Introduction

Phytochemicals, as the word implies, are the individual chemicals from which plants are made. In this chapter we will look at these materials, specifically the organic components of higher plants. Numerous journals, individual books, and encyclopedic series of books have been written on this subject. The goal here is to review this area in a concise form that is easily understandable and is written with the practicing natural-products chemist in mind. The reader not familar with chemistry may be somewhat intimidated by the material presented here, but we believe that understanding the chemical composition of plants is a prequisite to the remaining topics of this book. For those interested in reviewing a specific area in greater detail, the bibliography section provides numerous references for each organic group covered.

During the course of this survey, several themes will be emphasized. In order to demonstrate the rich diversity of structures which exist, numerous examples of each type of plant natural product will be provided. Often these will be derived from common plants with which most of us are familiar. Special attention will be paid to the herbal drugs, from which numerous natural products of all types can be found. Finally, some mention will be made of marine plants, from which many truly unique individual bioactive components have been isolated.

The general categories of plant natural products are organized very broadly in terms of increasing oxidation state. This begins with the lipids, including the simple and functionalized hydrocarbons, as well as the terpenes, which are treated separately. Following this are the unsaturated natural products, including the polyacetylene and aromatic compounds. We then cross over into the realm of the primarily hydrophilic molecules including the sugars, and continue with those which can form salts, including the alkaloids, the amino acids, and the nucleosides. Overall, this scheme provides a simple organizational pattern for the phytochemicals. It is consistent with the way chemists often categorize organic chemicals in general, and roughly is equivalent to a normal-phase chromatographic analysis of a given plant species. Like any organizational scheme for this subject, be it taxonomic, phylogenetic, or biochemical, it should serve only as a rough guide.

1.2 LIPIDS

Lipids are water-insoluble biomolecules that are soluble in nonpolar solvents. This very broad definition allows for the inclusion of a variety of structural types, all of which contain a large hydrocarbon region in their structure. Biologically, lipids provide (1) the main structural components of membranes, (2) sources of fuel for storage and transport, and (3) protective surface coatings. The lipid-based cell surface components also may be involved in cell recognition, species specificity, and tissue immunity.

1.2.1 Hydrocarbons

Comprising a relatively small group of compounds, the least polar organic natural products are the hydrocarbons. These aliphatic hydrocarbons usually have an odd number of carbon atoms, resulting from the decarboxylation of their fatty acid counterparts. Several representative structures are shown in Figure 1.1. Devoid of any heteroatoms, these compounds have relatively simple structures. Hydrocarbons may be either saturated or unsaturated — the latter contain multiple bonds. Each double bond results in two less hydrogen atoms relative to the saturated counterpart, and is thus in a higher oxidation state. Note that those highly branched hydrocarbons derived from isoprene can exist as hydrocarbons; however, these materials (terpenes) will be considered separately in Section 1.2.3.

FIGURE 1.1 Hydrocarbon natural products.

1.2.1.1 Saturated Hydrocarbons

Saturated hydrocarbons are the simplest and least polar organic natural products. Common examples such as hexane CH3(CH2)4CH3 are not generally found in plants, but rather are derived from fossilized plant and animal matter. Turpentines, commonly used as paint removers, consist of simple hydrocarbons, particularly n-heptane, as found in conifers, including Pinus jeffreyi and P. sabiniana. In living plants, saturated hydrocarbons are universally distributed as the waxy coatings on leaves, and as cuticle waxes on the surfaces of fruits. Typical examples include n-nonacosane and hentriacontane (Figure 1.1). Several plants are rich in aliphatic hydrocarbons used in vegetable oils. For example, olive oil contains hydrocarbons ranging from C13 to C28. Branched simple alkanes (again excluding terpenes) rarely occur in significant quantity in plants.

1.2.1.2 Unsaturated Hydrocarbons

The simplest unsaturated hydrocarbon is ethlyene, an important plant hormone. Larger unsaturated hydrocarbons are also common as plant waxes. Exceptionally high amounts of alkenes have been detected in rye pollen, rose petals, and sugar cane. As the chain length and degree of unsaturation increases, the hydrocarbons become waxy and then solid at room temperature. Waxes may be either long chain hydrocarbons or esters of fatty acids.

