30 Natural Products
Broadly speaking, an organic natural product is a compound or mixture of compounds extracted from plant, animal, or (rarely) mineral substances. Usually the term refers only to substances of fairly complex structure. Although the isolation procedure may cause some chemical alteration, particularly hydrolysis, natural products are regarded in principle as pre-existent in the material from which they were extracted. For reasons that will appear later, natural products are usually designated by short nonsystematic names that do not describe their structures fully. Rules for assigning such names are far from comprehensive; they usually legalize trivial names and often deal with structural families rather than individual compounds. Because of the wide diversity of natural products and the specialized nature of their chemistry, no attempt is made in this chapter to give detailed rules and principles. In lieu of this, reference is made to selected publications providing up-to-date guidance for naming these materials, including official rules, tentative rules, and unofficial proposals. It is especially important to remember that in nearly all cases the short nonsystematic names that have been established for natural products are specific with respect to configuration—i.e., they refer to individual stereoisomers and are therefore not usually applicable to compounds synthesized in the laboratory. Recommended Nomenclature Practice Whenever practicable, a natural product should be designated by the systematic name for its structure; needless creation of new trivial names is undesirable. In the absence of other rules, the trivial name of a new natural product should be based on a material source or a property of the product and should bear an ending representing some aspect of its chemical structure, preferably the principal functional group. If this is unknown, the name should end in in (1). Lipids. Glycerides are preferably named systematically like other esters. The IUPAC-IUB (IUB stands for International Union of Biochemistry) Commission on Biochemical Nomenclature has recently promulgated definitive rules for naming lipids (2). Carbohydrates. The Rules of Carbohydrate Nomenclature approved 234
30.
Natural Products
235
by the American Chemical Society (3) are detailed, as are the more recent tentative rules published by the I U P A C Commission on the Nomenclature of Organic Chemistry and the I U P A C - I U B Commission (4) and the I U P A C - I U B tentative rules on cyclitols (5). There have been proposals to systematize the naming of dextrans (6), pectins (7), and mucopoly saccharides (8). A m i n o Acids, Polypeptides, and Proteins. Definitive rules for the nomenclature o f natural amino acids and related substances have been published by the I U P A C Commission (9, 10). Polypeptides are named by affixing the prefix names of the amino acid units in the sequence in which they occur to the name of the chain-terminating N-acylated amino acid. HOOCCHNH CH CH CONHCH(CH2SH)CONHCH2COOH 2
2
2
7-Glutamylcysteinylglycine Tentative rules for naming synthetic modifications of natural peptides have been established recently (11). Fully systematic names can also be applied to polypeptides, but this is much more cumbersome than the "consecutive u n i t " method. Protein structures are so complex that they are invariably designated by trivial names. Porphyrins. Porphyrins are derived from the structure shown, and may be named systematically as substituted porphines (12). H
CH
CH
Porphine In common practice, derivatives of porphine are called porphyrins—e.g., hematoporphyrin and the etioporphyrins. Nomenclature for the related corrinoids has been prescribed (13). Carotenoids. Tentative rules for nomenclature of carotenoids are available (9). Terpenoids. The naming of many monoterpene hydrocarbons is described by I U P A C Rules A-71 to A-75. These rules establish the names menthane, thujane, carane, pinane, bornane, norcarane, norpinane, and norbornane for parent compounds, and authorize the use o f a few trivial
236
NOMENCLATURE OF ORGANIC COMPOUNDS
names. They are derived from the much more detailed presentation in "System of Nomenclature for Terpene Hydrocarbons" (14). Similar lists of parent hydrocarbon names have been published for sesquiterpenes (i5), diterpenes (16), and triterpenes (17, 18), and derivatives of these may be named accordingly.
Cadinane (a sesquiterpene)
Abietane (a diterpene)
Phenolic Plant Products. Flavanoid compounds may be given various systematic or partially systematic names depending on selection of the parent compound. Thus Structure 1 may be called 2-(3,4-dihydroxyphenyl)3,5,7-trihydroxy-4H-l-benzopyran-4-one, 2-( 3,4-dihydr oxy phenyl)-3,5,7trihydroxychromone, 3,3',4',5,7-pentahydroxyflavone, or quercetin. The proposal of Freudenberg and Weinges (19) to establish Structure 2, called flavan, as a parent compound produces the name 3,3',4',5,7-pentahydroxyflav-2-en-4-one for 1.
l
30.
