Sesquiterpenoid products

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).

Takeda, R., and K. Katoh Growth and Sesquiterpenoid Production by Calypogeia granulata Inoue Cells in Suspension Culture. Planta 151, 525 (1981). 

The sesquiterpenoid hydrocarbons (5)-a-curcumene (59) and (5)-xanthorrhizol (60) were prepared by asymmetric conjugate addition of the appropriate aryllithium reagent to unsaturated oxazoline 56 to afford alcohols 57 (66% yield, 96% ee) and 58 (57% yield, 96% ee) upon hydrolysis and reduction. The chiral alcohols were subsequently converted to the desired natural products. ... 

A modern variant is the intramolecular magnesium-ene reaction, e.g. the reaction of the alkene-allylic-Grignard compound 9 to give the five-membered ring product 10. This reaction proceeds regio- and stereoselectively, and is a key step in a synthesis of the sesquiterpenoid 6-protoilludene ... 

The terpenoid precursor isopentenyl diphosphate, formerly called isopentenyl pyrophosphate and abbreviated IPP, is biosynthesized by two different pathways depending on the organism and the structure of the final product. In animals and higher plants, sesquiterpenoids and triterpenoids arise primarily from the mevalonate pathway, whereas monoterpenoids, diterpenoids, and tetraterpenoids are biosynthesized by the 1-deoxyxylulose 5-phosphate (DXP) pathway. In bacteria,... 

Several examples of the monocyclic isothiocyano sesquiterpenoids having the bisabolane (83) skeleton are known. Along with the hydrocarbon theonellin (84), isothiocyanate 86 and formamide 87 were obtained from the Okinawan sponge Theonella cf. swinhoei. It seems remarkable, but not unusual, that not only was the amide the major constituent, but the isonitrile 85 was the missing member of the triad [57], Relative stereostructures were indicated by NMR analysis of theonellin formamide (87) and its transformation products. 

Very many naturally occurring 3-alkyl- or 3-acylfurans are now routinely synthesized by preparing a substrate for treatment with 3-furyllithium, itself made from 3-bromofuran according to Fukuyama, Tokoroyama, and Kubota, who used it to obtain pyroangensolide and fraxinellone.212 Equally, 2-lithiofuran is used for such natural products as the acetylenic furans from Alphonsea ventricosa213 and other compounds.214 For the synthesis of the sesquiterpenoid sponge-metabolite pleraplysillin-2 78, the lithiofuran 79 and therefore the bromofuran 80 was needed to secure the orientation a suitable preparation was devised for 80.215... 

Chlorophyta or green algae comprise one of the major groups of algae and include several exclusively marine orders and genera from tropical regions. Natural products chemistry research has identified more than 300 secondary metabolites from Chlorophyta, with most being sesquiterpenoid and diterpenoid compounds... 

The allylic oxidation of the sesquiterpenoid (+)-valencene has been performed using f-BuOOH as the oxidant and BiCl3 as catalyst. Nootkatone was the major product, isolated in 35% yield by flash chromatography (ethyl acetate - light petroleum, boiling point 40-60 °C) (Scheme 17) [87, 88]. 

Natural scents are exclusive products, used for the most highly-priced perfijmes. The largest market of perfumes - particularly in the poor developing countries - is based on synthetic materials. Natural scents are mostly derived from flower plants, evolved to be recognized by pollinating insects. The orchids (flower plants in the monocotyledonous family Orchidaceae, which make about 10% of all flower plants) are highly rated for scents, particularly the woody scent afforded by a sesquiterpenoid, caryophyll-5-en-2a-ol. 

These last years, several syntheses of natural products using an iron-catalyzed reaction of Grignard reagents have been published. In 1969, Meinwald and Hendry used the reaction discovered by Kharasch and Tawney to prepare an allenic sesquiterpenoid isolated from the grasshopper Romalea Microptera (Scheme 61). 

Methylene difluorocyclopropanes are relatively rare and their rearrangement chemistry has been reviewed recently [14]. In addition, electron deficient alkenes such as sesquiterpenoid methylene lactones may be competent substrates. Two crystal structures of compounds prepared in this way were reported recently [15,16]. Other relatively recent methods use dibromodifluoromethane, a relatively inexpensive and liquid precursor. Dolbier and co-workers described a simple zinc-mediated protocol [17], while Balcerzak and Jonczyk described a useful reproducible phase transfer catalysed procedure (Eq. 6) using bromo-form and dibromodifluoromethane [18]. The only problem here appears to be in separating cyclopropane products from alkene starting material (the authors recommend titration with bromine which is not particularly amenable for small scale use). Schlosser and co-workers have also described a mild ylide-based approach using dibromodifluoromethane [19] which reacts particularly well with highly nucleophilic alkenes such as enol ethers [20], and remarkably, with alkynes [21] to afford labile difluorocyclopropenes (Eq. 7). 

Volicifin has also been shown to activate a specific maize sesquiterpene cyclase gene, stcl, which is also activated in response to caterpillar feeding or regurgitant treatment (Shen et al., 2000). The transcription of stcl results in the production of a naphthalene-based sesquiterpenoid, which we have not yet detected from the many maize lines we have studied (e.g., Gouinguene etal., 2001). It would be interesting to see if this volicitin-induced substance shows attractiveness to natural enemies of the caterpillars that induce its production. 

Posadas, I., Terencio, M. C, Giannini, C, D Auria, M. V., and Paya, M. (2001). Dysidotronic acid, a new sesquiterpenoid, inhibits cytokine production and the expression of nitric oxide synthase. Eur. J. Pharmacol. 415, 285-292. 

Alkaloids are basic plant natural products that typically have a nitrogen atom as part of a heterocyclic ring system and indeed are classified on this basis. Thus major classes of alkaloids are based on indole, isoquinoline, pyrrolidine, piperidine, pyrrolizidine, quinoline, tropane, quinolizidine or other heterocyclic ring systems. Other alkaloids are basic monoterpenoid, sesquiterpenoid, diterpenoid, steroid, purine, pyrimidine or peptide entities. Some of these compounds are exceptionally toxic [1,6, 7-12]. 

Cyclopropanes are present in a variety of natural products and the intramolecular cyclopropanation sequence allows ready access to such compounds. The sesquiterpenoid antibiotic ( )-cycloeudesmol (53) was readily prepared from the monocyclic system (54 Scheme 9).91 Copper sulfate catalyzed decomposition of (54) generated the tricyclic system (55) with full control of stereochemistry. Further conversion of (55) to ( )-cycloeudesmol was achieved in four steps in 81% overall yield. A second example shown in equation (27)73 allowed access to (56), an important substructure of the antibiotic CC-1066. 

Collado and co-workers made detailed studies of the chemistry of the sesquiter-penoid caryophyllene and its hydroxylated products including rearrangements in-duced by superacids. They have recently reported novel rearrangements of the sesquiterpenoid panasinsane derivatives 213 to provide three products and interpreted the transformations by the involvement of the common carbocationic intermediate 214 [Eq. (5.304)]. 

Banwell MG, Edwards AJ, Harfoot GJ, Jolliffe KA, McLeod MD, McRae KJ, Stewart SG, Vogtle M (2003) Chemoenzymatic Methods for the Enantioselective Preparation of Sesquiterpenoid Natural Products from Aromatic Precursors. Pure Appl Chem 75 223... 

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