Synthesis, Structure, and Antiradical Activity of New Methano[1,3]Thiazolo[2,3-d][1,3,5]Benzoxa-Diazocine Derivatives

Abstract

There has been a recent significant increase in the number of publications devoted to the chemistry of 3,4-dihydropyrimidin-2-ones(thiones) 1, 2, obtained by three-component condensation in Biginelli reaction. The reasons for this include not only the preparative accessibility of 3,4-dihydropyrimidin-2-ones(thiones) 1, 2, but also the broad spectrum of pharmacological activity characteristic of these compounds, including analgesic, antibacterial, antihypertensive, and other properties [1-3], which motivate the further study of such compounds.The mechanism of Biginelli reaction is now well understood [4], many derivatives of 3,4-dihydropyrimidin-2-ones 1 and 3,4-dihydropyrimidine-2-thiones 2 with various functional substituents have been synthesized, many preparative methods have been developed and patented, including solvent-free microwaveassisted procedures, and highly effective catalysts have been discovered, leading to significant increase of yields and shorter reaction times [5][6][7][8][9][10][11][12][13].The range of applications for 3,4-dihydropyrimidine-2-thiones was also extended when 4-(3-hydroxyphenyl)pyrimidine-2-thione derivative 3 was synthesized, which is known as monastrol, a compound characterized by a completely new mechanism of anticancer activity through specific influence on cell division (mitosis) [14]. It is not surprising that synthesis of new derivatives of monastrol 3 has been recently performed by the research groups of Bose [15] and Dondoni [16].

Synthesis, Structure, and Some Transformations of Novel 1,5‐methanonaphtho[1,2‐g][1,3,5]oxadiazocine Derivatives

“…The bond lengths in the molecules of 6 and 8a (except for the thiazole ring) are close to those in the analogous compounds: 13‐acetyl‐9‐bromo‐5‐methyl‐5,11‐dihydro‐5,11‐methano[1,3]thiazolo[2,3‐d][1,3,5]benzoxadiazocin‐1(2 H )‐one and (2Z)‐2‐(2‐furylmethylene)‐11 H ‐5,11,5‐pentane[1,1,5]triyl[1,3]thiazolo[2,3‐d][1,3,5]benzoxadiazocin‐1‐one accordingly. The bond lengths in the benzylidene‐thiazole fragment of compound 8a are close to those in 2‐((1,3‐benzodioxol‐5‐yl)methylene)‐6,7‐dihydro‐5 H ‐thiazolo[3,2‐a]pyrimidin‐3‐one .…”

“…Similarly to 2,6‐methano[1,3,5]benzoxadiazocine derivatives , compounds 4 and 5 were converted to the previously unknown tetracyclic 5 H ,13 H ‐5,13‐methanonaphtho[1,2‐g]thiazolo[2,3‐d][1,3,5]oxadiazocin‐1(2 H )‐ones 6 and 7 when boiled in toluene in the presence of a small excess of α‐chloroacetamide and triethylamine (Scheme ). In contrast with methanobenzo[g]thiazolo[2,3‐d][1,3,5]oxadiazocines , condensation of compounds 6 and 7 with aromatic aldehydes in the presence of catalytic amounts of formic acid in 2‐propanol took place for 15–20 h to give the corresponding ylidene derivatives 8a – c and 9a – c .…”

“…Of particular interest was to study the spatial structure of the first representatives of the tetracyclic derivatives 5 H ,13 H ‐5,13‐methanonaphtho[1,2‐g]thiazolo[2,3‐d][1,3,5]oxadiazocin‐1(2 H )‐one in comparison with the previously described derivatives . In this regard, we performed single‐crystal X‐ray diffraction study of compounds 6 and 8a (Figs.…”

“…Recently, we reported that 2H‐2,6‐methanobenzo [g][1,3,5]oxadiazocines 1b , synthesized by the Biginelli reaction, have antiradical activity . Similarly to 3,4‐dihydropyrimidin‐2 (1H)‐one , they readily react with the amide of monochloroacetic acid to form tricyclic methanobenzo[g]thiazolo [2,3‐d] [1,3,5]oxadiazocine, which can be used to obtain condensation derivatives with carbonyl compounds involving a methylene fragment of the fused thiazole ring .…”

Synthesis, Structure and Molecular Docking of New 4,5-Dihydrothiazole Derivatives Based on 3,5-Dimethylpyrazole and Cytisine and Salsoline Alkaloids

“…Most thiourea and thioureide derivatives have not only valuable pharmacological properties and are used as antiepileptic drugs [ 51 ], antidiabetic [ 52 ], anti-cancer [ 53 ], anti-tuberculosis [ 54 ] and other therapeutically active substances [ 55 ], but they are also initial synthons in the synthesis of many sulfur-containing heterocycles [ 56 , 57 , 58 , 59 , 60 ].…”