Secondary Compounds Within the Anacardiaceae

ABSTRACT

        The Anacardiaceae includes 76 genera with over 600 species.  A survey of 
the literature, reveals that 25 of those genera contain poisonous species.  The 
principle function of secondary chemicals in this family is presumably as a 
defense against herbivores.  People worldwide are familiar with the compounds of 
the Anacardiaceae, more because of the rash they cause than their botanical 
interest.  Oleoresins of the Anacardieaceae cause cell-mediated contact 
dermatitis.  The proximal causes of this dermatitis and its treatment will be 
discussed.  Toxicodendron, the genus including poison-ivy is the most studied of 
the genera in this family, and an often neglected fact is the majority of the 
poisonous genera are tropical and poorly known.  Anacard compounds are of 
chemical interest and they hold great promise in the search for new medicinal 
and commercial agents.

INTRODUCTION

        Anacardiaceae are found around the globe and millions of people and 
animals are aquatinted with them, chiefly because of the irritant effects of 
their chemicals rather than their botanical interest.  The Anacardiaceae 
includes 76 genera with over 600 species.  There are four tribes of poisonous 
Anacardiaceae (Mitchell 1990).  The poisonous genera Anacardium, Gluta, 
Mangifera, and Switonia are members of the tribe Anacardeae.  Comocladia, 
Metopium, Toxicodendron, are in the tribe Rhoeae.  Semecarpus, Holigarna, and 
Melanochyla are in the tribe Semecarpeae.  Spondias is in the tribe Spondiadeae 
(Mitchell 1990).           The principle function of the secondary chemicals in 
the Anacardiaceae is probably to serve as a defense against vertebrate and 
insect herbivores.  Contact with the poisonous members of the Anacardiaceae 
usually causes a cell-mediated dermatitis. The nature of the peculiar medical 
reaction and its treatment will be discussed. 

        Virtually all of the Anacard oleoresins that induce contact dermatitis 
are mixtures of phenolics which vary primarily in the length, branching, number 
and position of double bonds in the hydrocarbon side chain, and in the number 
and position of hydroxyl groups on the benzene ring (Mitchell 1990).  The 
specific structures and properties of these chemical types will be discussed.  
Furthermore, while the negative properties of the plants in this family are most 
emphasized, the roles that the poisonous Anacardiaceae play in medicine and 
commerce are often positive.  Some Anacard compounds have a long history of use 
by humans and others are just now being discovered and developed.

THE NATURE OF RHUS DERMATITIS

        Poison-ivy is arguably the most notorious plant in the Anacardiaceae and 
because poison-ivy was placed in the genus Rhus when it first was described over 
200 years ago, the medical profession has labeled the dermatitis caused by 
poison-ivy and its relatives as "Rhus dermatitis".  This name is somewhat 
misleading given that most taxonomists now group only non-poisonous species in 
the genus Rhus ( poison-ivy, poison-oak, and poison-sumac are now in the genus 
Toxicodendron) (Gillis 1975).  

        Members of this notable plant family have a remarkable system of long 
ramifying canals in their branches, roots, leaves, and twigs.  These canals are 
known as laticiferous canals or resin canals (Venning 1948).  Because the toxic 
oleoresins are contained within these canals, brushing against an undamaged 
plant will not usually result in dermatitis.  However, undamaged plants are 
rare.  The Anacardiaceae are generally fragile and leaves can be adulterated 
quite easily by wind, animals, or chewing insects.  Damaged plants can be 
recognized by black splotches on the leaves which are caused by oxidation of 
oleoresins. 

        Oleoresins of the Anacardiaceae are generally mixtures of phenolic 
compounds which vary with respect to length, branching, degree of saturation, 
and side chain identity (Mitchell 1990).  Oleoresins are often called urushiols 
in scientific literature.  The human immune response to oleoresins is a cell-
mediated, delayed, hypersensitivity reaction (Baer  1983).  Dermatitis is 
induced when oleoresins act as haptens that bind to skin proteins covalently.  
The resulting protein-oleoresin complex is viewed by the body as foreign 
material and is thus attacked by the body's Thymus-dependent cells (Mitchell 
1990).  The skin erupts in blisters because its cells are being destroyed by the 
immune system.

