Background

I do not know what I may appear to the outside world, but to myself I seem to have been like a boy playing on the sea-shore, and diverting myself in now and then finding a smoother pebble or a prettier shell than ordinary, whilst the great ocean of truth lay all undiscovered before me.

Isaac Newton

Using a simple five carbon building block, nature creates an array of terpenoid chemicals with an infinite variety of structural variation and vast range of biological functions. Such a cornucopia cannot but leave the terpene chemist feeling as Newton did.

KEY POINTS

The simple isoprene unit is the basis of an enormous range and a variety of chemical structures which we know as terpenoids.

In nature, terpenoids serve a variety of purposes including defence, signalling and as key agents in metabolic processes.

Terpenoids have been used in perfumery, cosmetics and medicine for thousands of years and are still extracted from natural sources for these uses.

1.1 DEFINITIONS AND CLASSIFICATION

Plants and animals produce an amazingly diverse range of chemicals. Most of these are based on carbon and so the chemistry of carbon came to be known as organic chemistry, i.e. the chemistry of living organisms, the chemistry of life. These chemical products of plants and animals can be classified into primary and secondary metabolites. Primary metabolites are those which are common to all species and can be sub-divided into proteins, carbohydrates, lipids and nucleic acids. These four groups of materials are defined according to the chemical structures of their members. The secondary metabolites are often referred to as "natural products". These can be sub-divided into terpenoids, alkaloids, shikimates and polyketides. This classification is based on the means by which the materials were made. These synthesis routes are referred to as biosynthetic or biogenetic pathways.

Individual secondary metabolites may be common to a number of species or may be produced by only one organism. Related species often have related patterns of secondary metabolite production and so a species can be classified according to the secondary metabolites they produce. Such a classification is known as chemical taxonomy. Occasionally, two plants are found to have identical physical aspects which botanists use for classification, but differ in the secondary metabolites they produce. For example, two flowers may look identical but one is odourless whilst the other possesses a strong scent due to the production of a fragrant terpenoid chemical. Such different strains are known as chemotypes.

Terpenoids are defined as materials with molecular structures containing carbon backbones made up of isoprene (2-methylbuta-1,3-diene) units. Isoprene contains five carbon atoms and therefore, the number of carbon atoms in any terpenoid is a multiple of five. Degradation products of terpenoids in which carbon atoms have been lost through chemical or biochemical processes may contain different numbers of carbon atoms, but their overall structure will indicate their terpenoid origin and they will still be considered as terpenoids.

The generic name "terpene" was originally applied to the hydrocarbons found in turpentine, the suffix "ene" indicating the presence of olefinic bonds. Each of these materials contain two isoprene units, hence ten carbon atoms. Related materials containing 20 carbon atoms are named as diterpenes. The relationship to isoprene was discovered later, by which time the terms monoterpene and diterpene were well established. Hence the most basic members of the family, i.e. those containing only one isoprene unit, came to be known as hemiterpenoids. Table 1.1 shows various sub-divisions of the terpenoid family based on this classification. It also shows two specific sub-groups of terpenoid materials, namely, the carotenoids and the steroids. Steroids and carotenoids are sub-groups of the triterpenoids and tetraterpenoids, respectively, as will be explained later.

Occasionally, the word terpene is used to indicate any terpenoid. In this book, the word terpene will be restricted to its original meaning. Similarly, the term "isoprenoid" is often used in place of "terpenoid."

1.2 THE ISOPRENE RULE

The isoprene rule, proposed by Wallach in 1887, defines terpenoids as chemicals containing a carbon skeleton formed by the joining together of isoprene units. Isoprene, the "building block" of terpenoids, is 2-methylbuta- 1,3-diene. If we look at the parent 2-methylbutane, we could consider the molecule to resemble a nanoscalar tadpole with a "head" at the branched end of the molecule, the other end therefore constituting the "tail." Thus, in principle, two isoprene units could be joined head-to-head, tail-to-tail or head-to-tail. By far the commonest fusion is head-to-tail. Figure 1.1 shows two isoprene units being joined head-to-tail to produce a monoterpenoid backbone. Occasionally, a tail-to-tail coupling occurs. This is a characteristic feature of steroids and carotenoids. In both of these classes, there is a tail-to-tail fusion exactly in the centre of the backbone, the other joins being head-to-tail type. The hypothetical head-to-head fusion does not occur.

After formation of the basic C5n skeleton, the chain may be folded to produce rings and functionalised by the introduction of oxygen or other heteroatoms. Figure 1.2 shows how the isoprene units and the original backbone can be traced out in three simple terpenoids. Occasionally, skeletal rearrangements occur which make this process more difficult and fragmentation or degradation reactions can reduce the number of carbon atoms so that the empirical formula does not contain a simple multiple of five carbons. Nonetheless, the natural product chemist will still quickly recognise the characteristic terpene framework of the structure. Sometimes molecules contain both terpenoid fragments and fragments from other biogenetic classes.

1.3 TERPENOID NOMENCLATURE

The terpenoids are divided into groups and sub-groups according to the pathway by which nature synthesised them and hence, by their skeletal structures since these arise directly from the biosynthesis. As described above, the first basis for classification is the number of isoprene units which make up the terpenoid. The names for these groups are shown in Table 1.1. The next classification depends on whether the skeleta remain as open chains or have been cyclised giving one, two or more rings. Families of terpenoids possessing the same skeleton are named after a principal member of that family, usually either the most common or the first to have been discovered. Charts of these names are given in Devon and Scott's dictionary. To...