Oh

orcinol ch3

orcinol ch3

3-methyl-2-cyclo-hexenone

Figure 4.3 Some further examples of acetogenins from insects. Mellein occurs in the mandibular glands and metapleural glands of ants. 3-Methyl-2-cyclohexenone comes from the pygidial glands of the ant Rhytidoponera chalybaea examples of very simple acetogenins, made by folding a polyketide composed of four units of acetic acid (Figure 4.2). It is now possible to see why the structure on the left in Figure 1.2 was predictable, while it is impossible to see how any simple polyketide can be folded to give

5-methylsalicylic acid.

The Australian ant Rhytidoponera aciculata produces 2-hydroxy-

6-methyl-acetophenone in its pygidial glands. Notice the similarity to 6-methylsalicylic acid. Other related acetogenins from insects are shown in Figure 4.3.

Given the structure of a substance we can usually work back to the polyketide from which it must be derived. When side chains occur in acetogenins, these are always derived from the 'tail' of the polyketide, never the carboxylic acid 'head'. The carbonyl oxygen nearest to the

this ß-keto-group is usually retained

Figure 4.4 The formation of an isocoumarin (produced by an Aspergillus mould), indicating the 'head' and 'tail' of the intermediate pentaketide this ß-keto-group is usually retained

Figure 4.4 The formation of an isocoumarin (produced by an Aspergillus mould), indicating the 'head' and 'tail' of the intermediate pentaketide endocrocin, a red pigment alternariol, a phenolic compound griseofulvin, antibiotic used of Aspergillus fungus from the fungus Alternaria tenuis for treating fungal infections

Figure 4.5 Further examples of products derived from polyketides. The head and tail of the polyketide are indicated endocrocin, a red pigment alternariol, a phenolic compound griseofulvin, antibiotic used of Aspergillus fungus from the fungus Alternaria tenuis for treating fungal infections

Figure 4.5 Further examples of products derived from polyketides. The head and tail of the polyketide are indicated carboxyl group in the polyketide is usually retained and is presumably necessary to activate the a-CH2 group for the cyclization (Figure 4.4). Some examples are given in Figure 4.5.

There are two types of polyketide synthase (known as PKS) enzymes. In type II polyketide synthases, the whole polyketide chain is first formed and then cyclized, oxidized or reduced as necessary, as in the examples above. Aromatic compounds like orsellinic acid, 6-methylsalicylic acid and isocoumarin are produced with type II synthases. In type I polyketides, each acetate unit is altered (reduced, dehydrated, etc.) as it is added, as happens in fatty acid synthesis (Figure 3.3). One of the difficulties in studying this type is the near absence of isolatable intermediates, since the growing chain remains attached to the polyketide synthase enzyme complex. The genes for the necessary enzymes are clustered together on one chromosome, and the process of synthesis is carried out on large complexes of enzymes. It is sometimes difficult to decide from looking at a structure whether it is derived from a fatty acid or from a type II polyketide. In the future it is possible this may be most easily decided by looking at the cluster of genes that code for the necessary enzymes.

2-Heptanone, a pheromone used by honeybees and many ants is a simple example of a type I polyketide. We can think of the compounds as being composed of a chain of acetate units as shown in Figure 4.6, which are joined together and then decarboxylated. The actual steps in its oooo <^0H -AqH -AQH

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