        The symptoms of Anacardic poisoning can range from minor to severe.  
Ingestion of leaves and drupes (especially unripe ones) can cause 
gastroenteritis, hemorrhoids, headaches, and even death (Mitchell 1990).  
Asthma-like symptoms can be induced by unidentified volatiles from the flowers 
of Schinus terebenthifolius and Mangifera indica (Campbell 1983, Morton 1971).  
Photodermatitis is caused by Schinopsis quebracho-colorado (Lampe and Fagerstrom 
1968).  Photodermatitis is characterized by chemicals which cause cell damage 
when exposed to certain wavelengths of light.

        The allergic reaction to oleoresins usually begins within 24-72 hours of 
exposure, although some individuals experience symptoms as early as 6 hours 
after exposure.  Common symptoms of dermatitis due to Toxicodendron species are 
pruritis and erythema accompanied by edema.  Urticarial plaques and bullae may 
also develop (Epstein et al. 1997).  Rhus dermatitis can be almost immediately 
identified by the linear vesicles or papulovesicles that erupt on the skin (Behl 
and Captain 1979).  New skin lesions may appear on different parts of the body 
as long as two weeks after the initial eruption.  This phenomenon has led to the 
mistaken belief that the condition is spread by the blister fluid.  The outbreak 
occurs in stages either because some areas of the body are exposed to smaller 
urushiol concentrations or because there is a difference in the rate of 
absorbtion (Epstein et al. 1997).  For example, the thick skin on the feet will 
absorb urushiol at a slower rate than the delicate skin around the eyes. 

        Not all individuals are equally susceptible to dermatitis.  There is an 
age-associated difference in susceptibility.  Lejman et al. (1984) conducted an 
oleoresin patch test on two age cohorts (18-25 and 65-84).  In the older cohort, 
the allergic reaction developed more slowly and the inflammatory response was 
less than that observed in the younger cohort.  It is believed that immune 
system declines in function with age (Weksler 1981) and that the thymus-derived 
cells are particularly affected.  Immunodeficient deficient individuals such as 
those with leukemia or AIDS, may be less susceptible because contact dermatitis 
is a cell-mediated immune reaction (Epstein et al. 1997).  Individuals with 
asthma and/or allergies also seem to have a smaller incidence of contact 
dermatitis, perhaps because of diminished immune function or because they have a 
smaller predilection for outdoor activities and thus have less exposure to 
toxins (Epstein et al. 1997).

A CURE FOR RHUS DERMATITIS

        The bad news is that Rhus dermatitis has no cure.  The good news is that 
the condition is self-limiting and will usually resolve itself within two weeks 
of the initial outbreak.  Drugs can only ease suffering by treating the 
symptoms.  Relief can come from cold compresses or soaks with colloidal oatmeal.  
Oral antihistamines such as Benedryl often have a sedating effect and thus are 
comforting to patients who are too "itchy" to sleep.  Some clinicians believe 
that non-sedating antihistamines have no effect on the condition (Epstein et al. 
1997).  Patients using topical antihistamines such as diphenydramine HCl may 
experience alleviation of symptoms but they should be aware that sensitization 
from these drugs can occur.  Some doctors prescribe injected corticosteroids, 
but use of steroids is not warranted except in extreme cases or in cases in 
which the poison has been ingested or inhaled.  A topical fluorinated 
corticosteroid applied to the earliest red lesions can prevent a full-blown 
allergic reaction (Epstein et al. 1997).  However, most patients do not seek 
early treatment.

        No scientific research suggests that herbal treatments are effective.  
However, many individuals endorse applications of plantain, feverfew, and 
jewelweed (Epstein et al. 1997).  Prophylactics against poison-ivy are 
available.  The Food and Drug Administration approved the sale of Ivy Block, a 
lotion which forms a clay-like barrier against the plants' oily sap.  The active 
ingredient, quaternium-18 bentonite, is an organoclay with an excellent safety 
record (it has been used in cosmetic production for many years) (Epstein et al. 
1977).  Legend holds that American Indians used to chew poison-ivy leaves to 
confer immunity (Gillis 1975), but this practice is considered very dangerous 
and the myth has never been definitively proved.  Preparations for 
hyposensitization used to be commercially available, but their FDA approval was 
withdrawn due to overwhelming side-effects including pruritis and urticaria 
(Epstein et al. 1997).  Prophylactics based on cellular immunity are being 
explored but such drugs will not be available for quite some time.

