Synthesis and structural characterization of N-substituted azoles with potential pharmacological
                                            activities

                                         Shivaji S. Kadam

   The main goal of our study is to synthesize and structurally characterize the N-substituted
azoles. They are indispensable components of many pharmaceuticals and therapeutic drugs. This study
comprises of two main projects: isoquninoline alkaloids and pyrazolopyrazoles.

   The basic skeletons of quaternary protoberberine alkaloids and quaternary benzophenanthridine
alkaloids contain iminium bonds (C=N^+), which are rather sensitivity to the nucleophilic attack
resulting in the formation on covalent adducts - 8-substituted-7,8-dihydroprotoberberines and
6-substituted-5,6-dihydrobenzophenanthridines, respectively. All new compounds were characterized
by using mass spectrometry, NMR spectroscopy, and some of them also by X-ray diffraction. We have
found some interesting trends in the experimental NMR chemical shifts, which were rationalized by
density-functional calculations.

 Scheme 1. Nucleophilic addition of azoles to a quaternary protoberberine skeleton.

  Substituted purines and purine analogues represent an important group of heterocyclic compounds.
Generally, these compounds can exist in a number of tautomeric forms, which are relevant to any
investigation of their binding modes with biological targets. We have synthesized a series of
variously substituted analogs derived from pyrazolo[4,3-c]pyrazole and investigated their
tautomeric equilibria using model systems of N-methylated pyrazolo[4,3-c]pyrazoles.


Scheme 2. Three tautomeric forms (N1H/N4H, N2H/N4H, and N1H/N5H) of pyrazolo[4,3-c]pyrazoles.