Target synthesis of bioactive thioglycolurils, based on QSAR predictions

Synthesis of N-{5-Oxo-2-thioxo(2,5-dithioxo)hexahydroimidazo-[4,5-d]imidazol-1(2H)-yl}formamides

“…However, they have already been recognized as substrates for the template-directed crossed-Claisen condensation, 6 organocatalysts for N-Boc protection of amines 7 or α-monobromination of 1,3-dicarbonyl compounds, 8 and as building blocks for the synthesis of semithiobambusurils. 9 Some monothio analogues of glycolurils demonstrate sedative, 10 anxiolytic, 11 and cytotoxic 12 activities. While glycolurils are easily accessible compounds, their thio analogues represent a yet unfulfilled synthetic challenge.…”

“…13 One of the approaches to the synthesis of mono-and dithio analogues of glycolurils is the triazine ring-contraction reaction of 5,7-dialkyl-3-thioxoperhydroimidazo [4,5e]-1,2,4-triazin-6-ones(thiones) 1 with (hetero)aromatic aldehydes in acid medium (HCl) or with nitrous acid. 10,12,14 In general, triazine ring contraction to the imidazolidine ring takes place upon treatment of the corresponding 1,2,4-triazine derivatives with reagents such as sodium dithionite or zinc in acetic acid, 15 benzaldehyde derivatives in acidic medium, 12,14a,16 hydroxylamine-O-sulfonic acid, 17 mercuric(II) oxide, 18 or organolithium reagents. 19 There are a few examples of 1,2,4-triazine ring contraction in the reaction with hydrochloric, acetic, or formic acids.…”

Synthesis of New Substituted Thioglycolurils via a Tandem Hydrazone Formation‐ Ring Contraction Reaction

“…A variety of glycolurils show sedative, anxiolytic, nootropic, neuroprotective effects and induce the liver cytochrome p‐450‐dependent monooxygenase system . Indeed, some of 1,3‐dialkyl‐4‐(benzylideneamino)‐5‐thioxohexahydroimidazo[4,5‐ d ]imidazole‐2(1 H )‐ones possess sedative activity .…”

Synthesis and Structure of 1-Substituted Semithioglycolurils

“…2,6 More and more research has focused on semithioglycolurils I-IX (Figure 1), 2, including compounds I, II, V, VII, and VIII that were synthesized in our laboratory. 6,[12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] Although a wide range of trisubstituted semithioglycolurils I and II have been reported, they are still actively investigated, as some of them have antifungal and cytotoxic activities. 12,13 Other compounds III-IX are represented by several examples and used as scaffolds in the synthesis of semithiobambusurils (III and VII), 11,27 in Claisen condensation matrices (IV), 10 and in the synthesis of tri-, tetra-, and polycyclic systems (V) [28][29][30][31] and iminoglycolurils (V, VII, VIII).…”