Bisubstrate reaction templates

Scheme 12.21 Self-assembling catalysis via a ternary complex involving a bisubstrate reaction template.30...

T.R. Kelly et al. have synthesized bisubstrate reaction templates utilizing the Chichibabin amination reaction during the preparation of one precursor. This reaction template was designed to use hydrogen bonding to bind two substrates simultaneously but transiently, giving rise to a ternary complex, which positions the substrates in an orientation that facilitates their reaction. 

Kelly, T. R., Bridger, G. J., Zhao, C. Bisubstrate reaction templates. Examination of the consequences of identical versus different binding sites. J. Am. Chem. Soc. 1990,112, 8024-8034. 

The most commonly used ADA modules contain the pyrimidine-2,4-dione nucleus. Not surprisingly, N-alkylation of thymine or uracil with an alkyl halide provides a simple, one-step method of functionalizing this module. Other ADA units include simple imides (e.g., 10), heterocycle 13, which was used by Kelly in a bisubstrate reaction template [17], and the anthyridinone or anthyridan units in 15 and 18, respectively. The latter modules are synthesized by double Friedlander condensation of 2,6-diaminopyridine-3,5-dicarboxal-... 

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