Piperidine from arginine

Heterocyclic enamines A -pyrroline and A -piperideine are the precursors of compounds containing the pyrrolidine or piperidine rings in the molecule. Such compounds and their N-methylated analogs are believed to originate from arginine and lysine (291) by metabolic conversion. Under cellular conditions the proper reaction with an active methylene compound proceeds via an aldehyde ammonia, which is in equilibrium with other possible tautomeric forms. It is necessary to admit the involvement of the corresponding a-ketoacid (12,292) instead of an enamine. The a-ketoacid constitutes an intermediate state in the degradation of an amino acid to an aldehyde. a-Ketoacids or suitably substituted aromatic compounds may function as components in active methylene reactions (Scheme 17). 

First, the needle itself, amidino-piperidine, has Kj for thrombin of 150 pM and for trypsin 360 pM and thus is 2.4 x selective for thrombin. This contrasts with the classical needle benzamidine, which has fQ for thrombin of 300 pM and 31 pM for trypsin and thus is 10 X selective for trypsin. This is perhaps unexpected, as it could be argued that benzamidine, being planar, is a much better analogue of the substrate arginine guanidinium group. The width of the recognition pocket (measured from... 

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