Synthesis and in vitro protozoocidal activity of diazabicyclic benzotropolone derivatives

Synthesis and In Vitro Protozoocidal Evaluation of Novel Diazabicyclic Tropolone Derivatives

“…Activities against this parasite ranged from more than one order of magnitude higher than the control for compound 5f, to nearly two orders of magnitude higher in the case of diazabicycles 4d and 4e. As it was observed for our previous series of benzotropolone-based hydrazines [9], the data presented in Table 1 also show that the activity of the compounds correlates with the lipophilicity of their ether and carbamate groups. This finding further emphasizes the importance of membrane permeability in the activity of this class of compounds [7 -9].…”

“…Following the preparation of ethers 2a -2i, the final products were obtained using hetero Diels -Alder reaction conditions described by us in earlier reports [8,9]. Thus, treatment of the tropanes with a two-fold molar excess of the electron-deficient diazo-containing dienophiles dimethyl, diethyl, and diisopropylazodicarboxylate (DMAD, DEAD, and DIAD, respectively) in refluxing toluene led cleanly to the desired diazabicyles.…”

“…Thus, treatment of the tropanes with a two-fold molar excess of the electron-deficient diazo-containing dienophiles dimethyl, diethyl, and diisopropylazodicarboxylate (DMAD, DEAD, and DIAD, respectively) in refluxing toluene led cleanly to the desired diazabicyles. Once again, the dienophiles employed in the cycloadditions were selected so as to yield compounds with substitution patterns analogous to those of the already studied benzotropolone-based series [8,9]. As we have observed in the past, the success of the reactions could be easily established by 1 H-NMR [7 -9].…”

Use of Photochemical Transformations as a Route to Novel Molecular Scaffolds

“…The substrates used for this purpose have been investigated by our groups as potential antiparasitic agents. 1,2 The compounds are a series of Diels-Alder adducts formed between benzotropolones or tropolones with suitable dienophiles, and which bear a common β,γ-unsaturated ketone chromophore. As detailed herein, the phototransformations are initiated by the formation of stable allyl or allyl/aroyl radicals.…”

Mechanistic Studies of the Formation of Functionalized Cyclopropanes through Photoisomerization of Tropolone Diels-Alder Adducts

“…[1][2][3][4][5] Some of these compounds display promising in vitro activities against Trypanosoma cruzi and Leishmania donovani. To expand the structural diversity of our libraries, and based on results obtained for similar β,γ-unsaturated ketone chromophores, 7,8 we studied the photoisomerization these alkyltropolone derivatives.…”