Polyketide origin

The acetate labeling results clearly demonstrated a polyketide origin for the naphthoate fragment. This resulted in the hypothesis that the first enzyme-free intermediate in azinomycin biosynthesis would be naphthoate 102, with condensation to fonn a polyketone chain, reduction, cyclization, and dehydration/aromati-... 

The framework of coccinelline-type alkaloids may be generated by linear combination of seven acetate units, as illustrated in Scheme 57 (330,336). An intermediate such as 456 would explain the existence of the different ladybug alkaloids. Support for the polyketide origin has been provided by feeding experiments ( " CHjCOONa and CHg COONa) with Coccinella septempunctata (330). 

Biosynthesis of adaline (107) may be carried out via intermediate 456 from polyketide origin. A possible biogenetic interrelationship between adaline (107) and the coccinelline-type alkaloids (Scheme 57), suggested by Tursch et al. 

Orphan skeletons are emphasized in boldfece characters. Found both in the Tertiary and the Triassic eras, they have no equivalent in extant organisms and cannot be accounted for by di enetic transformations alone. They comprise xanthenoxanthene quinones, quincyte pigments of likely polyketide origin (Prowse 1991), and three series of isoprenoids polycyclic hydrocarbons from the... 

Bartelt, R. J. and Weisleder, D. (1996). Polyketide origin of pheromones of Carpophilus davidsoni and C. mutilatus (Coleoptera Nitidulidae). Bioorganic and Medicinal Chemistry 4 429 138. 

The tetracyclines (Table 3.3) are a group of broad spectrum, orally active antibiotics produced by species of Streptomyces, and several natural and semi-synthetic members are used clinically. They contain a linear tetracyclic skeleton of polyketide origin in which the starter group is malonamyl-CoA (Figure 3.54), i.e. the coenzyme A ester of malonate semi-amide. Thus, in contrast to most acetate-derived compounds, malonate supplies all carbon atoms of the tetracycline skeleton, the starter group as well as the chain extenders. The main features of the pathway (Figure 3.54) were deduced from extensive studies of mutant strains of Streptomyces aureofaciens with genetic blocks... 

Metabolites from cyanobacteria are generally of amino acid or polyketide origin and frequently show potent biological activity. The series of dolastatin metabolites, exemplified by dolastatin-10 (Structure 2.18), are linear peptides which show potent cytotoxic activity and are of clinical interest as anti-tumour agents. Originally isolated in very low yield from the Indian Ocean sea hare Dolabella auricularia, dolastatins are now known to be cyanobacterial products.43,44 The discovery of a microbial source for these pharmaceutically important compounds will facilitate study of their biosynthesis and could potentially lead to the production of structural analogues by provision of modified biosynthetic precursors to the cultivar. As discussed below and in Section VI, toxic secondary metabolites from cyanobacteria have often been implicated in the chemical defenses of sea hares.45"17... 

Aromatic natural products of polyketide origin are less prevalent in plants compared with microorganisms. The majority of the plant constituents that contain aromatic stmctures are known to arise from the shikimate pathway (see below). Unlike those derived from the shikimate pathway, aromatic products of the polyketide pathway invariably contain a meta oxygenation pattern because of their origin from the cyclization of polyketides. Phenolic compounds such as chrysophanol-anthrone (Bl), and emodin-anthrone (B2), and the anthraquinones, aloe-emodin (B3) and emodin (B4) (Fig. 2), are products of the polyketide pathway and are found to occur in some plants of the genera Cassia (Leguminosae) (21), Rhamnus (Rhamnaceae) (22), and Aloe (Liliaceae) (23). The dimer of emodin-anthrone (B2), namely hypericin, (B5) is a constituent of the antidepressant herbal supplement, St. John s wort (Hypericumperforatum, Hy-pericaceae) (24). 

The anthraquinone 22, naphthalene 23a and the naphthoic acid amide 24 are respective constituents of the bacterial enediyne antibiotics dynemycin A, neocarzinostatin and kedarcidin (Scheme 5). [ C2]acetate feeding studies have established the polyketide origins of the anthraquinone nucleus 22 which is devoid of any carbon substituents and also the rare 1,8-disubstituted naphthalene 23a. ... 

Macrolides are secondary metabolites of polyketide origin [146-151]. The apparent similarity between macrolide and fatty acid biosynthesis was... 

Many arthropod pheromones are of putative polyketide origin, which are discussed in greater detail in Chapter 4.04. One noteworthy example is the novel 2,3-disubstituted /3-lactone, vittatalactone (73), recently characterized as a suspected male-produced aggregation pheromone for the striped cucumber beetle, Acalymma vittatum Vittatalactone is the first /3-lactone to be isolated from a beetle, and is only the third such structure to be characterized from an insect (Figure 24). 

The hypothesis that the Lycopodium alkaloids were of polyketide origin was advanced by Conroy at a time when only a few alkaloids of this family were known 43). By suitable combination of two 3,5,7-triketooctanoic acid chains in conjunction with a nitrogen source it is possible to account for the structures of the alkaloids of Chart 1. With the exception of luciduline the manner in which the two chains are considered to combine is implicit in the numbering system adopted for these alkaloids carbons 1 to 8 comprise one chain and carbons 9 to 16 the other. 

As mentioned, naphthylisoquinoline alkaloids are structurally unusual on account of the methyl group at the 3-position and oxygenation at the 8- and/or 6-position of the isoquinoline ring which points to a polyketide origin. This postulate has been supported by extensive studies conducted by Btingmann on the in vitro biomimetic synthesis of the naphthalene and isoquinoline portions of these compounds (ref. 13,14) and this work is worth briefly mentioning in a discussion on the total synthesis of these compounds. 

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