Natural Products
237
The lignans present a similar situation. The systematic name for (-) galbacin,Structure 3, istetrahydro-3,4-dimethyl-2,5-bis(3,4-methylenedioxyphenyl)furan, but this name does not define the stereochemistry.
3
If 2,3-dimethyl-l,4-diphenylbutane is defined as lignan, as proposed by Freudenberg and Weinges (20), and their stereochemical symbols are used, the name becomes (3,4) (3',4')-bis(methylenedioxy)-7,7'-epoxy-a7,08,i37'a8'-lignan. The nomenclature of tannins presents no special features. Nucleosides and Related Compounds. Names of these compounds may be based on those of the parent purines and pyrimidines: adenine, cytosine, guanine, thymine, and uracil. Steroids. These may be named by the recent "Definitive Rules for Nomenclature of Steroids" (18). Alkaloids. In spite of the magnitude and importance of this family, there is no system of nomenclature for these compounds as such. The recent IUPAC-IUB rules on steroids make some suggestions for naming alkaloids. Enzymes are named according to rules established by the International Union of Biochemistry (21). Vitamins are named either by systematic organic nomenclature or by rules established by the IUPAC-IUB (13). Discussion Because organic compounds were isolated and studied for many decades before an adequate structural theory and notation system were devised, the early nomenclature of natural products was completely nonsystematic—i.e., not descriptive of structure. The vast majority of natural products were named, and continue to be named, for their sources (22, 23). This may involve either the genus name, the species name, or the
238
NOMENCLATURE OF ORGANIC COMPOUNDS
common name of a plant or animal, or some other name of a naturally occurring material. Examples could be given by the hundreds: eugenol and caryophyllene from Eugenia caryophyllata (cloves), echinochrome A from the echinoderm Arbacia pustulosa, butyric acid from butter (Latin butyrum), uric acid from urine, and many others. Another type of trivial name for natural products is descriptive of some property of a designated compound. Thus sterols are named from Greek stereos, solid, and durene from Latin durus, hard, because these materials were early isolated as solids. Similarly, glycine, glycerol, etc. are named from Greek glykys, sweet, because of their taste. Very rarely, and fortunately so, natural products are named for persons or places: pelletierine for Pelletier, mexogenin for Mexico, and truxillic acid for Truxillo (Trujillo, Peru). Closely related substances have sometimes been named merely by adding a serial symbol to a family name: a-carotene, jS-carotene; vitamin A, vitamin B; protoporphyrin IX. Usually, as has happened for the vitamins, these names become displaced by better ones. There are at least two good reasons for continuing to assign trivial names to new natural products and to use such names for old and new ones. The isolation of a new compound from a natural source must precede determination of structure and sometimes does so by many years; during that time some means of designating the compound is required. Even when the structure has been established, the systematic name describing it is usually so complex (partly for stereochemical reasons) that chemists continue to use the trivial name. (The same convenience of brevity often leads to common names, often merely jargon, for synthetic compounds as well; compare drug names.) As systematic organic nomenclature has been developed, some of the old trivial names have been retained as official. For example, the Geneva conference adopted the methane, ethane, propane, butane sequence over the systematic monane, diane, triane, tetrane names. This principle of retention of well-established names has been adopted by the IUPAC, but it has been found necessary to make explicit the list of names thus retained; there is otherwise no definition of what is "well established." The expression of function in the names of organic natural products began early, first for acids and bases (alkaloids). The development of suffixes to designate function, which went on gradually in the nineteenth century (24), made this easier, and in 1924 the IUC (2) declared: "In the event of the constitution of a natural substance being too complex or not well known, the name with which it is to be designated should, at any rate, feature a termination in agreement with the principal chemical group." This dictum has been followed moderately well, but for one reason or another new natural products are still often assigned names ending in the
30.
