isa plant hormone and is discussed separately below.Sesquiterpenoids of one large group also have a lactonefunction, and these are also considered later.

The main occurrence of sesquiterpenes is in plantessential oils, and some structures such as bisabolol,caryophyllene and b-cadinene are widely present in leaf

oils of plants in the Labiatae, Rutaceae, Myrtaceae andPinaceae. Other compounds are of more restrictedoccurrence. Carotol, for example, is characteristic of thecarrot genus Daucus in the Umbelliferae. Another sesqui-terpenoid, rishitin, is confined to the Solanaceae, and hereit is only produced after a plant such as the potato isinfected by microorganisms (Bailey and Mansfield, 1982).

Besides occurring in higher plants, sesquiterpenes arewell represented in bryophytes (Asakawa, 1992) and inmicroorganisms. They are found additionally in marine

animals and are encountered in insect defence secretionSome insect pheromones are sesquiterpenoid in natureThis applies to (E)-b-farnesene, an alarm pheromone oaphids. It is also relevant here that one class of insechormone, juvenile hormone, is sesquiterpenoid in naturand such hormones (e.g. JH III) and hormone-mimics (e.gjuvabione) have been encountered in some quantity i

certain plants (Harborne, 1993).

Abscisic Acid as a Plant GrowthSubstance

Abscisic acid (ABA) was first discovered in 1964 as dormancy factor in plants. It accumulates, for example, idormant potato tubers and the dormant buds on trees. Ihas little to do with leaf abscission, as the name incorrectlhints, and it was only later that its regulatory role istomatal opening was established.

ABA is a sesquiterpene acid, with additional keto anhydroxyl functions. It occurs naturally as the opticallactive S-(1 )-form (Figure 3). The unnatural R-(2 )-ABAhas been synthesized but this has no effect whatsoever ostomatal opening. Two conjugates of ABA are regularlfound with it, the glucose ester and the 1 -glucoside. Therare several related metabolites known, including phaseiacid (Figure 6) formed from ABA during inactivation, anxanthoxin (Figure 3) which is a more potent growtinhibitor than ABA.

ABAis present universally in flowering plants.Howeveit is absent from liverworts, where its role may be taken bthe stilbenoid lunularic acid. All organs of higher plant

that have been analysed so far show the presence of thihormone, but the concentrations vary considerablyranging from about 10 mg kg21 in ripening fruit (e.gavocado, rose hip) to about 10mg kg2 1 in water plants.

The availability of mutant plants deficient in ABA haprovided new information on the effects of this key planhormone. Mutants of tomato plants lacking ABA loswater faster than they can replace it because their stomatcannot close. They are permanently wilted. When ABA supplied externally to these wilty mutants, their stomatclose and they become turgid (Neil and Horgan, 1985This, combined with many earlier results, confirms that thregulation of stomatal opening is the best-establishe

function for ABA.The involvement of ABA in the control of plan

dormancy is another established role. In the case of treeand shrubs, there is still some uncertainty, although thABA content of buds falls as the intensity of dormancdecreases in the spring. It is clear that ABA has a wedefined role in seed dormancy. Thus, seeds of maizmutants deficient in ABA germinate prematurely on thcob. They are known as viviparous mutants and normaseed maturation can only be restored by adding ABA

Terpenoids: Lower



5/7

Hence, ABA is essential for seed maturation, stimulatinthe accumulation of seed proteins during the dormanphase (Milborrow and Netting, 1991).

Current research in ABA is centred on its more generainvolvement in the adaptation of plants to abiotenvironmental stresses. There is evidence for reversiblprotein phosphorylation and for modification of cytosoli

calcium levels as intermediates in an ABA signal transduction cascade (Leung and Giraudat, 1998).

Sesquiterpene Lactones: Occurrenceand Biological Properties

Sesquiterpene lactones are chemically distinct from othesesquiterpenoids by the presence of a g-lactone system

CO2HOO

CO2GlcO

OH

Phaseic acid

ABA glucose ester

Figure 6 Structures of two abscisic acid metabolites.

CH2OH

Juvabione Rishitin

Farnesol

HCH3

HO

HO

HO

-Cadinene-Bisabolol

HCH3

HO

H

H

(E)--Farnesene

Carotol -Caryophyllene

HO

CH3

H

H

Figure 5 Structures of some plant sesquiterpenoids.

