Organic isoprenoids

The isoprenoid compound shown is a scent marker present in the urine of the red fox Sug gest a reasonable synthesis for this substance from 3 methyl 3 buten 1 ol and any necessary organic or inorganic reagents... 

The organization of Part Two is according to structural type. The first section, Chapter Seven, is concerned with the synthesis of macrocyclic compounds. Syntheses of a number of heterocyclic target structures appear in Chapter Eight. Sesquiterpenoids and polycyclic higher isoprenoids are dealt with in Chapters Nine and Ten, respectively. The remainder of Part Two describes syntheses of prostanoids (Chapter Eleven) and biologically active acyclic polyenes including leukotrienes and other eicosanoids (Chapter Twelve). 

Isoprenoids or terpenoids are a large class of naturally occurring organic compounds with tremendous chemical and structural diversity. They are organic materials produced in the HMG-CoA (3-hydroxy-3-methyl-glutaryl-CoA) reductase pathway... 

A second major group of compounds associated with photosynthetic organisms are the carotenoids. These compounds are practically all derivatives of the same linear skeleton composed of eight isoprenoid (C5) units combined such that the two methyl groups at the molecular center are 1 6 to each other and other methyl groups are in 1 5 positions ... 

A hypothetical structural model developed by Yen (24) represented the organic components of Green River oil shale. The major components were isoprenoids, steroids, terpenoids and cartenoids. The common bridges consisted of disulfide, ether, ester, heterocyclic and alkadiene. Elemental analysis of typical oil shale samples has shown... 

Besides their essential roles in nature, isoprenoids are of commercial importance in industry. Some isoprenoids have been used as flavors, fragrances, spices, and food additives, while many are used as pharmaceuticals to treat an array of human diseases, such as cancer (Taxol), malaria (artemisinin), and HIV (coumarins). In contrast to the huge market demand, isoprenoids are present only in low abundance in their host organisms. Thus, isolation of the required isoprenoids consumes a large quantity of natural resources. Furthermore, owing to their structural complexity, total chemical synthesis is often not commercially feasible. For these reasons, metabolic engineering may provide an alternative to produce these valuable isoprenoids [88,89]. 

Larcher, A. V., Alexander, R., Rowland, S. J. and Kagi, R. I. (1986) Acid catalysis of alkyl hydrogen exchange and configurational isomerisation reactions acyclic isoprenoid acids. Organic Geochemistry 10, 1015. 

The isoprenoid hycrocarbons pristane and phytane (derived from the phytol side chain of chlorophyll), as well as porphyrins, have been detected in organic extracts of the Nonesuch Shale of 1.1 billion year age [23]. Their presence points to the existence of photosynthetic pigments in the Precambrian era, but it is also possible that these extractable substances could have been contributed to the rock at a later time. However, in this instance contamination appears to be less likely on account of the large abundance of organic material in this shale. 

Terpenes are a large and diverse class of compounds produced by a wide variety of organisms, though plants are an especially prolific source. The terms terpenoid and isoprenoid can be used interchangeably with terpene, though, strictly, terpenes are hydrocarbons (composed only of carbon and hydrogen) while terpenoids and iso-prenoids have been further functionalized. 

Previous methods for the preparation of salts of geranyl diphosphate and other allylic isoprenoid diphosphates are based on condensation between the alcohol and inorganic phosphate by trichloroacetonitrile as originally reported by Cramer and modified by Popjak The reaction generates a complex mixture of organic and inorganic polyphosphates which must be separated by chromatography. The desired diphosphate ester has been prepared on small... 

Orphan skeletons are emphasized in boldfece characters. Found both in the Tertiary and the Triassic eras, they have no equivalent in extant organisms and cannot be accounted for by di enetic transformations alone. They comprise xanthenoxanthene quinones, quincyte pigments of likely polyketide origin (Prowse 1991), and three series of isoprenoids polycyclic hydrocarbons from the... 

One current estimate of NP diversity totals ryo.ooo different structures, yet this huge chemical diversity is generated from only a few biochemical pathways that branch from the metabolism shared by most organisms. About 60% of the known NP diversity comes from one ancient pathway (the isoprenoids or terpenoids), another 30% comes from some other ancient pathways related to each other (the polyphenols, phenylpropanoids or polyketides) and less than 10% of NPs (alkaloids) comes from a more diverse family of pathways. There seems to be a rough correlation between the number of species possessing one pathway and the total diversity of NPs made by that route. Consequently, the minor groups of NPs that comprise less than 1% of the total NP diversity (e.g., the glucosinolates) tend to be restricted to a small number of species. 

Having produced many different carbon skeletons via the first phase of the isoprenoid/terpenoid pathway, the second phase of diversity generation occurs in all organisms when a number of versatile enzymes carry out a series of chemical additions, rearrangements and deletions by acting on different carbons in the basic skeleton. The... 

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]. 

In the past decade, eight inherited disorders have been linked to specific enzyme defects in the isoprenoid/cholesterol biosynthetic pathway after the finding of abnormally increased levels of intermediate metabolites in tissues and/or body fluids of patients (Table 5.1.1) [7, 9, 10]. Two of these disorders are due to a defect of the enzyme mevalonate kinase, and in principle affect the synthesis of all isoprenoids (Fig. 5.1.1) [5]. The hallmark of these two disorders is the accumulation of mevalonic acid in body fluids and tissues, which can be detected by organic acid analysis, or preferably, by stable-isotope dilution gas chromatography (GC)-mass spectrometry (GC-MS) [2]. Confirmative diagnostic possibilities include direct measurement of mevalonate kinase activities in white blood cells or primary skin fibroblasts [3] from patients, and/or molecular analysis of the MVK gene [8]. 

---