CHEMISTRY OF ANACARDIC EXTRACTS

Brazilian Pink Pepper (Schinus terebinthifolius)

        The commercially available spice, pink pepper, is the one-seeded stone 
fruit of Schinus terebinthifolius RADDI.  Morton (1978) warned against their use 
by humans because they cause irritation of the digestive system, rashes, nausea, 
shivering, inflammations and allergies.  Lloyd et al. (1977) examined the 
essential oil from the stone fruit of S. terebinthifolius grown in Florida and 
found that it consists mainly of monoterpenes: alpha-pinene, beta-pinene, 
sabinene, delta3-carene, alpha-phellandrene, beta-phellandrene, limonene, beta-
cymene, and terpinolene.  Acute headaches and respiratory problems are believed 
to be caused by the mono-terpene volatiles from this fruit (Stahl et al. 1983).  
Pieribattesti et al. (1981) examined the fruit from S. terebinthifolius grown on 
Reunion and discovered compounds in different concentrations than those found in 
fruit from Florida.  Delta3-carene was found only in traces.  Also isolated were 
alpha-terpinene and  gamma-terpinene, not found in the plant from Florida.  The 
basis for the chemical differences has not yet been explored.  Based on 
chemotaxonomy, the thin-layer chromatogram, and reports of the seed's irritating 
effects, Stahl et al. (1983) expected to find phenolic substances in the seed 
extracts.  They examined the phenolic fraction of pink pepper and found cardanol 
15:1 to be present in a content of 0.03% in the fruit from Reunion and 0.05% in 
the fruit from  Florida.  A skin test of 10 mg cardanol 15:1 dissolved in 1 ml 
petroleum demonstrated the chemical's irritating nature.  Stahl et al. (1983) 
proposed that the toxic symptoms of pink pepper are due to cardanol 15:1 in 
combination with some other ingredients of the essential oil, especially delta3-
carene and phelandrene.  Their work is an excellent example of the important 
role of trace compounds in plant chemistry.

The Mango Tree (Mangifera indica)

        When the mango fruit is detached from its stem, a thin fluid 'Am ki 
Chep' exudes from it.  Mango "chep" is popularly regarded as a cure for scabies 
and other cutaneous infections.  Vasistha and Siddiqui (1937) suspected that the 
"chep" would have chemical constituents similar to those found in other plants 
of the Anacardiaceae.  From the dry mango "chep" a resin (mangiferen - C21H34O), 
a resinous acid (mangiferic acid - C40H60O4), and a resinol (Mangiferol - 
C21H36O2)5 were isolated and studied.  Contrary to expectations, these resinous 
principles were not found to be allied to bhilawanol or anacardic acid.  The 
degradation and oxidation products of mangiferen suggest that the chemicals are 
more related to the abietic acid series of resins, and support the view of 
resins being condensation products of isopren (Vasistha and Siddqui 1937).  More 
recent investigations of mango "chep" have led to the isolation of 
alkylgallates, amino acids, sugars, biflavones, and saponins (Khan and Khan 
1989, 1992, 1992).  Khan et al. (1994) discovered two new triterpenes in the 
roots of this species.  Their structures were determined as cycloartan-3B, 30-
diol and cycloartan-30-ol, respectively.

The Cashew Trees (Anacardium occidentale) (Semecarpus australiensis)

        A native of Brazil and the lower Amazon, the cashew has been introduced 
and is a valuable cash crop in the Americas, the West Indies, Madagascar, India, 
and Malaysia (Frankel 1991). Tyman and Morris (1967) described the composition 
of cashew nut shell liquid (CNSL) as anacardic acid (71.7%), cardol (18.7%), 
cardanol (4.7%), novel phenol (2.7%), and two unknown minor ingredients (2.2%).  
Each of the phenolic consituents was demonstrated by argenation-TLC to contain 
the saturated (trace only), monoene, diene, and triene cardanols.  Silver 
nitrate was used because, in its absence, the components of each phenol behave 
as a homogeneous material on Silica Gel G.  The existence of the novel phenol is 
of some significance biochemically and with regard to its possible role in the 
physiological action of CNSL.

        Murthy (1968)  describes the separation and identification of cardanol 
and cardol fractions of cashew nut shell liquid using paper, thin-layer, and 
column chromatographic methods.  Separation of cardanol according to the degree 
of unsaturation was achieved by chromatography on a silica gel-silver-nitrate 
column.  Cardanol, the main constituent of technical cardanol, was successfully 
separated into four components, viz. saturated, mono-, di-, and tri-olefins.  
The presence of a vinyl double bond in the tri-olefins was also confirmed.

