Biosynthesis of sesquiterpenes

The tens of thousands of known C15 terpenes derive from farnesyl pyrophosphate (5), which can be cyclized to produce about 300 different skeletal structures. The majority of known sesquiterpenes have been isolated from fungi, marine organisms and Streptomyces species, but a large number are also produced by flowering plants, where they serve a variety of functions. Like monoterpenes, many are found as components of essential oils. Other sesquiterpenes function as insect attractants, antifeedants or phytoalexins. 

Protonation-induced cychzation of germacrene A generates the cis-decalin skeleton of the eudesmyl cation, an intermediate in the biosynthesis of the phytoalexin capsidiol (79). The eudesmane skeleton is converted to the 5-epi-aristolochene (80) skeleton by Wagner-Meerwein rearrangements of a hydride and a methyl group (Cane 1990). Hydroxylation of 80 then produces capsidiol. The entire process of formation of epi-aristolochene from FPP is mediated by a single synthase which has been purified from tobacco (Starks et al. 1997). The intermediacy of germacrene A in the biosynthesis was demonstrated by mutation of 

The guaianes, like the eudesmanes, are derived from a further internal cychzation of germacrene A. The family includes matricin (81) and chamazulene (82), major components of the extract of German chamomile Matricaria chamomilla), which has anti-inflammatory properties (Castleman 2003). Related to the guaianes is the tricyclic sesquiterpene patchoulol (83), a perfumery raw material which is the major component 

The full details of sesquiterpene biosynthesis in chamomile are not yet known. Isolation of the prenyltransferase(s) responsible for the final steps in the biosynthesis and identification of the site of biosynthesis are likely to shed further light on the conundrum of biosynthetic compartmentation in flowering plants. These studies may also offer a challenge to the accepted wisdom that sesquiterpene biosynthesis in other flowering plants is always simply a matter of the processing of mevalonate-derived FPP in the cytosol. 

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Dumdei, E. J., Flowers, A. E., Garson, M. J., and Moore, C. J., The biosynthesis of sesquiterpene isocyanides and isothiocyanates in the marine sponge A canthella cavernosa (Dendy) evidence for dietary tranfer to the dorid nudibranch Phyllidiella pustulosa, Comp. Biochem. Physiol., 113A, 1385, 1997. 

The biosynthesis of sesquiterpenes in plants appears to be isolated from that of either monoterpenes or diterpenes. A prenyl transferase isolated from pumpkin Cucurbita pepo, Cucurbitaceae) converts C5 units into FPP, but not into gera-nylgeranyl pyrophosphate (the precursor to diterpenes). Another enzyme from the same source forms C20 terpenoids from C5 units, but does not accumulate lower homologs (also see Chapters 19 and 22). However, because famesyl pyrophosphate synthetase is a branch-point metabolite for the synthesis of sesquiterpenes, triterpenes, and sterols, this enzyme is ubiquitous in plants (Croteau and Johnson, 1985). 

Although many details of the biosynthesis of sesquiterpene lactones are not established, guaianolides, eudesmanol-ides, and pseudoguaianolides in the Asteraceae appear to be derived from germacranolide precursors (Fischer, 1978, 1990 Fischer et al, 1979). Biomimetic reactions leading to the formation of these and other types of sesquiterpene lactones have been proposed (Fischer, 1990). 

The Hiickel molecular orbital model and its applications in organic chemistry are discussed in a three-volume series of books. Heats of hydrogenation data have been collected and discussed in a useful short review Chemical Abstracts data retrieval has been covered through to the end of 1974. Allied to this is an extensive review of the nature of strain in organic molecules. Other major reviews deal with the biosynthesis of sesquiterpenes, the use of inductive substituent constants to assess the effect of polar substituents on organic reaction rates, and non-classical ions. ... 

Cane DE (1981) Biosynthesis of sesquiterpenes. In Porter JW, Spiugeon SL (eds) Biosynthesis of isoprenoid compoimds. Wiley, New York, Vol 1, p 283... 

As artemisinin has a terpenic structure, its biosynthesis starts in the formation of isopentenyl diphosphate GPP)> as in all the natural terpenoids. In plants, IPP is synthesized either via the mevalonate pathway in the cytosol or via the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway in the plastid. The IPP derived from the mevalonate pathway is generally used in the biosynthesis of sesquiterpenes (such as artemisinin), phytosterols, and triterpenes, and the IPP derived from the non-mevalonate pathway is employed in the biosynthesis of monoterpenes, diterpenes, and tetraterpenes (Fig. 89.15). 

When geranyl pyrophosphate reacts with isopentenyl pyrophosphate, the result is the 15-carbon famesyl pyrophosphate, which is an intermediate in the biosynthesis of sesquiterpenes such as famesene. Oxidation can then provide sesquiterpenoids such as famesol and juvenile hormone (Fig. 116.2). 

The biosynthesis of sesquiterpenes containing isonitrile and isothiocyanate groups was also investigated by incorporation of cyanide and potassium thiocyanate labeled with carbon 14 in the sponge Acanthdla cavernosa, which is consumed by the nudibranch Phyllidiella =Phyllidia) pustulosa. The results show that the mollusk does not synthesize de novo any nitrogen-containing terpene and consequently it acquires the sesquiterpenes substituted... 

Both 1,4- and 1,5-hydrogen rearrangements have been discovered in the biosynthesis of sesquiterpenes and diterpenes. A 1,4-hydrogen transfer occurs in the formation of the bicarbocyclic nucleus of the trichothecane sesquiterpenes, presumably via the parent hydrocarbon trichodiene 35, 207—209). The biosynthesis of helicobasidine, a closely related cuparene-type sesquiterpene, also has a 1,4-hydrogen rearrangement step 210). 

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