Sesquiterpenoid biosynthesis

Zook M, Hohn T, Bonnen A, Tsuji J, Hammerschmidt R (1996) Characterization of novel sesquiterpenoid biosynthesis in tobacco expressing a fungal sesquiterpene synthase. Plant Physiol 112 311-318... 

The possible involvement of isomeric bisabolols in sesquiterpenoid biosynthesis has been investigated.24... 

Chappell, J., von Lanken, C., Vogeli, U. and Bhatt, P. (1989) Sterol and sesquiterpenoid biosynthesis during a growth cycle of tobacco cell suspension cultures. Plant Cell Rep., 8, 848-52. 

This chapter follows the pattern of previous Reports with the various sesquiterpenoids considered in structural groups based on their postulated or established biosynthesis. Interest in sesquiterpenoid structure, synthesis, and biosynthesis has continued at a high level during the period covered by the present Report. Two excellent reviews have been published one provides an up-to-date account of sesquiterpenoid biosynthesis while the other provides an authoritative description of studies on sesquiterpenoid stress compounds. Stress metabolites are produced by plants after infection with fungi, bacteria, and viruses or after mechanical wounding, irradiation with u.v. light, dehydration, cold, or treatment with phytotoxic agents. 

Chappell J, Nable R (1987) Induction of sesquiterpenoid biosynthesis in tobacco cell suspension cultures by fungal elicitor. Plant Physiol 85 469-473... 

Maier, W., B. Schneider et al. (1998). Biosynthesis of sesquiterpenoid cyclohexenone derivatives in mycorrhizal barley roots proceeds via the glyceraldehyde 3-phosphate/pyruvate pathway. Tetrahedron Lett. 39(7) 521-524. 

The structure of simularene (123), a new structurally interesting sesquiterpenoid isolated from soft coral (Simularia mayi), has been established by A-ray analysis. It has been suggested that the cyclosesquifenchene skeleton of simularene (123) is derived by rearrangement of the intermediate (122) proposed in the biosynthesis of a-and /8-copaene (124). 

Scheme 23. A schematic representation of the postulated involvement of a protoilludane intermediate (213) in the biosynthesis of various sesquiterpenoid...

Sesquiterpenoids based on the axane skeleton (354) have been reported previously as metabolites of marine sponges or algae (cf. Vol. 5, p. 77 Vol. 6, p. 89). Further investigations in this area have revealed the presence of axisonitrile-4 (355), axisothiocyanate (356), and axamide-4 (357) in the sponge Axinella cannabina. These compounds are A -derivatives of known metabolites (axisonitrile-1 etc.) of this sponge and are included in this section because their biosynthesis may involve rearrangement of a eudesmane precursor. 

The mevalonate-independent pathway is present in most bacteria and all phototropic organisms. In higher plants and most algae both pathways run independently. The mevalonate pathway is located in the cytoplasm and is responsible for the biosynthesis of most sesquiterpenoids. The mevalonate-independent pathway, in contrast, is restricted to the chloroplasts where plastid-related isoprenoids such as monoterpenes and diterpenes are biosynthesised via this pathway [43-45]. Figure 4.2 illustrates the interrelationships of both biosynthetic pathways connected to Fig. 4.1 [46]. 

Wunder A, Anke T, Klostermeyer D, Steglich W (1996) Lactarane Type Sesquiterpenoids as Inhibitors of Leukotriene Biosynthesis and Other, New Metabolites from Submerged Cultures of Lentinellus cochleatus (Pers. ex Fr.) Karst. Z Naturforsch 51c 493... 

The typical secondary metabolites of soft corals are diterpenoids, although some species also produce sesquiterpenoids. The sesquiterpene portion of furoquinol (Structure 2.102) is labeled by [2-3H]mevalonolactone in Sinularia capillosa,m while Heteroxenia sp. converts acetate and meva-lonate into cubebol (Structure 2.103) and clavukerin A (Structure 2.104).188 In contrast, acetate is used for cetyl palmitate synthesis in Alcyonium molle, but not for de novo diterpene biosynthesis.188... 

Figure 6.10 De novo biosynthesis of isoprenoid pheromone components by bark and ambrosia beetles through the mevalonate biosynthetic pathway. The end products are hemiterpenoid and monoterpenoid pheromone products common throughout the Scolytidae and Platypodidae (Figure 6.9A). The biosynthesis is regulated by juvenile hormone III (JH III), which is a sesquiterpenoid product of the same pathway. The stereochemistry of JH III is indicated as described in Schooley and Baker (1985). Although insects do not biosynthesize sterols de novo, they do produce a variety of derivatives of isopentenyl diphosphate, geranyl diphosphate, and farnesyl diphosphate. Figure adapted from Seybold and Tittiger (2003).

An excellent review of the isolation, structural elucidation, total synthesis, and postulated biosynthesis of sesquiterpenoids based on the spiro[4,5]decane (vetis-pirane) skeleton has been published." Further studies on the development of alternative routes to the vetispirane sesquiterpenoids have been described. In one report100 the spirocyclic acetal (217), previously used as an intermediate in the synthesis of (—)-a-acorenol (218),101,102 has been converted into (—)-agarospirol (219) and (-)-/3-vetivone (220) by the reaction sequence outlined in Scheme 26. 