        Native cashews (Semecarpus australiensis) are a well-known food source 
for aboriginal people of northeastern Queensland and the Northern Territory.  
Oelrichs et al. (1997) used solvent extraction and silica-gel chromatography to 
obtain a chemical fraction containing one major urushiol and minor components 
which corresponded to the di-trimethylsilyl derivatives of the poison ivy 
urushiol 3-n-pentadecylcatechol, its di and triene congeners, and to the poison 
oak urushiol mono and diene congeners of 3-n-heptadecyl catechol.  These 
compounds are similar to those found in the liquids from the nutshell of cashew 
(A. occidentale) (Oelrichs et al. (1997).

The Oriental Lacquer Tree (Toxicodendron vernicifluum formerly Rhus vernicifera)

        The oriental lacquer tree is cultivated for its sap which is used as a 
natural varnish.  Increasing exploitation of urushiols has caused a need for 
fast and accurate methods for the determination of the ratios of urushiol 
congeners in plant extracts.  Moreover, in order to examine the specificity of 
the immunological action in urushiol,  it is necessary to obtain each component 
in the underivatized form.  Urushiols can be difficult to isolate using regular 
gas-liquid chromatographic methods because the structural similarity of 
components causes their retention behaviors in GLC to be very similar. Isolation 
of the underivatized form is further complicated by the fact that the chemicals 
involved are highly sensitive to air oxidation.  Reverse phase LC has recently 
been found to be effective for separating urushiol congeners in the intact form.  
Du et al. (1984) describes an improved method for isolating intact urushiol 
congeners of Toxicodendron vernicifluum based on fused-silica capillary GLC.  
Owing to the inertness of the column wall, the problem of adsorption of urushiol 
on the column was completely eliminated. The authors demonstrated that all the 
constituents of urushiol that had been separated by RPLC were clearly 
distinguished using fused capillary GLC.  In addition, laccol and thitsiol 
derivatives, which are minor constituents in the sap, were discriminated.  This 
method holds promise for the analysis of other oily saps and extracts from 
plants in the Anacardeaceae.  Furthermore, Du et al. (1994) noted that the saps 
with good performance as a lacquer material had a high content of the trienyl 
compound compared with the monoenyl compound.  This observance may be explained 
by the fact that sap from lac trees dries through oxidative coupling of urushiol 
mediated by the oxidoreductase laccase.  The trienyl compound probably has a 
higher potential for this reaction than the monoenyl compound because its 
intermediate in the reaction (haptatrienyl cation) is more stable.

COMMERCIAL USES OF ANACARDIACEAE

        Cashew nut shell liquid, a byproduct of cashew nut processing, is also 
used in the manufacture of brake linings and electrical insulations (Mitchell 
and Mori 1987, Gillis 1975).  In fact, American servicemen stationed in the 
Canary Islands during the World War II erupted in poison-ivy like dermatitis 
after repairing airplanes.  The condition was cleverly traced to the fact that 
cashew nut shell lacquer had been used to coat the brake linings and electrical 
parts of the aircraft (Gillis 1975).

        Semecarpus anacardium shell liquid (oil) is used as an indelible ink to 
mark laundry (Behl & Captain, 1979; Burkill, 1935).  The fruits of S. anacardium 
are called dhobi-nuts after the name for Indian laundrymen, the dhobis.  One 
might think that this ink would be inferior to other because marks placed on the 
clothing can be transferred to the skin of the wearer.  To use another example 
of American servicemen, GIs stationed in India experienced dermatitis around 
their necks and waistlines, those places where a laundrymark had been placed in 
their uniforms (Gillis 1975).

        Anacardic acids, 2-methylcardols, and cardols isolated from various 
parts of the cashew (Anacardium occidentale) fruit have been found to exhibit 
tyrosinase inhibitory activity.  Kubo et al. (1994) completed studies with the 
two principle active compounds 6-[8(Z),11(Z),14-pentadecatrienyl salicylic acid 
and 5-[8(Z),11(Z),14-pentadecatienyl]resorcinol.  The results indicated that 
both of these phenolic compounds exhibit characteristic competitive inhibition 
of the oxidation of L-3,4-dihydroxyphenylalanine (L-DOPA).  Tyrosinase is one of 
the most important enzymes in the molting process and this research could 
results in the development of an alternative insect control agent.

