Polyketide-terpenoid metabolite

The Hajos-Parrish reaction can be regarded as the enantioselective version of the Robinson annulation. In the early stages of the synthetic effort targeting the mixed polyketide-terpenoid metabolite (-)-austalide B, L.A. Paquette and co-workers used this transformation to prepare the key bicyclic precursor in enantiopure form. Ethyl vinyl ketone was reacted with 2-methyl-1,3-cyclopentanedione in the presence of catalytic amounts of L-valine to afford the bicyclic diketone with a 75% ee. 

Signal transduction enzyme inhibition assays guided the isolation of two novel hybrid polyketide-terpenoid metabolites from a Penicillium sp. growing in the deepest waters (>750 ft) of Berkeley Pit Lake [9], Their structures were deduced by spectroscopic analysis and confirmed by single crystal x-ray analysis on berkeleydione (13). Both compounds inhibited signal transduction enzymes caspase-1 and matrix metalloproteinase-3. Berkeleydione (13) was also active against non-small cell lung cancer in NCI s 60 cell line anti-tumor screen. 

Biosynthetic studies have indicated a mixed polyketide-terpenoid origin for the unusual fungal metabolite andobenin (51) (Scheme 8). The two extra methyl groups ( ) are derived from methionine. Andobenin co-occurs with andilesin (52) whose structure has been recently elucidated by X-ray and c.d. analysis. ... 

The labelling studies described above provide definitive evidence for the mixed polyketide-terpenoid biogenesis of the andibenins, andilesins, andi-tomins, austin and terretonin. The formation of the bicyclo [2.2.2] octane system in the first two classes of metabolite provides a rare example of a biosynthetic Diels-Alder reaction. The biosynthetic relationship of austin and andibenin was supported by the isolation of austin from another mutant strain of A. variecolor [81]. Further metabolites related to austin have been isolated from Emericella dentata [82] and Penicillium diversum [81]. Other complex metabolites which are almost certainly further products of the meroterpenoid pathway are fumiga-tonin (102) and paraherquonin (103) which have been isolated from Aspergillus... 

Biosynthesis of polyketide-terpenoid (meroterpenoid) metabolites, andibenin A... 

The phytochemical diversity of C. saliva is well illustrated by more than 500 com-potmds isolated from this plant, encompassing all major classes of phytochemicals (polyketides, terpenoids, alkaloids, flavonoids, stilbenoids, oxylipins). Undoubtedly, the most important and peculiar secondary metabolites of C. saliva are cannabinoids, a class of mono- to tetracyclic C21 (or C22) meroterpenoids encompassing more than 100 members. These compounds are synthesized in secretory cells of glandular trichomes, most concentrated in unfertilized female cannabis flowers prior to senescence. A number of detailed accounts on the cannabinoid chemistry have been reported in the literature [6-8], also recently by Appendino et al. [9]. In this paragraph, we will provide an updated, although not comprehensive, account of the chemistry of this fascinating class of secondary metabolites. 

Figure 4 Halogenated terpenoid and polyketide metabolites isolated from red algae in the genera Laureucia and Plocamium...

Figure 11.1 Representative secondary metabolites produced by Streptomyces ceolicolor and other microorganisms, including aromatic polyketides actinorhodin and tetrohydroxynaphthalene (a), side-rophore desferrioxamines (b), polyunsaturated fatty acid eicosapentaenoic acid (c) and terpenoids beta-...

Extracts of Pterogorgia anceps contain a fraction enriched in ancepsenolide metabolites of the polyketide class, one of which (134) is individually deterrent in shipboard assays with T. bifasciatum 0 This last study illustrates that chemical defense mechanisms in gorgonians do not solely rely on the terpenoid biosynthetic pathway. 

Unlike primary metabolites, the genes that regulate the formation of the enzymes of seeondary metaboUte biosynthesis are often clustered. In several eases the loei of these genes have been determined. This has considerable sig-nifieanee in the control of secondary metabolite biosynthesis. The genes that eode for several important polyketide pathways such as those leading to the aflatoxins and the statins have been identified. Similar work has also been reported for penicillin biosynthesis and some non-ribosomal peptides as well as terpenoid pathways such as that leading to the gibberellins. 

Although it may be considered as a meroterpenoid (see Chapter 5) mycophenolic acid (4.32) is discussed here because its structure reveals the interaction between polyketides and terpenoids. A metabolite of a Penicillium species, which was probably mycophenolic acid, was first described by Gosic in 1896. It was more firmly characterized by Alsberg and Black in 1913 as a metabolite of... 

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