Target-Guided Synthesis or Freeze-Frame Click Chemistry

4 Target-Guided Synthesis or Freeze-Frame Click Chemistry 

This reaction proceeded at the AChE active site with nearly complete syn- or 1,5-selectivity, controlled by the topology of the narrow gorge. Strikingly uniform sy -selectivity was obtained for enzyme-produced triazoles, independently of the linker length and stereochemistry of the acetylene reagent. 

Generally, sy -compounds proved highly effective non-covalent inhibitors of AChE, in sharp contrast to their anti-isomers. The difference in kinetic parameters for the representative couple of isomers syn-4lanti-4, as determined for mouse AChE, is impressive (Table 15.1) [28]. 

Reagents and conditions /. AChE (mouse), active-site concn. 1 mM, r.t. 

Solid phase 7 represents a regenerative Michael receptor (REM), since on addition of phenylpiperazines I, a library of solid-phase derivatives II is formed. On benzylation by benzylbromides III, quartemary amonium salts IV are formed. 

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