POSSIBLE AND PROVEN MEDICINAL USES OF ANACARDIACEAE

        Toxicodendron species have been used in treatment of herpetic eruptions, 
palsy, paralysis, acute rheumatism and articular stiffness, and in various forms 
of chronic and abstinate eruptive diseases (Grieve 1971).  According to 
Blackwood (1959) and Clarke (1979) it is also used in typhoid fever, carbuncles 
in early stages, diarrhea, chronic dysentery, dyspepsia, effects fibrous 
tissues, joints, tendon, sheeth-aponeurosis etc.

        Rhus glabra is used as an astringent, antiseptic, in gargles, and as  
refrigerant and diuretic.  A strong decoction or diluted fluid extract, affords 
an agreeable gargle for angina and is useful in halting diarrhea.  In  
homeopathic system of medicine it is used in occipital headache, ulceration of 
mouth, stomatitis, epistaxic and profuse perspiration (Boericke 1984).

        Ethnobotanical studies of Rhus glabra revealed that native Indians used 
the plant in the treatment of bacterial diseases, such as syphilis, gonorrhea, 
dysentery, and gangrene (Erichson-Brown 1989).  The species was thus included in 
an antibiotic screening of British Colombian medicinal plants (McCutcheon et al. 
1992). The crude methanolic extracts of Rhus glabra were considered more 
effective than extracts of the other 100 plants screened.  The extract exhibited 
both the widest zones of inhibition in a disc assay, and the broadest spectrum 
of activity (active against all 11 species of bacteria tested).  Saxena et al. 
(1994) fractionated the chloroform/methanol extract and revealed three 
antimicrobial compounds which were purified.  These were gallic acid and two of 
its methylated derivatives, 3,4,5-trihydroxybenzoic acid and 4-methoxy-3,5-
dihydroxybenzoic acid.  Only gallic acid was isolated previously from this plant 
(Doorenbos 1976).  These compounds showed better activity against the gram-
negative bacteria (Escherichia coli and Pseudomonas aeruginosa) than the gram-
positive bacterium Staphylococcus aureus.  While this study explains the 
traditional uses of R. glabra by native peoples, it  is unlikely to lead to new 
antibacterial drugs.   The best activity observed for any compound isolated in 
this study gave an MIC of 12.5 µg/ml which is inferior to commercial antibiotics 
like polymyxin B, gentamycin,  or ceftazidime, all of which have MICs of 0.03-
1µg.ml against  Escherichia coli and Pseudomonas (Farmer et al. 1992).

        Ayurveda, the traditional science of health in India was used by Smit et 
al. (1995) to identify possible plant compounds for use in the fight against 
cancer.  Ayurveda is a philosophy that decrees that all matter is composed of 
wind, earth, water, fire, and wind - five basic elements which can be perceived 
by the five sense organs.  All food and drugs are classified according to their 
pharmacological properties, which are derived from these five elements.  Dried 
material of 14 species was submitted to ethanol (70% v/v) extraction and the 
extracts were tested for cytotoxicity on COLO 320 tumor cells, using the 
microculture tetrazolium (MTT) assay.  Extracts of the flowers of Calotropis 
procera (Ait.) R. Br. (Asclepiadaceae) and of the nuts of Semecarpus anacardium 
L.f. (Anacardiaceae) displayed the strongest cytotoxic effect with IC50-values 
of 1.4µg/ml and 1.6µg/ml, respectively.  The IC50-value is the concentration 
causing 50% growth inhibition of the tumor cells.  The extracts of several other 
plants did not show a cytotoxic effect up to 100µg/ml, the highest concentration 
tested.  Earlier studies of chloroform extract of S. anacardium nuts showed an 
activity of 150% T/C in a P388 test system in mice, at a dose of 50 mg/kg 
(Gothoskar et al. 1971).  Hembree et al. (1978)  found that a fraction of the 
aqueous methanolic extract of the nuts was active against Eagles 9KB nasopharynx 
carcinoma cell cultures, yielding an IC50-value of 2.3µg/ml.  This fraction 
consisted mainly of pentadecylcatechols.

