Rocio Gamez-Montano
University of Guanajuato, Mexico
Title: Synthesis of methane-linked bis-heterocycles containing the 1,5-disubstituted-tetrazole moiety via Ugi-azide based methodologies
Biography
Biography: Rocio Gamez-Montano
Abstract
Bis-heterocycles are structurally complex compounds having two linked, fused, merged or bound heterocyclic frameworks,1 which have attracted much attention of synthetic community due to their potential applications in agrochemistry, optics, material science, and medicinal chemistry.2 Moreover, 1,5-disubstituted-tetrazoles (1,5-DS-T’s) are known as resistant bioisosters of the cis-amide bond of peptides,3 which are present in numerous valuable drugs like the 3rd generation cephalosporin antibiotic Latamoxeb.4 Besides, 1,5-DS-T’s are suitable precursors of a plethora of MOF´s and chelating agents.5 Thus, according to our ongoing program to develop short and versatile Ugi-azide based methodologies toward a variety of methane-linked bis-heterocycles containing the 1,5-DS-T moiety, we herein show our most recent published results.
In 2013, we described the synthesis of azepino[4,5-b]indol-4-one-1,5-1H-tetrazoles in two steps: i) one pot (Ugi-azide/N-acylation/SN2), and ii) free radical mediated cyclization, as well as in silico studies as 5-Ht6R ligands using docking techniques (Figure 1a).6 In 2014, we reported the synthesis of 2,3,4,9-tetrahydro-b-carboline-1,5-1H-tetrazoles by a one pot Ugi-azide / Pictet-Spengler process (Figure 1b).7 In 2014, we reported the synthesis of chromen-4-ones-1,5-1H-tetrazoles via the Ugi-azide reaction and in vitro studies of antiparasitic properties against E. histolytica, G. lamblia, and T. vaginalis.8 Then, in 2015 we extended this work synthesizing some fluorinated analogs, which together with the previously synthesized bis-heterocycles were assayed in vitro against P. aeruginosa, S. aureus, S. schenckii, C. albicans, and C. tropicalis (Figure 1c).9 Finally, just recently in 2016, we reported the synthesis of novel 3-tetrazolyl-tetrazolo[1,5-a]quinolines via a novel one pot Ugi-azide / SNAr / ring-chain azido-tautomerization process (Figure 1d).10 As seen, the Ugi-azide reaction or its combination with further cyclization processes allows the rapid synthesis of a variety of methane-linked bis-heterocycles with potential application mainly in medicinal chemistry because 1,5-DS-T framework has been suitably combined with other heterocyclic systems, which are present in numerous bioactive products, even in drugs.
Figure 1