William R. Roderick
University of Florida Gainesville
I I
9r"dural h k t y
Organic chemistry began with investigations in the chemistry of natural products, and for quite some time there was an emphasis on natural products. As the chemistry of synthetic organic compounds developed, there gradually arose a division between natural and synthetic chemistry. Certain classes of compounds were produced both naturally and synthetically, but those produced only synthetically continued to increase. That is, naturally occui~ing compounds, though quite numerous, seemed to fall into a relatively small number of classes of stable compounds; reactive, unstable compounds could be produced in the laboratory, but they apparently did not occur naturally. Thus the variety of structures produced in nature seemed to be limited. These observations led to a philosophy that only certain functional groups could exist in naturally occurring compounds, an argument occasionally employed to eliminate certain structures as possibilities for natural products. The classic example concerns the isolation in 1889 of a naturally occurring acetylene followed by a 50 year lag in the chemistry of natural alkynes, which has been attributed to the assignment of an incorrect structure to this compound by a worker who was "obviously prejudiced against the occurrence of acetylenic compounds in nature" ( 1 ) . Again, in 1930 it was assumed that a formula C.H2,2 could be accounted for only by double bonds or rings, "acetylenic linkages being unknown in nature," ($), although an alkyne had been correctly characterized in 1902 (5). Among natural product chemists this philosophy occasionally is still found, although mainly in the form of a restraint: "The oxiran group occurs in natural products so exceedingly rarely [about 20 examples were known a t the time] that its proposal merits exceptional concern" (4, 1956) and "the contention expressed by many biologists, upon purely theoretical grounds, that the compounds (which contain terminal methylene linkages) wonld be too reactive to exist in biological systems had to be disproved" (5, 1952). Judging from the persistence of such attitudes among the specialists, it seems qnite certain that chemists in general are probably not aware of the apparently infinite variety of structures which are now known to occur naturally. Furthermore, most textbooks impart a distorted impression of what types of organic compounds occur naturally and what types do not occur naturally. It is the purpose of this review to provide chemists, particularly the teachers of organic chemistry but also the nonorganic chemists, with an appreciation for the variety of chemical structures that occur naturally. In view of the very large number of natural products, the plan adopted has been the selection of 2 / Journol
of Chemical Education
0f
Natural Products
examples from the various classes rather than an inclusive coverage. Where review articles on the entire class are available, references are given to them rather than to the individual papers dealing with the examples presented. A Recent Expansion
The most obvious characteristic of the broadening horizons of the structural chemistry of natural products is its recentness. Indeed, almost every review article on the newer classes of natural products begins with a statement such as, "During the past ten years, more than . . . new members of this class of compound have been isolated, whereas prior to 1950 only a few (or none) were known." This recent expansion reflects, of course, the general expansion of chemistry during the past ten years. One of the factors has been the development of new techniques for the isolation and purification of compounds, such as ion-exchange and the various types of chromatography, and of new techniques for the identification and structural characterization of compounds, such as infrared and nuclear magnetic resonance spectroscopy. The numerous reasons why these techniques are of particular benefit to t.he natural product chemist should be obvious. Second, once the structure of a new type of compound has been elucidated, the isolation and characterization of similar compounds from the same or related species are considerably easier, and other examples usually follow. This is well illustrated in the studies of alkynes and free amino acids found in plants. Third, chemists are devoting more time to investigations of microorganisms, rather than to the relatively well studied plants. Indeed, many of the structures previously thought to he too unstable to occur naturally have been obtained from microorganisms, and it would appear that the simpler the biology, the more interesting the chemistry! The Scope of Natural Products
Although the term "natural products" would literally include any substance that occurs naturally, common agreement restricts its scope to those substances produced by living organisms, the original meaning of organic compounds. The components of petroleum, for example, are in general not natural products since they are believed to have resulted from the effectsof heat and pressure on the compounds produced by living organisms. The same is true for the components of coal tar, many of which are artifacts produced during the destructive distillation of coal. From the standpoint of structure, the classes of