1.2.1.2.1 Polyacetylenes

Unsaturated natural products can, of course, not only contain double bonds, but triple bonds, either in the form of acetylenes or nitriles. The polyacetylenes are a unique group of naturally occurring hydrocarbon derivatives characterized by one or more acetylenic groups in their structures. The sp hybridization of the triple bond results in a linear shape for this region of the molecule. A listing of some typical polyacetylenes (Figure 1.2) shows that these molecules often contain a wide variety of additional functional groups. The domestic carrot, for example, contains four polyacetylenes, the major one being falcar-inol, which is a mild neurotoxin found only to be present in 2 mgkg-1 (dry weight) of carrot roots. Other plants such as the water dropwort, Oenanthe crocata, are commonly found near streams in the Northern Hemisphere and contain several toxic polyacetylenes and should not be consumed.

Polyacetylenes have been found to have a fairly specific distribution in plant families, existing regularly only in the Campanulacae, Asteraceae, Araliaceae, Pittosporacae, and Apiaceae. Polyacetylenes are also found in the higher fungi, where their typical chain length is from C8 to C14, whereas the polyacetylenes from higher plants are typically from 14 to 18 carbons in length.

Biosynthetically, the polyacetylenes are likely to be derived by enzymatic dehydrogenation from the corresponding olefins. The toxicity of many of the polyacetylenes including those in the aforementioned water dropwort (Oenan-the crocata) as well as fools parsley (Aethusa cynapium) may form the basis for their role in some plants. Similarly, both wyerone acid in the broad bean (Vicia faba) and safynol in safflower oil from Carthamus tinctorius have been

KunclËvilluid lljdnK-.u-krfwii.

FIGURE 1.2 Some common functionalized hydrocarbon plant natural products, including polyacetylenes.

shown to act as natural phytoalexins, helping to deter the microorganisms which attack these plants.

1.2.2 Functionalized Hydrocarbons

Excluding the lipids and the terpenes, simple functionalized hydrocarbons are less abundant but not uncommon in plants. Here, we consider these in ascending order from halide to alcohol and sulfur-containing hydrocarbons, then to aldehydes and ketones, stopping just before the hydrocarbon acids (lipids). Some typical functionalized hydrocarbons and polyacetylenes are shown in Figure 1.2.

1.2.2.1 Halogenated Hydrocarbons

Although virtually unknown among terrestrial plant natural products, the marine environment has long been recognized as a source for hydrocarbons that contain both chlorine and bromine. Hundreds of different halogenated natural products have been isolated, particularly from the red algae and the animals that feed upon them. Various species of red algae from the genus Laurencia, for example, have been found to contain numerous halogenated natural products, including laurinterol, spirolaurenone, and laurencin (Figure 1.3)

Hallifl.i-ni.-ltil PliUl ^iiliu-ml PrcJivlT

l.juriDh.'ii.-il ipir.Uiur^conL

FIGURE 1.3 Halogenated plant natural products.

1.2.2.2 Alcohols

A large variety of volatile alcohols, e.g., aldehydes, ketones, and esters, occur in small concentrations in plants and have been classically referred to as essential oils. Their role may be related to their often strong odors, attracting them to insect pollinators and animal seed disseminators (see Chapter 2). All of the straight-chain alcohols from Q (wood alcohol) to C10 have been found in plants in either free or esterified form. Several, including ceryl alcohol, CH3(CH2)24CH2OH, a regular constituent of cuticular waxes, are shown in Figure 1.2.