239
Natural Products
noncommittal suffix in. Formerly this was confused with the ending ine, but the same IUC committee pointed out the need for reserving the ine suffix for basic substances. A recurring question is the desirability of elevating one or another coined name to approved status, or more frequently that o f assigning a parent name from which a family of natural products can be named systematically by the usual addition of affixes. F o r example, in the systematic naming of steroids (9), the hydrocarbon shown as Structure 4 is called 5/J-estrane. CH
3
H 4
Proposals for such systematization usually arise for families of natural products i n which development has been rapid and recent. A n I U P A C statement is apropos: " I f a new trivial name is created, any syllables in it that are used in systematic nomenclature must bear their systematic meaning and be used by the systematic methods." Unfortunately, however, the common practice of adding prefixes and suffixes to trivial names often is not definitive o f structure. F o r example, even i f the formula o f gibberic acid is known, the name ketonorallogibberic acid does not describe fully the structure of the derivative. Thus, care should be exercised to make sure that when trivial names are used as parent names, the principles o f systematic nomenclature are applied properly i n constructing names o f derivatives.
Literature Cited 1. J. E. Courtois, "Chemical Nomenclature," ADVAN. CHEM. SER., (1953) 8, 86. 2. "The Nomenclature of Lipids," European J. Biochem. (1967) 2, 127; Biochem. (1967) 6, 3287;J. Biol. Chem. (1967) 242, 2485. 3. "Rules of Carbohydrate Nomenclature," J. Org. Chem. (1963) 28, 281. 4. "Tentative Rules for Carbohydrate Nomenclature" (CNOC-CBN), Biochemistry (1971) 10, 3983; Biochem. J. (1972) 27, 741; and other places. 5. "The Nomenclature of Cyclitols," European J. Biochem. (1968) 5, 1; Biochem. Biophys. Acta (1968) 165, 1;Arch. Biochem. Biophys. (1968) 128, 269. 6. H. J. Koepsell et al., J. Biol. Chem. (1953) 200, 793. 7. F. A. Henglein, Makromol. Chem. (1953) 10, 89. 8. R. W. Jeanloz, Arthritis Rheumat. (1960) 3,233;Chem. Abstr. (1960) 54, 21211.
240
NOMENCLATURE OF ORGANIC COMPOUNDS
9. "Tentative Rules for the Nomenclature of Carotenoids (CNOC-CBN), Biochem. J. (1972) 127, 741; and other places. 10. "Addendum to Definitive Rules for the Nomenclature of Natural Amino Acids and Related Substances,''J. Org. Chem. (1963) 28, 291. 11. "Rules for Naming Synthetic Modifications of Natural Peptides. Tentative Rules" J. Biol Chem. (1967) 242, 555; Biochemistry (1967) 6, 362; Arch. Biochem. Biophys. (1967) 121, 6. 12. C. Rimington, Endeavour (1955) 14, 126. 13. "Nomenclature of Vitamins, Coenzymes, and Related Compounds," J. Biol. Chem. (1966) 241, 2987; Biochem. J. (1967) 102, 15; European J. Biochem. (1967) 2, 1. 14. "Nomenclature for Terpene Hydrocarbons," A D V A N . CHEM. SER. (1955) 14, 4. 15. F. Sôrm, Progr. Chem. Org. Nat. Prod. (1961) 19, 1;Pure Appl. Chem. (1961) 2, 533. 16. R. MCrindle, K. H. Overton, Advan. Org. Chem. (1965) 5, 47. 17. S. Allard, G. Ourisson, Tetrahedron (1957) 1, 277. 18. "Definitive Rules for Steroid Nomenclature," Pure Appl. Chem. (1972) 31, 283; and other places 19. K. Freudenberg, K. Weinges, Tetrahedron (1960) 8, 336. 20. K. Freudenberg, K. Weinges, Tetrahedron (1961) 15, 115. 21. "Enzyme Nomenclature Recommendations of the International Union of Biochemistry," Elsevier, New York, 1965. 22. M. P. Crosland, "Historical Studies in the Language of Chemistry," p. 287 Harvard University Press, Cambridge, 1962. 23. G. Bertrand, Bull. Soc. Chim. Biol. (1923) 5, 94. 24. M. P. Crosland, Bull. Soc. Chim. Biol. (1923) 5, 299.