compounds which are traditionally associated with the chemistry of natural products include alkaloids, carbohydrates, fats and fatty acids, proteins, steroids, terpenes, and numerous derivatives of heterocycles. Other simpler classes are often not discussed under the topic of natural products because they are discussed in the usual sequence of organic chemistry and since fewer examples occur naturally. These classes include simple alcohols, aldehydes, ketones, mereaptans, phenols, etc. Some classes are based on function rather than structure and often comprise a structurally heterogeneous group. Such classes as enzymes (proteins) and animal hormones (mainly proteins or steroids) are essentially structural classifications, but vitamins include a simple carbohydrate type of compound, steroids, terpenes, heterocycles, etc. All of these classes so far mentioned, which are generally recognized as natural products, are adequately discussed in textbooks (6) and in various treatises (7-13) and need only be mentioned to indicate the older and well-known types of structure which occur naturally. Table 1 gives representative examples of these classes. The remainder of this discussion is concerned with compounds not usually presented in the context of Table. 1 . Reserpine (alkaloid)
natural products; most of them have been investigated during the last fifteen years. Alkynes
The carbon-carbon double bond is of very common occurrence, particularly in terpenes and steroids. Polynnsaturation is also common, and the carotenoids, of which about 80 occur naturally, are mainly 40carbon terpenes containing 7 to 15 conjugated double bonds, usually all the tram configuration. It now appears that the triple bond, a t one time thought to be too reactive to occur naturally, is also common, for more than 115 naturally occurring alkynes have been isolated and characterized (IS, 14). The alkynes have been obtained from two major sources. Some 66 alkynes are 18-carbon acids found as glycerides in the seed fats of certaiq angio-sperms and in the essential oils of plants of Compositae. The others are produced by various species of higher fungi, mainly of the class, Basidiomycetes. Almost all of these compounds are polyacetylenes, and in addition they usually contain one or more ethylene or allene linkages (Table 2). Only alkynes of plant origin have a terminal double bond (24%) whereas only the alkynes of fungal origin have an allene linkage (27%). As
"Classical" Natural Products Saliein (alcohol)
CHI' CH1O-C 0
Sucrose (carbohydrate)
Muscone (ketone)
H Glyceryl
Vanillin (aldehyde)
OH
OH H
CH1-0-C(CHdtrCH3
/
1 I
0 mitostenrate oleOpaL (fat) CH-4-C--(CH?),,-CHa
tan (mercaptan)
II
Diallyl CHFCH-CH2-SS-CH9-CH=CH2 disulfide (disnlfide) CHI
Cholesterol (&wid)
I
HO
Vitamin A (ter pene)Volume 39, Number I , January 1 9 6 2
/ 3
Table 2.
Alkynes and Related Compounds Fungal origin
Nemotin H-(CEC)~CH=(XH-CH-
I
CHp I
Agrocybin HO--CH,-(C--C),CNH.
I1
0 Myoornycin
H-(C=CkCH=C=CH-(CH=CH)-CHI-COOH Plant origin
Tariri acid
CH~-(CH,),,C=C-(CH~),--COOH
Erythrogenic acid CH2=CH-(CHz)4-(Cd)ACH~kCOOH Matrioaria ester CH,CH=CH-(C=C)AH=CH-COCHt
II
0 Hexahydromatrioaria ester CH~CHz)4-CH=C=C=CH-C--OCHt
8
benzoquinones, naphthoquinones, and anthraquinones in animals (Table 3). The quinones have interesting biological actions, the antihemorrhagic action of the K vitamins being the most familiar example. Recently several terpenoid benzoquinones analogous to vitamin K have been isolated from the mitochondria of beef heart (17) and shown to act as coenzymes (Coenzymes Q ) in oxidationreduction processes (18). All have the same basic structure with variation in the length of the isoprene chain. A related henzoquinone with an isoprene sidechain has been found in plants (19). Plants of the genus H y p e r i m contain red, fluorescent pigments, the ingestion of which causes animals to become sensitive to light. This phenomenon, termed the "photodynamic effect," was first observed with acridines in 1897 and is well-known for certain synthetic fluorescent dyes. All known natural photodynamically active pigments, of which hypericin is an example, have been shown to he derivatives of a bisanthraquinone (helianthrone) ring structure (20,21). Several classes of natural products are derivatives of henzpyrones. The coumarins, of which more than 60 occur naturally, are derivatives of a-beuzpyrone (22). They occur in various parts of legumes, citrus fruits, grasses, and orchids; the parent compound, coumarin, has been isolated from 80 different species of plants. The only occurrence in animals appears to be the presence of 3:4-benzocoumarins in the scent glands of the beaver. With the exceptions of coumarin, hydrocoumarin, and dicoumarol, all natural coumarins Table 3.