1.2.2.3 Sulfides

Hydrocarbon sulfides are found in relatively few plants. Those that contain them, such as skunk cabbage, are readily recognizable by their obnoxious odors. Sulfides, including the simple hydrocarbon sulfides, are common in the species of Allium, many of which are lachrymators (substances which make eyes water) and have pungent odors. Thiophenes are limited primarily to the Asteraceae family, and are found in association with the polyacetylenes. The glucosinolates or mustard oil glucosides are also readily detected and help to create the flavors of the mustard, radish, onions, and garlic. Finally, perhaps the most common sulfur containing natural products are the amino acids cysteine and methionine.

l.ïuiciuiri l.ïuiciuiri

1.2.2.4 Aldehydes and Ketones

Simple aldehyde and ketone plant natural products are uncommon. Rare examples include hentriacontan-14-16-dione (C31H60O2), a major wax constituent of cereals and other grasses.

1.2.2.5 Esters

Esters are the condensation products of alcohols and acids. They tend to have strong and often pleasant odors. A listing of volatile ester constituents of various fruits is shown in Table 1.1.

TABLE 1.1

Volatile Ester Components of Strawberries, Apples, and Pineapples

Strawberries

Ethyl butyrate Ethyl isovalerate Isoamyl acetate Ethyl caproate

2-Hexenyl acetate

Apples

Ethyl acetate Ethyl butyrate Ethyl valerate Propyl butyrate

Pineapples

Ethyl acetate Methyl isocaproate Methyl isovalerate Methyl caprylate

Ethyl acrylate

1.2.2.6 Fatty Acids

Fatty acids are the simplest lipids. They are compounds that are usually characterized by a polar hydrophilic head region connected to a long hydrophobic hydrocarbon tail. Some lipids, including the fats, are used for energy storage but most are used to form lipid constituents of membranes, i.e., membranes that surround cellular organelles as well as protoplasts (the plasma membrane).

There are well over a hundred different types of fatty acids, though the most common in plants are oleic and palmitic acid. The hydrocarbon chain may be saturated, as in palmitic acid, or unsaturated, as in oleic acid. Fatty acids differ from each other primarily in chain length and the locations of multiple bonds. Thus, palmitic acid (16 carbons, saturated) is symbolized 16:0 and oleic acid, which has 18 carbons with one cis double bond at carbon 9 is symbolized 18:1A9. Double bonds are assumed to be cis unless otherwise indicated. Several common fatty acids are shown in Figure 1.4.

Although fatty acids are utilized as building-block components of the sapon-ifiable lipids, only traces occur in the free-acid form in cells and tissues. Normally these exist in various bound forms and may comprise up to 7% of the weight of dried leaves. They include long chain esters (waxes), triacylglycerols (fats),

l'*tt> Arid»

Slniclun

[ ¿LUTIL

rn-jrn^^iXH

C.Hr(CH:Jl:i:(XH

1 'jJimOf

t:nl(c;]j:j14lt:<)kH

5ll-.U M.'

CH^fllO, ..CO-H

Ar.khiJK1

Ri^nk'

CHjlCli^^.CCKH

rn,if:E[:iii-N=ri lifiioJTCMi

1 Jikiln.'

f Ht ! CH ; 1 jf " H =CHOU"H -CHC ïi:0 1 -CHiC \U) ¡i O-h [

.■'iniihiLkTiiL

f!]än!("!F[;1 ^ rn(CMo, t

FIGURE 1.4 Some common fatty acids.

as well as glycerophospholipids and sphingolipids (membrane lipids) (Figure

FIGURE 1.5 Some common fatty acid esters (lipids). 1.5).

Some generalizations can be made concerning the various fatty acids of higher plants. The most abundant have an even number of carbons ranging from C14 to C22. Unsaturated fatty acids predominate in higher plants, with oleic

FIGURE 1.5 Some common fatty acid esters (lipids). 1.5).

Some generalizations can be made concerning the various fatty acids of higher plants. The most abundant have an even number of carbons ranging from C14 to C22. Unsaturated fatty acids predominate in higher plants, with oleic acid (C18) being one of the most common. Unsaturated fatty acids have lower melting points than saturated fatty acids of the same chain length.

