Other Natural Cascades

The formation of /3-hydroxyselenides through the reaction of a selenium-stabilized carbanion with carbonyl compounds has been extensively used also in the context of natural product synthesis. The phenylselenoalkyllithium compound 115 was reacted with aldehyde 116 to afford /3-hydroxyselenide 117. In a radical cyclization cascade the tricyclic molecule 118 was generated in good yields and subsequent transformations led to the synthesis of pentalenene 119 (Scheme 28).1 9 Also other natural products like zizaene and khusimone have been synthesized via a similar route.200... 

OH) with aldehydes 9 in the homogeneous conditions (DMF or DMSO) (Scheme 10.1). Furthermore, PEG-supported catalyst 20a could be recovered by precipitation from the DMF solution with ether and reused in the same reactions without reduction of enantiomeric excesses of products 10 (R = OH). It also appeared applicable to asymmetric iminoaldol (Mannich) reactions to afford p-aminoketones 16 (R = Ar) (Scheme 10.3) and to the enantioselective Michael/aldol cascade reaction resulting in the S3mthesis of Wieland-Mischler ketone 28b, an important precursor of some other natural compounds (Scheme 10.6). Diastereo- and enantioselectivities of these reactions were close to the corresponding data for proline-catalysed reactions. 

Natural products are inherently bioactive. Bioactivity is a physiological response to a molecule or ion binding to a ligand, with downstream cascading consequences. Natural products are themselves products of enzymatic processes, demonstrating their ability to interact with receptors. Whether they bind other, nonsynthetic receptors likely depends on whether they have evolved in response to environmental pressures or whether they accumulate as a result of diverted primary metabolic pathways (Williams et al. 1989 Clardy 1995). 

A major cause of this problem in organic synthesis is the fact that many of the synthetic tools were developed without knowledge of how nature was performing its chemistry. We now have the heritage of many powerful chemical conversion procedures with a great variety in reaction conditions such as temperature, pressure, solvent, air and moisture sensitivity. In other words, procedures that as such are of great value but lack the possibility to be combined in a cascade mode of conversion for the multi-step syntheses frequently required for specialities. 

Using in vivo techniques, natural and synthetic fibrous materials have been shown to induce fibrosis and carcinogenic responses that were directly related to dose, if the materials were placed on the target tissues. Chrysotile appeared to be more biologically active than the other UICC asbestos samples or fibrous glass, with particle size and shape having some influence on the response. In vitro experiments indicate that fibers can be cytotoxic and possibly mutagenic, increase the secretory activity of fibroblasts, and possibly initiate an immune cascade. 

The cascade of biochemical events described above enhances the cellular necrosis and tissue breakdown, leading to what meat scientists and food technologist call meat-tenderization. Since muscle is primarily protein in nature and since hydrolytic, and specifically proteolytic, activity increases during postmortem aging, muscle represents a remarkable pool of material for the production of flavor peptides and amino acids as well as other precursors for flavor development (2). 

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