Diverse Sesquiterpenoids

The examples presented in this subchapter represent only a selected portion of the vast amount of literature publications highlighting the ability of cycloisomerization reactions to built structural diversity within the class of sesquiterpenoids. As the reaction mechanisms are refined and more things are currently known not only from palladium cycloisomerization chemistry but also from other unique pi-metals like gold and platinum, more impressive cascades are expected to flourish the chemical literature. Although cycloisomerization reaction is counting more than four decades from its concept discovery, we are convinced that it will stiU remain one of the best atom-economical methods for the construction of structurally comphcated natural products as those contained in the unlimited sesquiterpene family. 

Ghantous, H. Gali-Muhtasib, H. Vuorela, N. A. Saliha, N. Darwiche, Drug Discov. Today 2010,15, 66 -61S. 

Ansari, F. M. Doohan, Food Addit. Contam. 2005, 22, 369-378. 

Breitenstein, The Biosynthesis of My cotoxins A study of secondary metabolism P. S. Steyn (ed.), The Biosynthesis of Trichothecene Mycotoxins Academic Press (London), 1980, pp. 69-101. 

Jimenez-Nunez, C. K. Claverie, C. Nieto-Oberhuber, A. M. Echavarren, Angew. Chem. Int Ed. 2006,45, 5452-5455. 

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Diverse sesquiteipenoids Diverse sesquiterpenoid-like compounds... 

The diverse biological activity (allergenic, antitumour, fungitoxic, phytotoxic, cytotoxic, etc.) of germacranolides (226a and b) and other sesquiterpenoids containing cx/S-unsaturated y-butyrolactone units has been reviewed. During the period of... 

Sesquiterpenes are formed by the addition of one more isoprene units to a monoterpene molecule, and thus have the molecular formula C15H24 (see also Fig. 4.2). There are linear, branched or cyclic sesquiterpenes. Sesquiterpenes are unsaturated compounds. Cyclic sesquiterpenes may be monocyclic, bicyclic or tricyclic. They are the most diverse group among the volatile terpenoids [2, 3, 7-11, 13,14, 16, 20-24, 37-39, 49]. The DNP treats sesquiterpenoids in 147 different structural types [37]. Various types of sesquiterpenes (69-109) can also be seen in Structure 4.16. 

The Ci5 terpenoids known as sesquiterpenoids are the most chemically diverse group of terpenoids known in nature. Like monoterpenoids, many sesquiterpenoids contribute to the flavor and fragrances of a variety of plant products. To date about 10,000 sesquiterpenoids are known (32), and in the plant kingdom they commonly occur as hydrocarbons, alcohols, aldehydes, ketones, carboxylic acids, lactones, and oxiranes. The acyclic sesquiterpene hydrocarbons a- and p-farnesenes (HI and H2, respectively) (Fig. 8) are constituents of the oils... 

Figure 9 Cyclization modes of farnesane skeleton that lead to diverse monocyclic and bicyclic sesquiterpenoids.

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... 

In summary, these important investigations have rationalized the stereochemistry of the 1,3-hydride shift (which transfers a positive centre from C-10 or C-11 at the distal end of FPP to C-1 and so allows initiation of further isomerization or a second cyclization of the Cio or Ci i ring) on the basis of the ring size of the products. This presumably results from fixation of specific conformations of the intermediates on a hypothetical enzyme surface. The larger diversity of structure for sesquiterpenoids than for di- or tri-terpenoids could then reflect the larger conformational flexibility of a Cio or Cii ring (which are often involved in the formation of the former) than of the Ce rings that are usually implicated in the latter. 

The diverse biological activity (e.g. insect antifeeding, plant growth regulation, molluscicidal) of a number of drimane sesquiterpenoids has stimulated considerable interest in their synthesis and the year under review has seen many new developments and improvements. Much of the synthetic work has centred around the key bicyclic diester (54) derived from 1-vinyl-2,6,6-trimethylcyclohexene and dimethyl acetylenedicarboxylate. In contrast to earlier results,34 Ley et al.8S... 

Sesquiterpenes (sesquiterpenoids). A structurally highly diverse class of terpenoids with 15 carbon atoms skeleton derived biosynthetically from famesyl pyrophosphate (FPP) ( famesol, isoprene rule, ter-penes). More than 70 different ring systems are formed by enzyme-catalyzed cyclization of the linear parent structure these cyclic structures can be further modified by 1,2- and 1,3-hydride shifts, renewed cycliza-tions, hydroxylations, and other subsequent reactions. S. are widely distributed in plants, fiingi, and animals but are less common in bacteria. Specific biosynthetic routes are often characteristic for certain organisms. Thus, basidiomycetes preferentially use humulene as the basis for the syntheses of protoilludanes, illu-danes, lactaranes, hirsutanes, and related S. skeletons. Individual S. systems are also known for liverworts and marine organisms. In addition, liverworts often contain the optical antipodes of S. known from plants. 

FIGURE 2.2 The biosynthesis of terpenoids provides an excellent example of achieving skeletal diversity. The single precnrsor famesyl pyrophosphate gives rise to all sesquiterpenoids. Only five of the many known sesquiterpenoid ring skeletons are Ulnstrated here. 

Presently, sesquiterpenoids (128, 237, 305, 333, 376) constitute the largest single class of terpenoids, with over 2500 well-defined (only C15) compounds, embracing some 120 distinct skeletal types from acyclic to tetracyclic. Sesquiterpenoids encompass a most impressive array of carbocyclic ring systems, and this diversity and novelty have stimulated outstanding synthetic activity in this field (184). Figure 8.1.8 depicts the important sesquiterpene skeletal types most widely distributed in nature and often encountered as constituents of wood extractives. 

Apart from the diversity presented by their core structures, sesquiterpenes are commonly decorated with lactone moieties and hydroxyls throughout the basic core. Thus, usually isolated biologically active natural sesquiterpenes are highly oxidized, referred in the literature as sesquiterpe-noids. The a,p-unsaturated lactone functionality is a common feature of many cytotoxic sesquiterpenoids accounting as a powerful alkylating side through a Michael-type addition to suitable biomolecules as the cysteine residues on proteins and enzymes. Thus, several biological active sesquiterpenoids have been isolated and used in traditional and modem... 

These biosyntheses are only indicative examples of the structural diversity that can be achieved by sesquiterpene synthases on the synthesis of sesquiterpenoids. Summarizing this multistage process, the biosynthesis begins by the synthesis of FDP, the major precursor of all sesquiterpenoids, through prenyltransferase. Sesquiterpene synthases are then... 

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