Bioactive compounds, enhancing production

It may be concluded that PEF, HHP, and IR are adequate techniques for the retention of bioactive compounds in fruit and vegetable products and may even enhance bioactivity of juices, purees, and fresh-cut produce. A greater degradation of ascorbic acid in comparison with phenolics and carotenoids is usually observed. 

Numerous important bioactive compounds have been, and continue to be, isolated worldwide from natural sources. These compounds include both primary and secondary metabolites isolated mainly from plants, as well as from the animal and mineral kingdoms. The recent development of new bioassay methods has facilitated progress in the BDFI (bioactivity-directed fractionation and isolation) of many useful bioactive compounds from natural sources (1). These active principles could be developed or additionally modified to enhance the biologic profiles as clinical trials candidates. Many natural pure compounds have become medicines, dietary supplements, and other useful commercial products. This article summarizes research on many different useful compounds isolated or developed from plants with an emphasis on those discovered recently by the laboratories of the authors as antitumor and anti-HIV clinical trial candidates. 

This chapter has introduced the aldol and related allylation reactions of carbonyl compounds, the allylation of imine compounds, and Mannich-type reactions. Double asymmetric synthesis creates two chiral centers in one step and is regarded as one of the most efficient synthetic strategies in organic synthesis. The aldol and related reactions discussed in this chapter are very important reactions in organic synthesis because the reaction products constitute the backbone of many important antibiotics, anticancer drugs, and other bioactive molecules. Indeed, study of the aldol reaction is still actively pursued in order to improve reaction conditions, enhance stereoselectivity, and widen the scope of applicability of this type of reaction. 

Use of an integrated system incorporating CCC separation, PDA detector, and LC-MS proved to be a valuable tool in the rapid identification of known compounds from microbial extracts.6 This collection of analytical data has enabled us to make exploratory use of advanced data analysis methods to enhance the identification process. For example, from the UV absorbance maxima and molecular weight for the active compound(s) present in a fraction, a list of potential structural matches from a natural products database (e.g., Berdy Bioactive Natural Products Database, Dictionary of Natural Products by Chapman and Hall, etc.) can be generated. Subsequently, the identity of metabolite(s) was ascertained by acquiring a proton nuclear magnetic resonance ( H-NMR) spectrum. 

Engineering of novel natural products by enzymatic modifications of core skeletons is another method where molecular tools are used to produce a range of novel products with enhanced/modified bioactivity. This is mainly carried out because the distribution of many of these compounds are either restricted or they accumulate at low levels, which is insufficient for large-scale extraction... 

A number of investigations have been based on the conclusions of Strominger and Tipper [183,215]. It was estimated that by structural analogy between the terminal D-alanyl-D-alanine moiety of N-acetylmuramylpentapeptide and 6a-methylpenicillin the latter should possess an enhanced bioactivity. The first experiments aimed at obtaining this compound were unsuccessful [216,217], as the copper complex (112) could not be split after alkylation. Starting from 6-APA, Reiner and Zeller [216] were able to introduce the hydroxymethyl function into C-6, but the low activity of the end-product suggested the presence of (113) in the epi-conformation. The use 4>f formaldehyde yielded the spiro derivative (114). 

It was the ability to act as a plant own source for the resistance of cereals towzirds pests, which immediately caused a really interdisciplinary research directed on the understanding of all aspects of this imique class of natural products, which is often named hydroxamic acids or cyclic hydroxamic acids. We will rather shortly call them benzoxazinoids or benzoxazinones for the following reasons. Though most of them contain a cyclic hydroxamic acid and some the related lactam, it is only by the direct combination with the cyclic hemiacetal unit that these compounds receive their unique bioactive properties. As mentioned below, the bioactivity is clearly enhanced by a donor substituent in position 7. Hence, to avoid misinterpretations of the features responsible for biological effects, the neutral terms benzoxazinones or benzoxazinoids, are better suitable to name the class. 

A new method of bioactivity-directed fractionation, based on multidrug resistant pump (MDR) inhibition in Staphylococcus aureus, was reported for medicinal plants. This work resulted in the isolation, from berberine-containing Berberis species, two compounds that are themselves devoid of antibacterial activity, but that form potent synergistic couples with a sub-inhibitory concentration of berberine. The bacterial MDR pump inhibitors were identified as the flavonolignan 2 and the porphyrin 3 [98]. The isoflavones not only enhanced the antibacterial activity of the natural product, berberine. Fig. 4, but also the activity of synthetic... 

In 1986, Keller-Schierlein, ZShner and their respective coworkers isolated ( )-differolide (135, Figure 5.14) from cultures of an actinomycete, Streptomyces aurantiogriseus Tii 3149. This compound ( )-135, whose structure was determined by X-ray diffraction studies, was reported to enhance the formation of aerial mycelium and spores of Streptomyces glaucescens. Especially noteworthy was the fact that the natural product was racemic. There are some examples of the occurrence of racemic and bioactive natural products such as magnosalicin (10) and olean (116), but they are rare. Although there was a straightforward Diels-Alder synthesis of ( )-135 by dimerization of 2-vinyl-2-buten-4-olide, this method would not afford the enantiomers of 135. 

---