would he expected from the high degree of unsaturation, most of these compounds are unstable, particularly in concentrated solutions or in the solid state, and difficulties are encountered in isolation, purification, and characterization owing to isomerization and polymerization. Although many polyacetylenic compounds are active against mycobacteria or fungi, none is clinically useful. Hexahydromatricaria ester, a compound related to matricaria ester, the most common plant alkyne, and occurring in the same species, is of interest, although not an alkyne, as an example of a naturally occurring cumulene.
Fumigatin
Vitamin KS
Chrysophanic acid
Quinones
More than 150 quinones have been isdated from plants and animals (15, 16). Although they constitute the largest class of natural coloring matters, their color is usually masked by other pigments or not obvious since the quinones are present in underground portions of the plant. The color of fungi is often due to quinones. In addition to higher plants and fungi, quinones also occur in certain insects and in the shells of marine animals. p-Benzoquinones, c- and pnaphthoquinones, anthraquiuones, and c-phenanthraquinones have been found in fungi and higher plants; benzoquinones and naphthoquinones in bacteria; anthraquinones and phenanthraquinones in lichens; and 4
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lournal of Chemical Education
Coensymes Q (Ubiquinonen)
Hypericin (a photodynamic pigment)
Quinones
coutain a 7-hydroxyl group and hence are derivatives of umbelliferone (7-hydroxycoumarin). The y-benzpyrones are known as chromonesif they do not contain aryl substituents (25). Only 11 chromones have been obtained, all from plants; the small number is believed to be due to the difliculties of isolation. They usually contain 2-methyl and 5-hydroxyl or 5alkoxyl groups. y-Benzpyrones with 2-aryl substituents are known as flavones, with 3-aryl substituents as isoflavoues (24). Over 70 flavones, 13 isoflavones, and several isoflavones containing additional hetero rings, excluding different glycosides of the same basic structure, have been isolated from plants, and nearly all have been synthesized. A very large number of related compounds are not benzpyrones but contain two benzene rings lmked by a 3-carbon bridge (e.g., chalcones, anthocyanidins) and are biogenetically related to the flavones and isoflavones (25). The term "flavonoids" is usually used to include the flavones, isoflavones, and these related compounds. Flavonoids occur in all parts of higher plants, but they have not been found in lichens or fungi. The only evidence for their presence in animals is their detection in butterfly wings, but the compounds are believed to be of exogenous origin. These compounds vary mainly in the number of hydroxyl or alkoxyl groups, which range from 0 to 7; they occur both in the free state and as glycosides. The structures of the parent benzpyrones and selected derivatives are given in Table 4.
Table 4.