        Ayurvedic Indian medicine including compounds from Semecarpus 
anacardium, Anacardium rohitaka, and Gluta glabra was tested by Prasad (1985) in 
a study of 250 cancer cases having different types and sites of malignancy.  The 
cases were divided into four different treatment groups (1) Ayurvedic drug and 
chemotherapy (2) Ayurvedic drug and radiation  (3) radiation (4) chemotherapy.  
The maximum response and longevity with minimum mortality was observed in those 
patients who were treated with the combined treatment of chemotherapy and 
Ayurvedic drug.   Notably, this combined therapy was most effective in leukemia 
and particularly those cases with spleenomegally and breast cancer.         The 
fungus Alternaria alternata (Fr.) Keilssler is responsible for the black spot 
disease of mango, Mangifera indica L., fruits in Israel.  Fungal development is 
thwarted or delayed by an antifungal activity in the peal of unripe mangos.  
This compound was characterized by H NMR, C NMR, and MS and identified as a 
mixture of 5-substituted resorcinols, whose major components are 5-(12-cis-
heptadecenyl)-resorcinol (65%) and 5-pentdecylresorcinol (15%) (Cajocaru et al. 
1986).

        An upsurge in the number of immunocompromised patients succumbing to 
fungal infections, has resulted in a demand for new antifungal compounds.  
McCutcheon et al. (1994) discovered that extracts of Rhus glabra branches 
exhibited antifungal activity.  The experiment was performed by placing extract 
impregnated paper discs on plates that were inoculated with fungal spores.  The 
diameter of the zones of  inhibition around each disc was used as a measure of 
antifungal activity. 

         Anticancer studies on Semecarpus anacardium reported have generally 
been generally carried out on the chloroform extract of the nuts.  Goudgaon et 
al. (1985) screened two major components of the chloroform extract, 
monoenepentadecyl catechol (bhilawanol-A) and dienepentadecyl catechol 
(bhilawanol-B) for anticancer activity.  When pure bhilawanol-A or pure 
bhilawanol-B was tested in vivo against the P-388 leukemia in mice, no 
significant anticancer activity was found for either of them.  The authors 
further hypothesized that the anticancer activity of nut extract could be caused 
by the presence of epoxides in the mixture resulting from autooxidation of the 
olefinic moiety of the bhilawanols.  Epoxy derivatives were synthesized and 
tested, but their anticancer activity was not significant.  

        Robustaflavone, a naturally occurring biflavanoid isolated from the seed 
kernel extract of Toxicodendron succedanea, was found to be a potent in vitro 
inhibitor of hepatitis B virus (HBV), with an effective concentration (EC50) of 
0.25µm and an in vitro selectivity index (IC50/EC90) of 153 (Linn et al. 1997).  
HBV is listed as the ninth leading cause of death by the World Health 
Organization.  The Food and Drug Administration has approved only one treatment 
from HBV (interferon-alpha) but the drug's response rate is not favorable.  
Further studies strongly suggest that robustaflavone acts via inhibition of the 
HVB polymerase.  This is significant because drugs currently in development are 
all nucleoside analogues, so robustaflavone may represent the only non-
nucleoside natural product inhibitor of HBV.  Thus, its potential for use in a 
combination regimen is very promising.

CONCLUSION

        The Anacardiaceae is an exceptional plant family.  Secondary chemicals 
found within the Anacards have a wide-spread influence on human life.  For 
example, the average American can probably locate, in his or her home, at least 
a few items derived from Anacardic compounds.  While much has been learned from 
the scientific research conducted to date, there is room for additional 
researchers in the field.  Only 12 of the 25 known or suspected genera have been 
chemically analyzed and only one to a few species of each genera have been 
studied (Mitchell 1990).  I predict the rise in number of ethnobotanists being 
trained, particularly in tropical areas,  will have an impact on the study of 
Anacardiaceae.  Furthermore, large biochemical prospecting companies will likely 
invest heavily in research of this plant family, which has produced so many 
promising leads for medical research.  Conspicuously absent from the literature 
is a connection between taxonomy and plant chemistry.  Perhaps this is because 
systematists are just now begining to use molecular data to elucidate the 
relationships between various members of the family.  Notably, the closest 
relative of the Anacardiaceae is the Burseraceae, a family that also has a 
reputation for its secondary compounds.  Comparison of plant chemistry and 
taxonomy may provide insight into the evolution of secondary compounds and 
phylogenies may be useful as "roadmaps" for chemical prospectors looking for 
related compounds. 

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