Piperidinols That Show Anti-Tubercular Activity as Inhibitors of Arylamine N-Acetyltransferase: An Essential Enzyme for Mycobacterial Survival Inside Macrophages
Figure 6
The chemical transformation of 1 to the corresponding phenyl vinyl ketone (PVK) and the subsequent modification of a thiol containing residue by the PVK.
(A) A proposed pathway of the formation of bis-Mannich bases from the rigid cyclic piperidinol. The bis-Mannich base can undergo a β-elimination of the amino group forming a reactive phenyl vinyl ketone (PVK). (B) The PVK reaction with thiols resulted in the addition of a 3-phenyl-3-oxopropyl moiety (POP) (when R1 is H) or a 3-(4-chlorophenyl)-3-oxopropyl moiety (when R1 is Cl). The expected Δm values of the added fragments are +132.07 Da and +166 Da, respectively. The shaded areas highlight the Michael acceptor moiety. Since the PVK binding species is transient, the second order rate constant cannot be determined without major assumptions being made.