Stereochemistry and bioactivity

Synthesis, stereochemistry, and bioactivity of heterocyclic pheromones 97CC1153, 98CCC899, 98EJ01479. 

Mori K, Semiochemicals - Synthesis, stereochemistry and bioactivity. Eur J Org Chem 1479-1489, 1998. 

The relationships between stereochemistry and bioactivity among pheromones are diverse and far from straightforward. Organisms utilize chirality to enrich and diversify their communication systems.8,9 It must be emphasized that such diversity could be found only through experiments by using pure pheromone enantiomers of synthetic origin. In this section, several examples will be given to illustrate the diverse stereochemistry-bioactivity relationships. 

Since the stereochemistry of the triene system of LTB4 had not been determined prior to synthesis, a number of stereoisomers of LTB4 were prepared for purposes of definitive comparison of physical properties and bioactivity with biologically produced LTB4. The various stereoisomers of LTB4 were much less active biologically than LTB4 itself. 

Kozikowski, A.P., Tuckmantel, W., and George, C., Studies in polyphenol chemistry and bioactivity. 2. Establishment of interflavan linkage regio- and stereochemistry by oxidative degradation of an 0-alkylated derivative of procyanidins B2 to (R)-(—)-2,4-diphenylbutyric acid, J. Org. Chem., 65, 5371, 2000. 

Ariens, E. J. Stereoselectivity of bioactive agents general aspects. In Stereochemistry and Biological Activity of Drugs (Ariens, E. J., Soudjin, W., Timmermans, P. B. M. W. M., Eds). Blackwell Scientific Publications Oxford, 1983, pp. 11—32. 

Extensive joint works by biologists and chemists revealed that diversity is the keyword of pheromone response. I never dreamed of such diversity when I began my pheromone research. At present, this kind of diversity can be clarified only through experiments. It is therefore a prerequisite to study the relationship between stereochemistry (including cis/trans-isomerism) and bioactivity, if we want to use a pheromone practically. 

Soudijn, W. (1983) Advantages and disadvantages in the application of bioactive racemates or specific isomers as drugs. In Aribns, E.J., Soudijn, W. and Timmermans, P.B.M.W.M. (eds). Stereochemistry and Biological Activity of Drugs, pp. 89-102. Blackwell Scientific Publications, Oxford. 

It has been proven that palladium catalyzed reductive Heck reactions are versatile and high-yield approach for preparing of new bioactive alkaloid epibatidine (1) analognes fromN-benzoylated 2-aza-bicyclo[2.2.1]hept-5-ene (3) and it has been shown that in case of aryl- groups reaction progresses regioselectively. All Heck type reactions proceed exo-selectively, leading to the same stereochemistry as fonnd in 1. 

The first approach is shown in figure 3.1. This approach uses various techniques (e.g., alanine scanning) to identify the smallest peptide segment with biological activity within the overall peptide. This minimal bioactive segment may be cyclized or have its stereochemistry altered in order to attain restriction of conformational freedom and... 

Bioassay-directed fractionation of this plant led to the isolation of the known alkaloid verazine (16) and eight related compounds (six of them newly reported) as the bioactive constituents alkaloids 17 and 18 are examples of the new compounds isolated. The relative stereochemistry of the new alkaloids was established by careful ID- and 2D-NMR experiments. 

ABSTRACT The acid-catalysed epimerization reaction of bioactive indole alkaloids and their derivatives is reviewed. The three mechanisms, which have been proposed for the (J-carboline-type indole alkaloids, are discussed. Through recent developments, evidence for all three mechanisms has been obtained, which shows the complexity of the epimerization reaction. The epimerization seems to depend on structural features and reaction conditions making it difficult to define one universal mechanism. On the other hand, the isomerization mechanism of oxindole alkaloids has been widely accepted. The acid-catalysed epimerization reaction provides a powerful tool in selectively manipulating the stereochemistry at the epimeric centre and it can also have a marked effect on the pharmacology of any epimerizable compound. Therefore, examples of this reaction in die total synthesis of indole alkaloids are given and pharmacological activities of some C-3 epimeric diastereomers are compared. Finally, literature examples of acid-catalysed epimerization reactions are presented. 

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