5 Amidines and Guanidines in Medicinal Chemistry

Metal-promoted synthesis of amidines containing the model nucleobases 1-methylcytosine and 9-methyladenine

“…The single crystal X-ray analysis of the cytosine derivative cis-[(PPh 3 ) 2 PtNH C(Ph){1-MeCy(-2H)}]NO 3 confirms the coordination features of the anionic ligand previously described for the PMePh 2 analogue 10 and allows the examination of the structural differences between the free and the coordinated benzimidamides. Finally, the reactivity of Me 3 C-CN and Ph 2 (H)C-CN has been explored, showing that the insertion of these hindered nitriles into the platinum-nucleobase bond is incomplete in the case of 9-MeAd, while the amidine complexes cis-[(PPh 3 ) 2 PtNH C(R){1-MeCy(-2H)}]NO 3 [R = Me 3 C and Ph 2 (H)C] can been isolated in high yield.…”

“…These neutral species, insoluble in H 2 (Fig. S2, ESI †) of 5b indicate that both the NH signals at d 11.56 and 7.14 ppm correlate with the same 15 N nucleus (at d -266 ppm), in agreement with the presence of two hydrogen atoms bound to the same nitrogen.…”

“…8(3) • in 3b and 5b, respectively, than the values observed in the complexes. The phenyl ring is tilted by 29.86(5) and 7.1 (2) • in amidine molecules 3b and 5b, respectively. A more interesting observation is that the dihedral angle formed by the cytosine ring with the C7/C3/N2/N4 moiety, of ca.…”

“…The stabilization of the imino tautomer through metal coordination has been also investigated by reacting these amidines with the complex cis-L 2 Pt(ONO 2 ) 2 (L = PPh 3 ) containing the labile nitrato ligands. 12 The adducts, tentatively formulated as cis-[L 2 PtNH C(Ph){nucleobase(-H)}](NO 3 ) 2 , quantitatively convert into cis-[L 2 PtNH C(Ph){nucleobase(-2H)}]NO 3 , by addition of a "proton sponge".…”

“…Finally, the reactivity of Me 3 C-CN and Ph 2 (H)C-CN has been explored, showing that the insertion of these hindered nitriles into the platinum-nucleobase bond is incomplete in the case of 9-MeAd, while the amidine complexes cis-[(PPh 3 ) 2 PtNH C(R){1-MeCy(-2H)}]NO 3 [R = Me 3 C and Ph 2 (H)C] can been isolated in high yield. They are structurally analogous to the acetonitrile and benzonitrile derivatives, suggesting that the use of appropriate nitriles can lead to a variety of metallacycle complexes from which new amidines can be prepared.…”