Waxes containing polymeric esters formed by the linking of several ra-hydroxyacids are especially prominent in the waxy coatings of conifer needles. The two most common acids in such waxes are sabinic [HOCH2(CH2)10CO2H] and juniperic acid [HOCH2(CH2)14CO2H]. The lipid constituents of cork and cuticle are known as suberin and cutin, respectively, and are composed of high molecular weight fatty acid esters.

1.2.3 Terpenes

The terpenes are among the most widespread and chemically diverse groups of natural products. Fortunately, despite their structural diversity, they have a simple unifying feature by which they are defined and by which they may be easily classified. Terpenes are a unique group of hydrocarbon-based natural products whose structure may be derived from isoprene, giving rise to structures which may be divided into isopentane (2-methylbutane) units (Figure 1.6).

I1 rncLh\ L- 1.1. hcLilifnfI (2-meill} IbutitfO

FIGURE 1.6 The terpenes are comprised of isoprene units.

Terpenes are thus classified by the number of 5-carbon units they contain:

Hemiterpenes

C5

Monoterpene

C10

Sesquiterpene

C15

Diterpene

C20

Sesterterpene

C25 (very rare)

Triterpene

C30

Tetraterpenes

C40

Like all natural products, within this simple classification lies an enormous amount of structural diversity which leads to a wide variety of terpene-like (or terpenoid) compounds. Note that the simplest examples of the terpenes are technically hydrocarbons, though they are considered separately here because of their common structural features. Not surprisingly, the terpenes are of a similar biogenetic origin, in which isopentenyl pyrophosphate and dimethylallyl pyrophosphate combine to yield geranyl pyrophosphate, leading to monoterpe-nes. Similarly, compounds derived from farnesyl pyrophosphate lead to sesquit-erpenes, and triterpenes are formed from two equivalents of farnesyl pyrophos-

phate. These various combinations and oxidations give rise to a large variety of terpenes, which will be surveyed briefly here.

The function of terpenes in plants (see Chapter 2) is generally considered to be both ecological and physiological. Many of them inhibit the growth of competing plants (allelopathy). Some are known to be insecticidal; others are found to attract insect pollinators. The plant hormone, abscissic acid, is one of the sesquiterpenes. One, gibberellic acid, is another one of the major plant hormones (over 90 gibberellins have been identified). The variety of structures that the terpenes possess is vast.

1.2.3.1 Hemiterpenes: C5

Isoprene itself does not occur free in nature but several five-carbon compounds are known which contain the isopentane skeleton, including isoamyl alcohol, isovaleraldehyde, tiglic acid, angelic acid, and P-furoic acid. Several common plant hemiterpenes are shown in Figure 1.7.

FIGURE 1.7 Some common plant hemiterpenes.

FIGURE 1.7 Some common plant hemiterpenes.

1.2.3.2 Monoterpenes: C10

Nearly all possible decane arrangements appear to exist in nature. This gives the term terpenoid a particularly elastic meaning and is remiscent of some of the current combinatorial efforts employed in the pharmaceutical industry. The monoterpenoids are the major component of many essential oils and, as such, have economic importance as flavors and perfumes. Common aliphatic examples include myrcene, geraniol, and linalool. Open chain structures include many well-known compounds, including menthol, camphor, pinene, and limonene. A variety of common monoterpenes are shown in Figure 1.8.

Most of the monoterpenes listed in Figure 1.8 come from common sources with which most of us are familiar. Myrcene is found in the essential oil of bay leaves as well as hops. It is used as an intermediate in the manufacture of perfumes. Geraniol, which is isomeric with linalool, constitutes the major part of the oil of roses and is also found in essential oils of citronella, lemon grass, and others. Menthol is a well-known monoterpene which is found in the essential

Zeichen Symbole Bedeutung
FIGURE 1.8 Some common plant monoterpenes.

oil of peppermint and other members of the mint family. Carvone is a common monoterpene which is one of the main odoriferous components of caraway seed (Carum carvi). Linalool is one of the principle constituents of coriander (Cori-andrum sativum), a common spice. Safranal is chiefly responsible for the characteristic odor of saffron (Crocus sativus). Eucalyptol, also known as cineole, is the main component of the essential oil of eucalyptus leaf (Eucalyptus spp.). Eucalyptol, along with camphor, form the major constituents of rosemary oil. Mullein, a common tomentose biennial, produces a number of iridoid glycosides, including aucubin.

