Terpenoid intermediates

Intermolecular.- Reviews have described some of the photochemical (2+2)-cycloaddition reactions of enones used in the synthesis of natural products. Other reports have also focussed on such additions as key steps in the design of natural products. Thus the photoadducts obtained by the cycloaddition of the enone (61) to the alkene (62) have been used as the starting materials for the synthesis of terpenoid intermediates. ... 

The major producers of the rose alcohols and citral have become so for a variety of reasons. Companies which manufacture wood and paper products produce sulfate turpentine or similar by-products rich in pinenes. They, or their subsidiaries, may then produce terpenoid fragrance materials from pinenes as a way of generating income from their by-product. Pharmaceutical companies which manufacture vitamins use terpenoid intermediates and so will often diversify into the manufacture of aroma chemicals. Their basic feedstocks are likely to be of petrochemical origin. Similarly, manufacturers of synthetic rubber possess technology for the use of isoprene as a feedstock and so are also likely to diversify into terpene aroma chemical manufacture. Fragrance companies will develop a position in terpenoid chemistry because of the importance of terpenoids as ingredients. 

D-Mevalonic acid is the fundamental intermediate in the biosynthesis of the terpenoids and steroids, together classed as poly-isoprenoids. The biogenetic isoprene unit is isopentenyl pyrophosphate which arises by enzymic decarboxylation-dehydration of mevalonic acid pyrophosphate. D-Mevalonic acid is almost quantitatively incorporated into cholesterol synthesized by rat liver homogenates. 

Since GAs as diterpenes share many intermediates in the biosynthetic steps leading to other terpenoids, eg, cytokinins, ABA, sterols, and carotenoids, inhibitors of the mevalonate (MVA) pathway of terpene synthesis also inhibit GA synthesis (57). Biosynthesis of GAs progresses in three stages, ie, formation of / Akaurene from MVA, oxidation of /-kaurene to GA 2" hyde, and further oxidation of the GA22-aldehyde to form the different GAs more than 70 different GAs have been identified. 

As exemplified in the present procedure, the reaction has been optimized and extended in scope it affords functionalized benzocyclobutenes as well as substituted isoquinolines in high yields. Benzocyclobutenes have been used as intermediates in the synthesis of many naturally occurring alkaloids, - steroids,polycyclic terpenoids,and anthracycline antibiotics. The traditional routes leading to the preparation of benzocyclobutenes have been... 

Another example of a nucleophilic acyl substitution reaction, this one a substitution by hydride inn to effect partial reduction of a thioester to an aldehyde, occurs in the biosynthesis of mevaldehyde, an intermediate in terpenoid... 

Cannabinidiol (CBND, 2.18) and cannabinol (2.19) are oxidation products of CBD and A9-THC formed by aromatization of the terpenoid ring. For the dehydrogenation of THC a radical mechanism including polyhydroxylated intermediates is suggested [10,11]. CBN is not the sole oxidation product of A9-THC. Our own studies at THC-Pharm on the stability of A9-THC have shown that only about 15% of lost A9-THC is recovered as CBN. 

Earlier work by Nancy Bucher showed an ATP requirement for cholesterol biosynthesis. The involvement of phosphorylated intermediates was established by Comforth, Popjak, and their associates in the early 1960s with the discovery of kinases which successively phosphorylated MVA to MVA-P and MVA-P to MVA-PP. MVA-PP was decar-boxylated and dehydrated to give the biological C5 isoprene unit, isopentenyl pyrophosphate. This undergoes successive head-to-tail condensations to give the linear 15C terpenoid, famesyl pyrophosphate. 

Snider and colleagues have developed the sequential ene reaction/thia-[2,3]-Wittig reaction which provide appropriately functionalized product 152 at allylic position on simple alkene 150 in two steps involving intermediate 151 (equation 87) . Thia-[2,3]-Wittig rearrangement was often utilized as a key step of natural product synthesis. Masaki and colleagues have demonstrated that the potassium enolate thia-[2,3]-rearrangement of aUyl sulfide 153 to 154 is useful for the synthesis of terpenoid diol component 155 of the pheromonal secretion of the queen butterfly (equation 88) . 

Polyene cyclizations have been of substantial value in the synthesis of polycyclic natural products of the terpene type. These syntheses resemble the processes by which terpenoid and steroidal compounds are assembled in nature. The most dramatic example of biological synthesis of a polycyclic skeleton from a polyene intermediate is the conversion of squalene oxide to the steroid lanosterol. In the biological reaction, the enzyme presumably functions not only to induce the cationic cyclization but also to bind the substrate in a conformation corresponding to the stereochemistry of the polycyclic product.21... 

Easily available advanced synthons, such as the carbohydrates, amino acids, hydroxyacids, and terpenoids, make the synthetic task easier than the complexity metrics of the target suggests this is especially true for the glycosides, if the carbohydrate portion can be introduced intactly. It must also be borne in mind that the S metric is counted in a linearly additive hion, neglecting interactions between the functional groups (Whitlock 1998) such interactions are not treated adequately by any method so far proposed to calculate the molecular complexity. Moreover, no attention was paid here to the graphic analysis of the synthesis plan based on the molecular complexity of the intermediates these aspects have recently been reviewed (Bertz 1993 Whitlock 1998 Chanon 1998). 

Methyl-5-hepten-2-one is an important intermediate in the synthesis of terpenoids. Its odor properties are not impressive. It occurs in nature as a decomposition product of terpenes. Tagetone [6752-80-3] is a major component of tagetes oil. Solanone [1937-45-8] and pseudoionone [141-10-6] are acyclic Cn ketones with a terpenoid skeleton. Solanone is one of the flavor-determining constituents of tobacco, pseudoionone is an intermediate in the synthesis of ionones. 

The reaction of a bis-alkynic alcohol (103) with aqueous dimethylamine gives dimethyl-aminofuran (104) (74IZV206). trans-Enynols cyclize presumably through a cis intermediate with base (75RTC70) or mercury(II) sulfate, a method used for the synthesis of the terpenoid bilabone (105) (69JOC857). 

Terpenoid alcohols, such as 25, are cyclized in superacids (FSO3H/SO2) under amixture of kinetic and thermodynamic control. Intermediate oxonium species were identified by 13C NMR59. 

IPP and DMAPP are reactive hemiterpene intermediates in the pathways leading to more complex terpenoid structures. They are also used as alkylating agents in the formation of meroterpenoids as indicated above, but examples of these structures are discussed under the section appropriate to the major substructure, e.g. alkaloids, shiki-mate, acetate. Relatively few true hemiterpenes are produced in nature, with isoprene, a volatile compound which is released by many species of plants, especially trees, being the notable example. Isoprene is formed by loss of a proton from the allylic cation (Figure 5.7). 

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