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Part XXII | ||||||||||||||
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The bewildering array of natural products is difficult if not impossible to classify in a completely systematic and satisfying way. Natural products in this context are defined as those chemical entities produced by living organisms including plants, animals, and other not completely understood life forms. The field of biochemistry, given that name not even one hundred years ago by Carl Neuberg, is devoted to studying these natural products, their naturally-occurring derivatives and products of metabolism and degradation, and their roles in supporting life. The vast amount of knowledge about natural products gained in the meantime represents one of the most impressive accomplishments of human intellect, culminated recently by the elucidation, if not the interpretation, of almost the entire human genome of some 50,000 genes and 3 billion nucleic acids. The social problems arising from this new knowledge will be enormous, as exemplified by the patenting of thousands of human genes and the current dispute over their ownership in the case of Celebrex and the Cox-2 gene; this case alone could decide the fate of billions of dollars. White, Handler, and Smith in 1968 (Principles of Biochemistry, 4th Ed., McGraw Hill Book Company), saw biochemical interests classified into:
Lipids may be defined as animal or vegetable tissue components that are soluble in organic solvents, and more particularly in nonpolar organic solvents. They are therefore found chiefly in the fatty or oily constituents of organisms such as the human body. White, Handler, and Smith further classified the lipids as:
While this terminology may not be of compelling interest here, and may have been greatly supplemented in the intervening years, it is given here for reference and confirmation of proper English usage. Our immediate attention will be devoted to terpenes and steroids. Terpenes Henry Gilman in 1953 (Organic Chemistry, an Advanced Treatise, Vol. 4, p. 582) gave the following definition of terpenes: "The term terpenes originally designated a mixture of isomeric hydrocarbons of molecular formula C10H16 occurring in turpentine and many of the essential oils. At the present time the term refers to a large number of naturally occurring hydrocarbons of the formula (C5H8)n and to an even larger number of substances from natural sources that may be looked upon as being derived from such hydrocarbons in various states of oxidation and unsaturation. "The terpenes are usually classified according to the number of C5H8 units which they contain.
.... The most important structural feature that the terpenes have in common is their relation to the carbon skeleton of isoprene,
"The great majority of terpenes may by looked upon as derived from the carbon skeletons of dimers, trimers, tetramers, etc. of isoprene. The even divisibility of the carbon skeletons of terpenes into iso-C5 units is known as the isoprene rule and has been of tremendous value as a working hypothesis in the determination of structure." Myrcene (7-methyl-3-methylene-1,6-octadiene) is a typical monoterpene:
Myrcene is obtained chiefly from a-pinene by pyrolyis. a-Pinene in turn is the major constituent of turpentine, obtained by distillation from pinewood. Myrcene is used for the manufacture of perfume ingredients such as geraniol, nerol, linalool, citral, citronellol, citronellal, and ionones. Careful inspection of its structure will show that it can be considered to be derived from a head-to-tail combination of two isoprene carbon skeletons. a-Pinene, from turpentine, is a typical cyclic monoterpene:
It is used chiefly as a raw material for conversion to terpin hydrate (a medicinal expectorant used in cough medicines, and also used for conversion to perfume-grade terpineols). Although not completely obvious, the two isoprene skeletons comprise carbon atoms 8,9,6,5,7 and 1,10,2,3,4, respectively. Other monoterpenes closely related to myrcene and a-pinene are limonene:
and camphane:
Menthol, obtained from Japanese mint oil or by hydrogenation of thymol, is a saturated hydroxy compound with the same carbon skeleton as limonene. Camphor (obtained from camphor oil) and borneol are a ketocamphane and a hydroxycamphane, respectively. An important representative of linear sesquiterpenes is farnesol, with 15 carbon atoms in a head-to-tail isoprenoid series:
Farnesol is obtained from the essential oils of ambrette seeds and citronella. Kirk-Othmer, Encyclopedia of Chemical Technology, 2nd Ed., Vol. 14, pp. 193-214, Interscience Publishers, 1967, lists 156 kinds of essential oils obtained principally by steam distillation from plants, seeds, leaves, etc. In total, they are consumed in the thousands of tons annually, generally as odorants, perfumes, or flavors. An unusually interesting group of sesquiterpenes comprises compounds with 7-membered rings fused to 5-membered rings. The basic ring structure of one such group is exemplified by guaiazulene (1,4-dimethyl-7-isopropylazulene):
Azulenes exhibit resonance stabilization by the delocalization of electrons, in the same way as benzene and naphthalene. They are generally blue in color.
The triterpenes lead indirectly to the steroids, to be considered later. Straight-chain triterpenes are exemplified by squalene:
Squalene is a head-to-head combination of two head-to-tail trimers of isoprene. Another representation of squalene is:
This image makes apparent the structural relationship of squalene to lanosterol, a steroid:
Steroids are therefore derivatives of the four-ring system shown below, a dimethyl(cyclopentanoperhydrophenanthrene) system. The numbers shown in red are the conventional locants for naming steroids:
The most widely known of all steroids, cholesterol, is shown below with the conventional labels for rings A, B, C, and D:
A common method for designating unsaturation in steroids is Dn to indicate the first carbon atom of a double bond, with n designating its position. Cholesterol can thus be called D5-cholesten-3-ol. The interpolated -en-, of course, identifies unsaturation, while -an- would identify full saturation. The mysterious ways of nature are in full view with the terpenes and steroids. How they are produced by nature, how they function, why they are necessary for life, and how they can be put to use are all important questions to which we don't begin to know the full answers. We've come a long way, however, in just knowing their structures and in giving them unequivocal names. Many of them have now been synthesized from simple starting materials, and their structures are therefore certain. This accomplishment by pure reasoning, without the benefit of seeing these molecules visually, has to be considered a major miracle. |
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