1.2.3.3 Sesquiterpenes: C15

Derived from three isoprene units, the C15 sesquiterpenes exist in a wide variety of forms, including linear, bicyclic, and tricyclic frameworks. Like the monoter-penes, most of the sesquiterpenes are considered to be essential oils because they belong to the steam distillable fraction often containing the characteristic odoriferous components of the plant. An important member of this series is farnesol whose pyrophosphate serves as a key intermediate in terpenoid biosynthesis (see

KfUUUfUWl

FIGURE 1.9 Some common plant sesquiterpenes.

FIGURE 1.9 Some common plant sesquiterpenes.

Chapter 2). Some common sesquiterpenes are shown in Figure 1.9.

The cadinenes occur as essential oils from juniper and cedar trees and santonin is an antihelmintic that is isolated from wormwood (Artemisia maritima). Caryophyllene, first synthesized in 1964, is one of the principal components of oil of cloves. Helenalin is one of numerous pseudoguaianolide sesquiterpene lactones isolated from arnica oil (Arnica montana). Psilostaychin, an eudes-mane-type sesquiterpene lactone, is one of over 100 identified constituents of mugwort (Artemisia vulgaris). Acorone is a sesquiterpene diketone present in the essential oil of sweet flag (Acorus calamus). The sesquiterpene a-cadinene is one of the more than 70 isolated components from the essential oil of juniper berries. It has been used as a diuretic and antiseptic. Finally, tetrahydroridentin B is one of the bitter eudesmolides unique to the common dandelion (Taraxacum officinale).

1.2.3.4 Diterpenes: C20

The diterpenes are a widely varied group of compounds based on four isoprene groups, most of which are of limited distribution in the plant kingdom. Because of their higher boiling points, they are not considered to be essential oils. Instead, they are classically considered to be resins, the material that remains after steam distillation of a plant extract. The diterpenes exist in a variety of structural types (a selection is shown in Figure 1.10).

FIGURE 1.10 Some common plant diterpenes.

Many interesting examples may be mentioned. The cyclic ether zoapatonol is derived from the Mexican plant Montanoa tomentosa and has been used as an abortifacient. A number of clerodanes have been isolated from the Ajuga, Salvia, and Teucrium species, and have been found to possess insecticidal activity. A variety of cytotoxic lactones have been isolated from Podocarpus species. These podolactones have plant regulatory properties as well as antileukemic activity. The gibberellins comprise an important group of plant hormones. These fall into two series, including a C20 family represented by gibberellin A13 and a C19 series for which gibberellic acid is typical. Marrubin is a diterpene lactone from white horehound (Marrubium vulgare), which has been used as a bitter and choleretic in digestive and biliary complaints. Taxol, discovered by Wani et al. (1971) is a wholly unique antimitotic agent which binds to microtubules and stabilizes them as opposed to all other antimitotics of the tubulin-binding type, such as vincristine, the podophyllotoxins, and colchicine.

1.2.3.5 Triterpenes: C30

The C30 terpenes are based on six isoprene units and are biosynthetically derived from squalene. They are often high-melting colorless solids and are widely distributed among plant resin, cork, and cutin. There are several important groups of triterpenes, including common triterpenes, steroids, saponins, stero-lins, and cardiac glycosides. Among these is azadirachtin, a powerful insect antifeedant, first isolated in 1985 from Neem oil. Several triterpenes are shown in Figure 1.11.

1.2.3.5.1 Common Triterpenes

Only a few of the common triterpenes are actually widely distributed among plants. These include the amyrins and ursolic and oleanic acid which are common on the waxy coatings on leaves and as a protective coating on some fruits. Other triterpenes include the limonins and the cucurbitacins.