Terpenoids: Lower



6/7

Many have antitumour activity but their considerablecytotoxicity has so far prevented any useful anticancerapplications. They have a variety of other biologicalproperties, as will be described later.

These lactones are classified biogenetically, according tothe carbocyclic skeleton present, into four groups:germacranolides with a 10-membered ring, e.g. alatolide;

eudesmanolides with two fused six-membered rings, e.g.alantolactone; guaianolides with fused five- and seven-membered rings and a methyl at C4, e.g. artabsin; andpseudoguaianolides, as guaianolides but with a methyl atC5 (compare artabsin and ambrosin, Figure 7).

Besides thesefourmaintypes, thereare a variety of otherlactones, formed by further modification of the carbonskeleton during biosynthesis. Germacranolides are recog-nized as the most primitive type and other skeletal classescan be derived biogenetically from them (Seaman, 1982).Unfortunately, very little biosynthetic study has beendevoted to these lactones, so that we know very little aboutthe exact intermediates involved. Other structural mod-

ifications that can take place include hydroxylation,dimerization, glycosylation and the introduction ofchlorine or aromatic substituents.

At least 4000 lactones have been described and themajority of them have been obtained from a single plantfamily, the Compositae, where they are characteristic(Seaman, 1982). They have been reported occasionally inabout 16 other angiosperm families, the only other majorsource being the Umbelliferae. Additionally, they havebeen found once in the gymnosperms, in Cupressaceae,and from a few fungi and from liverworts.

In the Compositae, these lactones are found particularlyin aerial parts, leaves and flowering heads in concentra-

tions of about 5% dry weight. They are often located inleaf trichomes or in surface wax. Occasionally, theiroccurrence extends to the roots, as in chicory, Cichoriumintybus, where they are present in the latex. Complexmixtures are the rule rather than the exception andfrom 3 to 15 components may be found in a given planttissue.

The main roles assigned to sesquiterpene lactones todayis as defensive agents against herbivory and microbialinvasion. For example, 10-deoxylactucin and lactupicrin,the major lactones of chicory, Cichorium intybus, occur insufficient quantity to deter insect feeding and are bitterenough to protect the plant from mammalian browsing

(Rees and Harborne, 1985). In general, lactones exhibitsignificant antifeedant properties against locusts and armyworms and reduce the survival of insect larvae and adults.Certain lactones (e.g. geigerin) are toxic to livestock andothers (e.g. parthenin) are well known to cause allergiccontact dermatitis (as in Parthenium hysterophorus).Additionally, many sesquiterpene lactones have beenshown to have both antibacterial and antifungal activity.Parthenolide, which occurs in feverfew, Tanacetum parthe-nium, is recognized as the antifungal principle of this plant

(Blakeman and Atkinson, 1979). The same compoundincidentally, is responsible for the antimigraine propertieof feverfew, one of the few lactone-containing members othe Compositae useful in medicine.

OO

O

H

CH2

HOCH3H

CH3

Parthenin(pseudoguaianolide)

CH2OH O

CH2OH

H

CH3

O CH3

CH2

O

H

H

Alatolide(germacranolide)

CH3 O

O

H

HO CH3

CH3H

Artabsin(guaianolide)

CH2OH O

O

H

CH3O

CH2

8-Deoxylactucin(guaianolide)

CH3

OCH3

O

O

H H

Parthenolide(germacranolide)

H CH3H

O

O

CH3H

HHO HCH3

O

Geigerin(guaianolide)

O

O

H

H CH3

CH2

H

CH3O

Ambrosin(pseudoguaianolide)

O

H

O

CH2H CH3H

Alantolactone(eudesmanolide)

O

H

H

CH3H

H

H

H

H

CH3

Figure 7 Structure of representative sesquiterpene lactones.

Terpenoids: Lower



7/7

References

Asakawa Y (1992) Chemical constituents of the Hepaticae. Fortschritte

der Chemie Organischer Naturstaffe 42: 1286.

Bailey JA and Mansfield JW (eds) (1982) Phytoalexins. Glasgow:

Blackie.

