Structure-activity relationships transfer mechanisms

Cationic polymerizations induced by thermally and photochemically latent N-benzyl and IV-alkoxy pyridinium salts, respectively, are reviewed. IV-Benzyl pyridinium salts with a wide range of substituents of phenyl, benzylic carbon and pyridine moiety act as thermally latent catalysts to initiate the cationic polymerization of various monomers. Their initiation activities were evaluated with the emphasis on the structure-activity relationship. The mechanisms of photoinitiation by direct and indirect sensitization of IV-alkoxy pyridinium salts are presented. The indirect action can be based on electron transfer reactions between pyridinium salt and (a) photochemically generated free radicals, (b) photoexcited sensitizer, and (c) electron rich compounds in the photoexcited charge transfer complexes. IV-Alkoxy pyridinium salts also participate in ascorbate assisted redox reactions to generate reactive species capable of initiating cationic polymerization. The application of pyridinium salts to the synthesis of block copolymers of monomers polymerizable with different mechanisms are described. 

Since 1946, a series of antibiotic antimycins A (AA, 94-la 94-9) have been isolated from various Streptomyces species [77-80] (Fig. 5). Antimycin A complex, a mixture of derivatives, has been widely used for biochemical studies. As it inhibits the electron transfer of ubiquinol-cytochrome c ox-idoreductase [81], many scientists have investigated their structure-activity relationships and mechanism of action [82-89]. The related deacyl compounds, deisovalerylblastmycin (95a) [90], urauchimycins 95b and 95c [91], and kitamycins 95d and 95e [92] were isolated from Streptomyces species. In addition, the corresponding L-serine derivatives, UK-2A 2D (96a-d) [93] and UK-3A (97) [94], were added to this series. 

Kovacic P, Pozos RS, Somanathan R, Shangari N, O Brien PJ. Mechanism of mitochondrial uncouplers, inhibitors and toxins Focus on electron transfer, free radicals and structure-activity relationships. Curr Med Chem 2005 12 2601-23. 

Cordova et al. demonstrated in 2005 that the aldol condensation between 4-nitrobenzaldehyde (5 R=p-N02) and cyclic ketones or butanone in the presence of acyclic primary amino acids led to the antz-isomer 6 (Scheme 12.3). One year later, this author described the structure-activity relationship between acyclic amino acids and the aldol derivatives, the synthetic scope of catalysis by acyclic amino acids in aqueous media and water, and studies concerning the reaction mechanism. Excellent enan-tioselectivities (ee up to >99%) were achieved in several cases. As an example of the anh -induction, the (E)-enamine arising from cyclohexanone and the acyclic amino acid could display a proton transfer from the carboxylic acid function to the alkoxide, giving a six-membered chair-like conformation. The favoured approach of the aldehyde would then lead to an anfi-isomer. 

Study of structure-activity relationships in nucleophilic vinylic substitution reactions (S nV) that proceed by the addition-elimination mechanism has been furthered by the study of acid-catalysed breakdown of alkoxide and thiolate ion adducts of benzylidene Meldrum s acid (36a), methoxybenzylidene Meldrum s acid (36b), and thiomethoxybenzylidene Meldrum s acid (36c). Catalysis of alkoxide or thiolate expulsion is in competition with protonation of the a-carbon or one of the carbonyl oxygens to form an enolate. The positive Ag values for H+-catalysed RO and RS departure imply an imbalanced transition state in which proton transfer leads C-O or C-S bond cleavage. The pA values of the various adducts are much lower than for Meldrum s acid, in view of the stabilizing influence of OR, SR, and OMe groups on the carbanion. 

Buxeraud, J., AbsU, A.C., Claude, J. et al. (1985) Antithyroid agents structure-activity relationship. II. Interpretation of the mechanism of action of synthetic antithyroid drugs by formation of charge-transfer complexes. Ear. J. Med. Chem., 20, 43-50. 

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