1.2.3.5.2 Sterols

The general steroid structure is shown in Figure 1.12. Practically all plant steroids are hydroxylated at C-3 and are in fact sterols. In the animal kingdom, the steroids have profound importance as hormones, coenzymes, and provitamins. However, the role of the phytosterols is less well understood.

1.2.3.5.3 Saponins

Saponins are high-molecular-weight triterpene glycosides containing a sugar group attached to either a sterol or other triterpene. They are widely distributed in the plant kingdom and composed of two parts: glycone (sugar) and aglycone or genin (triterpene). Typically, they have detergent properties, readily form foams in water, have a bitter taste, and are piscicidal (toxic to fish). Many of the plants that contain saponins have been used historically as soaps. These include soaproot (Chlorogalum pomeridianum), soapbark (Quillaja saponaria), soapberry (Sapindus saponaria) and soapnut (Sapindus mukurossi).

FIGURE 1.11 Some common plant triterpene natural products.

Saponins are constituents of many plant drugs and folk medicines, especially among Asian peoples. This has led to great interest in the investigation of their pharmacological properties. By 1987 over 1000 sapogenins and triterpene gly-cosides had been elucidated.

The aglycones, or genins as they are sometimes called, may be of the triter-pene, steroid, or steroid alkaloid class. Saponins may be mono- or polydesmodic, depending on the number of attached sugar moieties (Figure 1.13). The most common monosaccharide groups and their corresponding abbreviations are shown in Table 1.2.

Biosynthetically, the saponins are comprised of six isoprene units and are derived from squalene. Many details, including the cyclase enzymes involved, have recently been determined. Commercially important preparations based on saponins include sarsaparilla root (Sarsaparilla spp.), licorice (Glycyrrhiza spp.), ivy leaves (Hedera spp.), primula root (Primula spp.), as well as Ginseng (Panax spp.). The structures of the ginsenosides and glycyrrhizinic acid are shown in Figure 1.14.

FIGURE 1.12 Some plant sterol natural products.
FIGURE 1.13 Classification of saponins.

The ammonium and calcium salts of glycyrrhizinc acid are referred to as the glycyrrhizins. At 50 to 100 times sweeter than sucrose, these are the active

TABLE 1.2 Common Saponin Monosaccharide Groups

D-Glucose Glc

D-Galactose Gal

D-Glucuronic acid GlcA

D-Galacturonic acid Gal

L-Rhamnose Rha

L-Arabinose Ara

D-Xylose Xyl

D-Fucose Fuc

FIGURE 1.14 Naturally occurring saponins.

ingredients in licorice root (Glycyrrhiza glabra), with expectorant, bacteriostatic, and antiviral activity. The ginsenosides are one of many triterpene saponins from ginseng (Panax ginseng) believed to be responsible for its immunostimulant activity.

1.2.3.6 Tetraterpenes: C40

The most common tetraterpenoids are the carotenoids, a widely distributed group of C40 compounds. Whereas the structures of the di- and triterpenes can have a wide variety of fascinating structures, the carotenoids are generally derived from lycopene. Cyclization at one end gives y-carotene and at both ends provides P-carotene. This pigment, first isolated in 1831, is by far the most common of all of these pigments and virutally universal in the leaves of higher plants. As is evident from this polyene structure, numerous doublebond isomers are possible for these basic structures, all of which can provide brightly colored pigments. Thus, in plants, carotenoids serve both as necessary pigments in photosynthesis and as coloring agents in flowers and fruits. This normally results in colors varying from yellow to red. They are also believed to protect plants from overoxidation catalyzed by other light absorbing pig ments such as the chlorophylls. Some selected tetraterpenes are shown in Figure 1.15.

FIGURE 1.15 Representative plant tetraterpenes.

Was this article helpful?

0 0
Healthy Chemistry For Optimal Health

Healthy Chemistry For Optimal Health

Thousands Have Used Chemicals To Improve Their Medical Condition. This Book Is one Of The Most Valuable Resources In The World When It Comes To Chemicals. Not All Chemicals Are Harmful For Your Body – Find Out Those That Helps To Maintain Your Health.

Get My Free Ebook


Post a comment