Exploitation of natural products

The raison d etre of natural product diversity, and the exploitation of natural products by man, were delineated in Chapters 12 and 13. Man went further, in an endeavor to improve on nature by making available rare bioactive compounds and synthetic analogues with a better performance (Liu 1999). 

Apart from the immediate exploitation of natural products to satisfy our needs, there are several intellectual reasons for the employment of natural product chemistry. 

Tripathi R, Dubey N.K., 2004. Exploitation of natural products as an alternative strategy to control postharvest fungal rotting of fruit and vegetables Posthaverst Biol. Technol. 32 235-245. 

Five standard approaches to the generation of new areas for agrochemical (and pharmaceutical) research are commonly cited random screening speculative nthesis imitative ("me-too") chemistry biorational design and finally the exploitation of natural products (7). Although this last approach has found much commercial success in the development of novel insecticides (for example the pyrethroids), there are still relatively few examples of herbicides and fungicides which have been discovered in this way. This account describes the development of a new class of fungicides derived from the strobilurin family of natural products and related compounds, all of which are derivatives of P-methoxyacrylic acid. 

Commercial exploitation of natural products from the tropical forests may, in fact, be the only way to preserve this habitat and avoid its destruction by local inhabitants in search of conditions for survival or by commercial enterprises after a short to medium-term gain. A number of projects now under way indicate that rational exploitation is possible without permanent damage to the environment and scientific management of degraded areas may accelerate their recovery. 

For thousands of years, nature has provided humankind with a large variety of materials for the most diversified applications for its survival, such as food, energy, medicinal products, protection and defense tools, and others. The pharmaceutical industry has benefitted from such diversity of biomaterials and has exploited the use of natural products as sources of both drugs and excipients. One example of a promising biomaterial for pharmaceutical use is xylan, a hemicellulose largely found in nature, being considered the second most abundant polysaccharide after cellulose. 

Due to the interest of the accessible bicyclic systems in the field of natural products as potential precursors of terpenes, and to exploit the potentiality of... 

Dienes generated in this fashion can be trapped with dienophiles, either intramolec-ularly or intermolecularly, and this strategy has been exploited for the synthesis of natural products (equations 85 and 86)135,136. 

Several ingenious syntheses of natural products have been developed by exploiting benzcyclobutene ring opening to o-quinodimethane. Particularly, the intramolecular Diels-Alder strategy employing o-quinodimethane intermediates has been very effective for the construction of polycyclic structures. Selected examples are gathered in Table 12. 

Saponins are glycosylated secondary metabolites that are widely distributed in the Plant Kingdom.3,4 They are a diverse and chemically complex family of compounds that can be divided into three major groups depending on the structure of the aglycone, which may be a steroid, a steroidal alkaloid, or a triterpenoid. These molecules have been proposed to contribute to plant defense.3 6 Saponins are also exploited as drugs and medicines and for a variety of other purposes.4 Despite the considerable commercial interest in this important group of natural products, little is known about their biosynthesis. This is due in part to the complexity of the molecules, and also to the lack of pathway intermediates for biochemical studies. 

Chemists are exploiting catalytic C-H functionalization methodology for the synthesis of natural products or molecules of increasing complexity often with high degrees of regio-, chemo- and stereoselectivies. 

One cannot help but wonder whether this chemistry could be exploited in the assembly of natural products. For example, could the yield for formation of the linearly fused tricyclopentanoid 248, a structural unit common to many naturally occurring materials, be increased through the systematic variation of reaction conditions. ... 

The silylcuprate conjugate addition reaction has been used for the protection of an enone double bond, which can be regenerated with CuBr2 [22a], and for the strategic introduction of the silyl substituent for stereocontrol and regiocontrol purposes. Enantiopure 5-trimethylsilyl-2-cyclohexenone can be prepared by conjugate addition reaction [44] and the appropriate enantiomer has been converted into a number of natural products (Scheme 3.4) [38]. These synthetic strategies exploit... 

Application to both Type I and Type II intramolecular Diels-Alder cycloaddition has also met with appreciable success, the most efficient catalyst for these reactions being imidazolidinone 21 (Scheme 7) [51, 52]. The power of the inttamolecular Diels-Alder reaction to produce complex carbocyclic ring structures from achiral precursors has frequently been exploited in synthesis to prepare a number of natural products via biomimetic routes. It is likely that the ability to accelerate these reactions using iminium ion catalysis will see significant application in the future. 

The power of intramolecular Diels-Alder reactions have also been exploited in the synthesis of a number of natural products. MacMillan reported a concise and highly practical synthesis of solanpyrone D [51, 218] and Koskinen described an... 

The powerful directing effect of bis(isopinocampheyl) allylic boranes has been put to great use in the context of several applications of double diaster-ereoselective allylations in the total synthesis of natural products. As discussed in a previous section, the Brown allylation can be exploited to overcome the stereodirecting effect of chiral a-stereogenic aldehydes, including a-aUcoxy substituted ones. Thus, the simple allylation of aldehyde 154 provides as major product the desired diastereomer needed towards a total synthesis of brasilenyne (Scheme 14). The yield and stereoselectivity is even increased to over 97 3 under the low-temperature, magnesium-free conditions described before. 

Solid-phase synthetic methods1,2 feature convenient purification procedures coupled with opportunities for automation.3"5 These attributes have been widely exploited to prepare libraries of small molecules via parallel and combinatorial approaches. A logical extrapolation of these efforts is the supported syntheses of larger, more complex natural products and natural product analogs. Such efforts are consistent with the pharmaceutical industry objectives behind most high-throughput syntheses since, historically, the unique properties of natural products have provided a fertile ground for... 

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