A new sesquiterpenoid (317) isolated from the roots of a Turkish plant (Tanacetum species) has been assigned a structure whose biosynthesis may involve... 

Perforatone (46) and perforenones A (47 R = OH) and B (47 R = Cl) have been discovered in the marine alga Laurencia perforata.78 It is suggested that (46) and (47) are formed from a chamigrene cation (48), and this hypothesis provides a full rationale for the biosynthesis of the wide variety of sesquiterpenoids that have been isolated from Laurencia species. 

The pentalane class of sesquiterpenoids has received substantial attention in the past year from the standpoints of structural elucidation, biosynthesis, and synthesis. Two new metabolites of this class are pentalenic acid (298) and pentalenolactone H (299). Both these compounds have a secondary hydroxyl function adjacent to the gem-dimethyl group and are thus potential precursors of pentalenolactone (300) in which one of these methyl groups has undergone a 1,2-migration. Cane and Rossi " have now identified a further metabolite of a Streptomyces strain which has been named pentalenolactone E (301) and is now... 

Artemisinin is used here as an example of a plant sesquiterpenoid with both traditional value as well as with medicinal and social value in the twenty-first century. Research on artemisinin has also established new benchmarks for biochemical engineering and functional genomics of plant terpenoids. Artemisinin is a functionalized sesquiterpene with a unique peroxide linkage from the sweet wormwood Artemisia annua). Chinese herbalists have used it since ancient times, and it is now used for its unique efficacy to treat multidrug-resistant strains of the malaria parasite Plasmodium falciparum. Its medicinal importance has prompted studies into its biosynthesis and its biochemical engineering so that cost-effective methods for producing it in large scale and in consistent quality may be realized. 

Terpenoids, which are also known as isoprenoids, constitute the most abundant and structurally diverse group of plant secondary metabolites, consisting of more than 40,000 different chemical structures. The isoprenoid biosynthetic pathway generates both primary and secondary metabolites that are of great importance to plant growth and survival. Among the primary metabolites produced by this pathway are phytohormones, such as gibberellic acid (GA), abscisic acid (ABA), and cytokinins the carotenoids, such as chlorophylls and plastoquinones involved in photosynthesis the ubiquinones required for respiration and the sterols that influence membrane stmcture (see also Steroid and Triterpene Biosynthesis) (Fig. 1). Monoterpenoids (CIO), sesquiterpenoids (Cl5), diterpenoids (C20), and... 

Figure 1 Schematic overview of the biosynthesis of the monoterpenoids, sesquiterpenoids, diterpenoids, and triterpenoids. Representatives of these classes with biological relevance are shown. Enzymatic steps are indicated in italics DMADP, dimethylallyl diphosphate CDP, geranyl diphosphate GGDP, geranylgeranyl diphosphate FDP, farnesyl diphosphate IDP, isopentenyl diphosphate.

The biogenesis of many cyclic terpenoids requires a cts-double bond in the acyclic precursor. A cis-double bond is frequently incorporated into the terminal isoprenoid unit via an allylic rearrangement mechanism. Alternatively, a cis unit could be incorporated directly (as rubber). Two results this year highlight some features of this problem. Both geraniol (22) and nerol (23) are derived from all-trans units (i.e. retention of the 4i -proton of mevalonate) so that the cis-double bond of nerol is derived by isomerization. The sesquiterpenoid gossypol (34) is derived from c/s,cis-farnesyl pyrophosphate. Hence in its biosynthesis either... 

Furantriol (18.27), isolated from L. mitissimus (84), is one of the few lactarane sesquiterpenes in which one of the gem-methyl groups at C-11 is oxidized and it was chemically correlated (82) with lactarorufin B (11.71), another example of this kind. The Polish authors suggested that lactone 11.71 was enzymatically formed from furan 18.27, and that a C-15 oxidized sesquiterpene of the velutinal type was the common precursor of both compounds in the mushroom (84). Actually, the possibility for the C-15 methyl group to be oxidized at an early stage of the lactarane biosynthesis seems to be confirmed by the recent finding of C-15 hydroxylated protoilludane sesquiterpenoids (5.1 and 5.2) in L. violascens (23) (Table 5). 

The predicted involvement of brominated monocyclofarnesane derivatives in the biosynthesis of halogenated chamigrane sesquiterpenoids cf. Vol. 4, p. 96 Vol. 5, p. 55 Vol. 6, p. 64) has received considerable support by the recent isolation of a - (13) and /S-snyderol (14) from species of marine red alga (Laurencia obtusa and L. 

Prezizaene (119) and the related tricyclic sesquiterpenoids (120)—(122) have been isolated from Eremophila georgii. The absolute stereochemistry of these compounds is antipodal to that of the zizaene sesquiterpenoids found in vetiver oil cf. Vol. 3, p. 123 Vol. 4, pp. 94—96) and their biosynthesis probably involves cyclization of 8-acoradiene (115) and rearrangement of the intermediate allocedryl (116) or cedryl (117) carbonium ions or their biological equivalents cf. Scheme 14). ... 

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