Benzpyrones and Related Compounds Coumorins
R==H: Coumarin (5:6-bens-a-pyrone) -H:
Umbelliferone
Ellagic acid
Chromones
R,R',R"=H: Chromone
Flavones
Small Rings
While five- and six-membered rings seem to he the commonest in nature, both smaller and larger rings do occur. The cyclopropane ring occurs in steroids (26) and in several well-known terpenes (10, 26) such as aromadendrene, a sesquiterpene hydrocarbon component of eucalyptus (27). Only one fatty acid, lactohacillic acid (28), containing the cyclopropane ring is known, but several contain cyclopropene rings. Sterculic acid, from the oil of the Java olive, was the first naturally occurring cyclopropene to be found. Although the presence of a cyclopropene ring was first proposed in 1952 (ZQ), it was not unequivocally demonstrated until 1958 (SO), some 17 years after the first structural investigations. A second fatty acid containing cyclopropene, malvalic acid (Halphen acid), has been isolated from Malua vertkillata and M. paru$ora and has a structure similar to that of stercuiic acid with one less carbon atom ($1); a third acid, bombacic acid, not yet isolated in pure form, appears to be a cyclopropene derivative (92). Three- and four-membered heterocycles are also known. More than 50 epoxides (oxirans) are known (39, 54). The epoxide linkage occurs in fatty acids, terpenes, carotenoids, coumarins, quinones, alkaloids, steroids, and in large-ring compounds. The elucidation of the structures of compounds containing the epoxide group has been difficult because of intramolecular nucleophilic attack upon the epoxide linkage. The nitrogen analogs, ethylenimines (aziridines), have not been found in nature. Examples of four-membered heterocycles include the amino acid, azetidme-2carboxylic acid (ef. Table 9), norcardamine (Table 8), and penicillin, the first antibiotic (55).
Hibiscetin
R==H: Isoflavone (does not occur naturdy) -H: Daidzein
cH2 R-PYO,
CH3
I
Rotenone
\
OCHJ OCH,
Other Flovonoids
Delphinidin chloride (an anthocyanidin)
Volume 39, Number I, Jonuory 1962
/ 5
Table 5 contains the structures of typical smallring compounds. Table 5.
Small-Ring Compounds
X Lactobacillic acid
CHs-(CH&-CH-CH-(CH&oCOOH \/
Sterculic acid
Ca--(CH2)L?==c(CH&-COOH
CH:
1-Aminocyclopropane-1-csrboxylic acid Aeetidinez-earboxylic acid Linalo6l epoxide
derivatives, the most complex tropolones known, are of great interest since, in addition to having two sevenmembered rings and unusual chemical properties, they have long been known to have antimitotic activity and the ability to effect doubling of the chromosomes. The large cyclic ketones, muscone (15-membered ring) and civetone (17-membered ring), have already been cited as classical examples of natural products (cf. Table 1). Large lactones have been known since 1927, when the plant musks pentadecanolide and ambrettolide were characterized. Thirteen antibiotics are large-ring lactones or macrolides (41, 42) and several other antibiotics are probably also macrolides (43). These antibiotics are produced by various species of Streptomyces and have a large, highly substituted lactone ring usually attached to a dimethylamino-substituted sugar and occasionally to a second sugar. The size of the lactone varies from 12 members for methymycin and pikromycin to 17 for magnamycin, the most complex example, to 25 for pimaricin (44). Examples of large-ring compounds which occur naturally are given in Table 6.
