Synthesis, Structures and Antifungal Activity of Selenoglycolurils

Abstract

A synthetic method for the preparation of selenoglycolurils is reported. Target compounds were obtained by two‐stage transformation of unsubstituted, 1‐substituted and 1,3‐disubstituted thioglycolurils by S‐methylation with MeI to the corresponding isothiouronium salts (Step 1) followed by selenation with NaHSe generated in situ from grey Se and NaBH4 (Step 2). Selenoglycolurils possessed potent antifungal activity against Candida albicans and Cryptococcus neoformans (MIC 0.25–0.125 μg/mL) with no discernable toxicity against mamallian cells, supporting the unique role of organoselenium compounds as novel antifungal agents.

Synthesis of the First Representatives of new 3,3a‐Dihydro‐1H‐Imidazo[4′,5′:4,5]Imidazo[2,1‐b]thia(selena)zole Heterocyclic Systems with Fungicidal Activity

“…The completeness of the transformations was controlled by TLC using the same eluent by the disappearance of spots of the starting compounds 4 b , c , 5 a , b and 6 a – c (R f 0.23 for 4 b , 0.35 for 4 c , 0.29 for 5 a , 0.38 for 5 b , 0.11 for 6 a , 0.23 for 6 b , 0.31 for 6 c ) and with 1 H NMR monitoring of dried reaction mixture aliquots for compounds 4 d , 6 d by the disappearance of CH−CH proton signals (s, 5.42 ppm and 5.40 ppm, respectively) [22,23] . It was found that the conditions ( i ) are applicable for the preparation of imidazoimidazothiazole 1 b (yield after isolation 89 %) and imidazoimidazoselenazoles 3 a , b (yields 59 % and 56 %, respectively).…”

“…Preparation of selenoglycolurils 6 a – d was carried out in 2 stages: first, isothiouronium salts were obtained through S‐methylation of semithioglycolurils 4 a – d with MeI. At the second stage, nucleophilic substitution of the S−Me group with a selenium atom was carried out by the reaction of isothiouronium salts with generated in situ NaHSe [23] …”

“…At the second stage, nucleophilic substitution of the SÀ Me group with a selenium atom was carried out by the reaction of isothiouronium salts with generated in situ NaHSe. [23]…”

“…The developed conditions (i) were used in regioselective reactions of DEAD with semithioglycolurils [22,23] It was found that the conditions (i) are applicable for the preparation of imidazoimidazothiazole 1 b (yield after isolation 89 %) and imidazoimidazoselenazoles To synthesize imidazoimidazoselenazole 3 d, a further increase in temperature was necessary, so the initial model conditions were used. (Scheme 2, conditions (iv), yield 65 %).…”