Historical Highlight Natural Products

Extraction of natural materials often produces complex mixtures of products, as described in the Historical Highlight at the end of this chapter, so additional operations are required to separate and purify individual compoimds. These procedures may involve techniques in which the compounds are separated on the basis of their acidic or basic properties (Sec. 5.3) or by chromatographic methods (Chap. 6). Thus, the isolation of pure natural products normally involves a series of complex and time-consuming operations. Fortunately there are some exceptions to this general rule. The isolation of trimyristin (20) from nutmeg is one of them. 

Historically, building up a library around a given core structure has been the first strategy to access natural product libraries. This approach is still the preferred way to prepare either focused libraries to study the SAR of certain natural products or to build libraries of very complex natural product scaffolds which cannot be constructed on solid phase yet. In Fig. 1 two notable structures of natural product libraries built by core structure modification are highlighted, such as an Indolactam library by Waldmann [72], and a Taxoid library by Xiao [73]. 

The existence of chirality in nature is of particular importance in numerous recognition processes, often illustrated by examples detectable by non-spectroscopic methods such as the different orange and lemon odors of R-(+)- and S-(-)-limonene, respectively (Fig. 3) [8]. As such, chiral discrimination is also of considerable consequence in the medical sciences, as often one enantiomer is pharmaceutically active whereas the other may show adverse side effects. A historic example is the anti-emetic activity of one of the enantiomers of thalidomide, while the other can cause fetal damage [9,10]. These considerations highlight the importance of chiral discrimination in the production of biologically active materials, whereas on the other hand, the design of routes to asymmetric synthesis presents an active challenge to synthetic chemists worldwide. 

As highlighted in previous reviews of nitrile hydratase, nitriles from both natural and industrial sources are a prevalent chemical functionality in our environment (i-5). In industry, nitriles find use in the production of fine chemicals, as pesticides, and as feedstock for the production of polyacrylamide and other polymers. Historically, waste products from these processes were dumped into open waterways or pumped into deep pressure wells, leading to deleterious environmental effects. Naturally occuring nitriles include... 

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