Picrotoxin n Table 6. Large-Ring Com~oundr Guaiol
Stipitatic acid Penicillin hbeneyl, p-bydroxybenzyl, n-amyl, I-pent-2enyl
(CH,)d-CH-COOH I S
\
\Y
c%dc=O I
Colchicine CHsO
NH-C-R I1 0 Ambrettolide Large Rings
Seven-membered rings occur in terpenes, many of which contain a seven-membered ring fused to a fivemembered ring (bicyelo-[5.3.0]-decanes) and on dehydrogenation give rise to azulenes. Guaiol and vetivone are the best known examples. Dewar (56), in an ingenious explanation of the confusing experimental data on stipitatic acid, a mold metabolite, proposed a new type of aromatic ring system, tropolone, as the parent structure of this compound. Some 20 natural tropolones have since been identified (57, 58, 39). Colchicine (40) and its 6 / Journol of Chemical Education
Magnamycin
Sulfur-Containing Compounds
The well-known natural sulfur compounds include the mercaptans, sulfides, and disulfides. Interesting recent work on disulfides has involved a new Bs vitamin (45) and aureothricin and thiolutin (@), two examples of a new ring system. Various new functional groups involving sulfur are now known (Table 7). A nematicidal compound isolated from the roots of African marigolds and from the flowers of the common marigold has been shown to be &erthienyl; a closely related bithienyl occurs with this compound (46). The alkaloid zapotidine is a bicyclic derivative of thiourea (47). The thiazole ring occurs in thiamine (vitamin BI), the dipeptide portion of the antibiotic bottromycin (48), in firefly luciferin (49), and in two cardiac poisons from Calotropis Procera L. (50). Luciferin, which by euzymatic oxidation gives rise to light emission in the firefly, is also interesting in that it is a derivative of Dcyst,eine, whereas the naturally occurring amino acids of proteins and peptides have almost exclusively L configurations. Sulfate esters are common in animal t,issues, but a glucosyl diglyceride containing a sulfonic acid group, the first naturally occurring sulfonic acid, has just been reported (51). More than 30 glucosides which on hydrolysis produce isothiocyanates have been identified in the seeds of members of the family Cruciferae (52). The glucosides are actually derivatives of thiohydroximic acids, but rearrangement to isothiocyanates occurs on hydrolysis. Mustard oils, produced from mustard seed by enzymatic Table
7. Sulfur-Containing Compounds
Pyrrothine derivatives R=CHa:Thiolutin R=CIHs:Aureothriem
-1 CH,
Firefly Luriferin
HO S Zapotidine
Thiohydroximic glucosides
R-N=C=S rearrengemenf on hydrolysis
HO / 0 ~ 0 ~ 0 R=CH8, CnHs,-CH2-CH=CHs CSHEHZ,etc. H
xB~
k=k, (cH~)& a-Terthienyl
Glucose
x
6 so:
hydrolysis, are examples of isothiocyanates produced in this manner. Nitrogen-Containing Compounds
The classical natural products containing nitrogen contain either an amine or amide functional group. These include the simple amines found in decaying matter, the complex amines known as alkaloids, various heterocyclic nitrogen compounds, and the proteins or poly-amides. Recent investigations have elucidated the structures of some interesting heterocycles and of several new amino acids (to be discussed in the following section) which are not involved in proteins. The porphyrin nucleus has long been known to occur in combination with metal ions, such as copper, magnesium, or iron, in chlorophyll and as the prosthetic groups of hemoproteins, such as hemoglobin and the cytochromes, as well as in the free form (53). The exceedingly complex structure of cyanocobalamin (vitamin Bn), elucidated to a large extent by means of X-ray diffraction studies, contains an altered porphyrin nucleus complexed with cobalt (5455, 56). The altered porphyrin structure (one methine bridge is missing, so that two pyrrole rings are linked directly) presents an interesting biogenetic problem (57). About twelve derivatives of pteridine (1,3,5,8tetraazanaphthalene) occur naturally (58). Until recently they were regarded merely as insect pigmentsthe first pteridines were isolated from butterfly wings in 1891-but several are now known to be involved in the regulation of