Common Reactions in Secondary Metabolites

The book is organized into seven chapters. In the introductory chapter, the synthetic pathways of some natural products illustrating the basic common reactions in secondary metabolites are described. In Chapter 2, methods and techniques involved in the biosynthesis of heterocycles are dealt with. The subsequent four chapters deal with three- to six-membered heterocycles starting from the natural products to approach the preparation of imnatural heterocyclic compounds with particular attention to bioactive molecules. In Chapter 7, seven- and eight-membered heterocycles are treated, as well as larger ones, using the same approach as used in the preceding four chapters. 

Like enzymes, whole cells are sometimes immobilized by attachment to a surface or by entrapment within a support. One motivation for this is similar to the motivation for using biomass recycle in a continuous process. The cells are grown under optimal conditions for cell growth but are used at conditions optimized for production of a secondary metabolite. A hollow-liber reactor, similar to those used for cross-flow filtration, can be used to entrap the cells while allowing input of the substrate and removal of products. Attachment of the cells to a nonreactive material such as alumina allows a great variety of reactor types including packed beds, fluidized and spouted beds, and air-lift reactors. Packed beds with a biofilm on the packing are commonly used for wastewater treatment. A semicommercial process for beer used an air-lift reactor to achieve reaction times of one day compared to five to seven days for the normal batch process. Unfortunately, the beer suffered from a mismatched flavor profile that was attributed to mass transfer limitations. 

In this section, some characteristic general reagents are described for a few of the most common types of natural products found as plant secondary metabolites (some of these are also listed in Chapter 10). It should be taken into consideration that none of these reactions is specific, and a positive reaction allows only the presumption of the presence of a certain type of secondary metabolite, since certain structural similarities with compounds of completely different types may result in false-positive reactions. A negative reaction does not exclude the presence of any compound by reason of the fact that such a compoimd may occur in too low a concentration for unambiguous detection. 

Cycloadduct (195) has been used in the synthesis of the C-nucleosides d-showdomycin (201) and D-3,4-0-isopropylidene-2,5-anhydroallose (202) via the common intermediate (203) (Scheme 5.66) [168]. The Diels-Alder endo cycloadduct (204), prepared in 50% yield and 92% diastereomeric excess by the reaction of (5 )-3-(2-pyridylsulfinyl)acrylate (194) with 3,4-dibenzyloxyfuran, was converted into the secondary metabolite (-)-shikimic acid (205) in six steps [169]. Cycloadduct (195), prepared as shown in Scheme 5.64, has also been transformed into (+)-methyl 5-epi-shikimate (206) [170] (Scheme 5.66). 

Biosynthesis of secondary metabolites involves numerous different mechanisms and reactions that are enzymatically catalyzed using several common mechanisms such as acylation, alkylation, decarboxylation, phosphorylation, hydride transfer, oxidation, elimination, reduction, condensation, rearrangement, and so on. The biosynthetic pathway may undergo changes due to natural causes (e.g., vimses or environmental changes) or unnatural causes (e.g., chemical or radiation) in an attempt to adapt or provide long life to the organism. 

As is true in other groups of secondary metabolites, several types of reactions follow the initial cyclizations addition and removal of hydroxyl and methoxyl groups, oxidation of methyl groups to alcohols, aldehydes, and acids, the reverse of this series, and decarboxylation. Decarboxylation of p-keto esters is especially common. 

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