Mixed terpenoids

Incorporations of [14C]isobutyrate, [I4C]isovalerate,398 and [14C]acetate399 into humulone (132) and derived compounds in Humulus lupulus have been reported. The first two are considered to be precursors of MVA, but the percentage incorporations recorded may not be meaningful, as adequate purification of the product was not carried out. As the location of tracer in the mixed terpenoid-polyketide was not determined, any biogenetic speculations must be tentative. 

Several important biomolecules are composed of nonterpene components attached to isoprenoid groups (often referred to as prenyl or isoprenyl groups). Examples of these biomolecules, referred to as mixed terpenoids, include vitamin E (a-tocopherol) (Figure 10.22a), ubiquinone (Figure 10.3), vitamin K, and some cytokinins (plant hormones) (Figure 11.11). 

Figure 14.11 illustrates the syntheses of phenylalanine, tyrosine, and tryptophan from chorismate. (Chorismate is also a precursor in the synthesis of the aromatic rings in the mixed terpenoids, e.g., the tocopherols, the ubiquinones, and plastoquinone.)... 

A further group of compounds having a mixed terpenoid biogenesis embraces a number of sesquiterpenoid derived antibiotics such as grifohn for which the revised structure XV has been advanced [120] and the related compounds... 

For the main part, the hterature survey encompassed by the present review covers the more readily accessible pubhcations from 1962 to May 1968, although in the case of certain compounds only recently recognised as having a terpenoid or mixed terpenoid biogenesis the coverage has been extended back beyond 1962 where appropriate. The opportunity has also been taken to amend inaccuracies and omissions in the earher review. 

The majority of natural products from tropical macroalgae are terpenoids (mainly sesqui- and diterpenoids), followed by acetogenins (acetate-derived compounds), and metabolites of mixed biosynthetic origin (such as meroditerpenes), frequently composed of terpenoid and aromatic portions (Blunt et al. 2007 and previous reviews see Chap. 1). 

Examination of the charts in Chapters 6.1.1 to 6.1.3 shows that the American and eastern tropical areas contribute more that the African tropics to the diversity of natural products. In particular the African tropics are poor in terpenoids, except secologanin, which is involved on a world basis in the formation of mixed-biogenesis alkaloids. 

Exposure of rat primary mixed hippocampal cell cultures to either sodium nitroprusside (SNP 100 xM) or 3-morpholinosydnonimine resulted in both a decrease in cell survival and an increase in free-radical accumulation. These SNP-induced events were blocked by either EGb 761 (10 to 100 pg/ml) or its flavonoid fraction CP 205 (25 pg/ml), as well as by inhibitors of protein kinase C (PKC chelerythrine) and 1-type calcium channels (nitrendipine). In contrast, the terpenoid constituents of EGb 761, known as bilobalide and ginkgolide B, as well as inhibitors of phospholipases A [3-[4-octadecyl)benzoyl]acrylic acid (OBAA)] and C (U-73122), failed to display any significant effects. Moreover, EGb 761 (50 pg/ml), CP 205 (25 pg/ml), and chelerythrine were also able to rescue hippocampal cells preexposed to SNP (up to 1 mM). Finally, EGb 761 (100 g/ml) was shown to block the activation of PKC induced by SNP (100 xM). These data suggest that the protective and rescuing abilities of EGb 761 are not only attributable to the antioxidant properties of its flavonoid constituents but also by their ability to inhibit NO-stimulated PKC activity (Figure 36.1). 

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 term meroterpenoids is generally used to denote a wide range of natural products of mixed (polyketide-terpenoid) biogenesis [121]. In our laboratory, the titanocene-catalyzed 6-endo/6-endo cyclization of 31, ob-... 

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. 

Scilla nervosa [ndwendwendwe, wild squill] (Burch.) Jessop. (Hyacinthaceae) bulb decoction is nsed for lower abdominal pains in women (26). The bulb contains alkaloids, cardenohdes, flavonoids, polyphenols, saponins, tannins and terpenoids (18). The bulb is also mixed with the roots of Crossandra fruticulosa Lindau [likhambilebantfwana, shade crossandra] (Acanthaceae) and then together used in treating peptic ulcers in children (12). 

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... 

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