cell division. One of these, pteroylglutamic acid (one of several folic acids), is a B vitamin synthesized from p-aminobenzoic acid by bacteria but required preformed by mammals. The concept of metabolite antagonism, so important to the development of modern chemotherapy, resulted from the demonstration that the bacteriostatic action of the sulfa drugs is due to competition between the sulfonamide and p-aminobenzoic acid in the bacterial synthesis of pteroylglutamic acid. Very recently a reduced pteridine derivative that is light-sensitive has been found to be widely distributed in the eyes of amphibians and insects; it is assumed to be involved in visual processes (59). Phenoxazine (9-aza-10-oxaanthracene) derivatives are produced by Streptmyces and are exceedingly toxic antibiotics known as actinomycins (60). The 18 that have been characterized consist of two peptides joined to the phenoxadne ring system. Phenazines (9,lOdiazaanthracenes) have been found in another group of Streptmyces antibiotics, the grisoluteins (61). Pyrrole, previously known only combined in the porphyrin ring system or in its reduced forms, has been found as a complex Actinomycetes antibiotic, netropsin, containing 10 nitrogen atoms and the amidie linkage (68). But the most surprising result of recent studies has been the discovery of compounds containing various other nitrogen functional groups, several of them quite reactive and unstable, previously unknown in nature and not expected-by past standards-to occur naturally. The discovery in 1949 of a nitro group in chloramphenicol (chloromycetin), the first antibiotic to be synthesized on a commercial scale, marked the Volume
39, Number I, Jonuory I962 / 7
beginning of our knowledge of non-amino functional groups. 8-Nitropropionic acid, though isolated from glucosides of tree bark in 1920, was not identified until 1949; it has since been found in the free state in several plants and in certain fungi. Several derivatives of 10nitrophenanthrene have been isolated from Aristolochia clematis L. To date only these three basic structures containing the nitro group are known to occur naturally (6%). ,--,Other non-amino nitrogen functional groups of natural occurrence include the nitroso group (64), aliphatic azoxy group (66, 66), nitrile (67), diazo group (41, 68, 69), hydroxylamine (70, 71, 7t), and b i d e (73) (cf. Table 8). There are in fact five diazo compounds known, all of which have marked anti-
Table 8.
tumor
activity.
Two,
6-diazo-5-oxynorleucine
("DON") and azaserine, have been completely characterized, being derivatives of the amino acids leucine and serine, respectively. Hydroxylamine derivatives, in addition to the previously mentioned thiohydroximic acids, include 1amino-5-hydroxylaminopentane, a hydrolysis product of an incompletely characterized iron-containing antibiotic (70); a racemic trihydroxamate-iron(II1) complex, ferrioxamine B, a growth factor (70); norcardamine, a four-membered arnine fused to a nine-membered lactam (71); and cycloserine (oxamycin) (78), D4-amino-3-isoxazolidone, an optically active antibiotic which has attracted considerable interest because of its tuherculostatic activity (74). The naturally
Nifrogen-Containing Compounds
Cyanocohalamin (Vitamin Blr)
Chloramphenicol (Chloromycetin)
Elaiomycin
CHa(CHl)s-CH=CH-N=N-CH-CH-CH I 1 0 ?Ha OH
+
Pteroylglutamic acid (a pteridine)
e
OH H o o c - c m HI ~ - c H II- N H - c ~ N H - c H ~ ~ ~ ~ ~
COOH
NH2
Cycloserine
,N-H
NHz
0
Femoxamine B Actinomyoins (phenoxazines)
7
7'
,
NH9(CH,),~-C-(~~,)r~~~-
I U /I 0 0 (CHdrN-~CH,),C-NH-(CH2)I-~~-C~S I II I I1 II
eo
0 0
e
CH3
CH3
NH3
0
0 0
e
Fe +" (as octahedral complex of Fe; stereochemistry unknown)
R,R1=peptides
Actidione: R=Rf=R'=H Others: R ' s H , OH, OCCH,
8 8
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Journal o f Chemical Education
occurring imides are glutarimides isolated from Streptomyces and known as streptovitacins or cycloheximides. They are antibiotics with broad-spectrum antitumor activity, and one, Actidione (Cycloheximide), is commercially available as an antibiotic fungicide.