Banthorpe DV, Brench SA, Njar VCO, Osborne MG and Watson DG

(1986) Ability of plant callus cultures to synthesise and accumulate

lower terpenoids. Phytochemistry 25: 629636.Blakeman JP and Atkinson P (1979) Antimicrobial properties and

possible role in hostpathogen interactions of parthenolide, a

sesquiterpene lactone isolated from the glands ofChrysanthemum

parthenium. Physiological Plant Pathology 15: 183192.

Charlwood BV and Banthorpe DV (eds) (1991) Methods in Plant

Biochemistry, vol. 7, Terpenoids. London: Academic Press.

Charlwood BV, Charlwood KA and Molina-Torres J (1990) Accumula-

tionof secondarycompounds by organisedplant cultures.Proceedings

of the Phytochemical Society of Europe 30: 167200.

Harborne JB (1993) Introduction to Ecological Biochemistry. London:

Academic Press.

Harborne JB and Tomas-Barberan FA (eds) (1991) Ecological

Chemistry and Biochemistry of Plant Terpenoids. Oxford: Clarendon

Press.

Jensen SR, Nielsen BJ and Dahlgren R (1975) Iridoid compounds, theiroccurrence and systematic importance in angiosperms. Botaniska

Notiser 128: 148180.

Leung J and Giraudat J (1998) ABA signal transduction.Annual Review

of Plant Physiology, Plant Molecular Biology 49: 199222.

Lichtenthaler HK (1999) The 1-deoxy-d-xylulose pathway of isoprenoid

biosynthesis in plants. Annual Review of Plant Physiology, Plant

Molecular Biology 50: 4766.

Milborrow BV and Netting AG (1991) Abscisic acid and derivatives. In:

Charlwood BV and Netting AG (eds) Methods in Plant Biochemistry,

vol 7, Terpenoids, pp. 213262. London: Academic Press.

Neil SJ and Horgan R (1985) ABA production and water relations in

wilty tomato mutants subjected to water deficiency. Journal of

Experimental Botany 36: 12221231.

Parry AD (1993) Abscisic acid metabolism. In: PJ Lee (ed.) Methods

Plant Biochemistry,vol9, Enzymes of Secondary Metabolism,pp.381

402. London: Academic Press.

Rees SB and Harborne JB (1985) The role of sesquiterpene lactones an

phenolics in the chemical defence ofthe chicory plant.Phytochemist

24: 22252231.

Seaman FC (1982) Sesquiterpene lactones as taxonomiccharacters in t

Asteraceae. The Botanical Review 48: 121595.

Further Reading

Charlwood BV and Banthorpe DV (eds) (1991) Methods in Pla

Biochemistry, vol. 7, Terpenoids. London: Academic Press.

Harborne JB (1993) Introduction to Ecological Biochemistry. Londo

Academic Press.

Harborne JB and Tomas-Barberan FA (eds) (1991) Ecologic

Chemistry and Biochemistry of Plant Terpenoids. Oxford: Clarendo

Press.

Jensen SR, Nielsen BJ and Dahlgren R (1975) Iridoid compounds, the

occurrence and systematic importance in angiosperms. Botanisk

Notiser 128: 148180.Leung J and Giraudat J (1998) ABA signal transduction.Annual Revie

of Plant Physiology, Plant Molecular Biology 49: 199222.

Lichtenthaler HK (1999) The 1-deoxy-d-xylulosepathway of isopreno

biosynthesis in plants. Annual Review of Plant Physiology, Plan

Molecular Biology 50: 4766.

Milborrow BV and Netting AG (1991) Abscisic acid and derivatives. I

Charlwood BV and Netting AG (eds) Methods in Plant Biochemistry

vol 7, Terpenoids, pp. 213262. London: Academic Press.

Parry AD (1993) Abscisic acid metabolism. In: PJ Lea (ed.) Methods

Plant Biochemistry,vol9, Enzymes of Secondary Metabolism,pp.381

402. London: Academic Press.

Seaman FC (1982) Sesquiterpene lactones as taxonomiccharacters in t

Asteraceae. The Botanical Review 48: 121595.

Terpenoids: Lower


Documents

Terpenoids Lower.pdf