Synthesis and In Vitro Protozoocidal Evaluation of Novel Diazabicyclic Tropolone Derivatives

Abstract

The synthesis and in vitro antiparasitic activity of twenty-seven novel diazabicycles based on tropolone ethers is presented. The compounds can be readily prepared by means of a high-yielding hetero Diels-Alder reaction using simple and readily available starting materials. Several of the new diazabicycles have in vitro activities against Trypanosoma cruzi, Leishmania donovani, Trypanosoma brucei rhodesiense, and chloroquine-resistant Plasmodium falciparum that are comparable or superior to those of currently employed protozoocidal agents.

Photochemical Preparation of Novel Tetracyclic Indenoquinolines from Benzotropolone Derivatives

“…As we recently reported, Diels-Alder adducts formed between benzotropolones and nitrosobenzene can be photoisomerized in fair yields to novel tetraindenoquinolines. 3 Based on these results, and on previous work carried out by our groups, 4 we were able to increase the diversity of the compounds in the series. Starting form trimethylpurporogallin, a series of aliphatic and aromatic ethers were prepared using standard Williamson conditions.…”

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.…”

Synthesis and antitumoral evaluation of natural product‐like compounds based on tropolone and benzotropolone derivatives

“…[8][9][10][11] Based on a simple diversity-oriented synthetic (DOS) strategy that employs tropolones and benzotropolones as precursors and combines Diels-Alder reactions and photochemical transformations as key steps, our group has developed highly functionalized NPLCs families with polycyclic motifs, including homobarrelenones, indenoquinolines, indenopyridazines, dihydrofluorenones, diazabicyclo [4.1.0]heptenes, and bicyclo[4.1.0]heptenes (norcaranes). [12][13][14][15][16][17][18][19] Several of the compounds prepared using diazo or nitroso dienophiles in the [4+2] cycloaddition step displayed good antiparasitic and antitumoral activity, [12][13][14]18] indicating that the approach is a valuable tool for the identification of structurally novel leads with diverse biological activity. In addition, a number of recent reports describe a number of tropolone and benzotropolone derivatives with activities that rival those of cisplatin and colchicine, [20][21][22][23] further showcasing the potential of these aromatic dienes as scaffolds in the design of novel antineoplastic agents.…”