Table 9. New Amino Acids Plant origin Glutamic acid homologs HOOC-(CH2)syH--COOH
N e w Amino Acids
A few peptides have been discovered which contain amino acids previously unknown in nature. Thus etamycin, a macrocyclic peptide, contains eight amino acids, of which four are new (75). In 1947 it was shown that free amino acids exist in potatoes. As a result of this stimulus, not only have the protein amino acids been found in the free state in many plants, but a t least 30 new, non-protein amino acids have also been found (76,77), and there is evidence for a very large number of additional amino acids present in trace amounts. Many of the new amino acids are homologs or derivatives of the protein amino acids, but there is no evidence for their occurrence in proteins. Thus several P-substituted alanines occur in the seeds of watermelon and related plants, and the homologs of praline and glutamic acid have been found widely distributed. Other new acids, however, are not a-amino acids; thus y-aminobutyric acid and 8alanine both occur widely. With the exception of wide distribution of the four amino acids mentioned above, the others have generally been reported as constituents of only a few species of plants and appear to be peculiar to the species. Only a few amino acids have been obtained from animals, usually from diseased animals, and hence these amino acids probably reflect altered rather than normal metabolism. For example, a cysteine derivative, "isovalthine," has been isolated from the urine of hypercholesterolemic patients (78). Examples of the new, non-protein amino acids are given in Table 9. Halogen-Containing Compounds
It appears that organic halogen-containing compounds are uncommon in nature, although in view of the preceding discussion it should hardly be necessary to caution that this generalization may only reflect the limitations of our present knowledge. Iodine has long been known in the amino acid hormone, thyroxine, and in related iodine-substituted tyrosine derivatives. A bromine analog, 3,6dibromotyrosine, is present in the protein of the horny skeleton of certain corals. Chlorine occurs in the dichloroacetyl group of chloromycetin (cf. Table 8) and in a group of ether-lactones (depsidones) found in lichens (79, 80). Fluoroacetic acid has been shown to be present in the leaves of a South African plant known to be toxic to cattle (Sf), and the toxic component of the seeds of a related plant has been shown to be a fluoro-oleic acid, with traces of another long-chain fatty acid containing fluorine (88). Table 10 contains the structures of these halogen compounds. Variety of Structures from Related Species
Microorganisms have already been cited as the source of a very large number of the new chemical structures produced by living things. Van Tamelen
n
=
3,4
I
NHn r-Methyleneglutamic acid
HOOC-4-CH*-CH-COOH AHB
Cysteine derivative
I
NHz
CHAH-CHrS-CHAH-COOH
8
I
NHp
Animal origin Isovalthine
(CH&CH-CH-S-CH-CH-COOH 1 I COOH NH?
has surveyed the variety of stmctures produced by one group of microorganisms, the Actinomycetes (48); most of the compounds are produced by Streptomyeex species, and most have been discussed in this survey. A similar survey of the compounds obtained from lichens has been given by Asahina (83). Biogenesis and Function of Natural Products
Along with the isolation and characterization of natural products, the chemist is also interested in the pathways by which the compounds are synthesized within the living organism (biogenesis or biosynthesis) and the function of the compounds within the organism. Much information has been obtained about the biogenesis of many of the traditional classes of natural products, such as the terpenes, steroids, and alkaloids (85, 84, 86). Correlations of the compounds produced by related species of plants have been made; such a Table 10. Halogen-Containing Compounds Fluoroacetic acid
F-CHrCOOH
Chlorinecontaining depsidones
Thyroxine
H o ~ o ~ c H 2 - c H NH1 1 - c o o H
Volume 39, Number 1 , January 1962
/ 9
chemotaxonornic approach will certainly augment biological classification and, in theory a t least, may supplant the latter. The function of the wide variety of structures found in living organisms is an intriguing question which has been made even more challenging by the discovery of so many unusual types of structure. I n general there is speculation but no information regarding the function of these new compounds, and the notorious failure to deduce the function of so common and so long known a class of compounds as the alkaloids suggests that the function of many of the more recently discovered classes will probably remain unknown for some time.
(4) CONROY, H., J . Am. Chem. Soc., 79, 1727 (1957). L., Biol. Rev. Camb. Phil. Soe., 33, 396 (1958). (5) FONDEN, (6) FIN=, I. I,., "Organic Chemistry: Val. Two, Stereochemistry and the Chemistry of Natural Products," 2nd ed., Longmans, Green & Company, London, 1959. I
