CICS-UBI - Health Sciences Research Center, University of Beira Interior, Av. Infante D. Henrique, 6200-506, Covilhã, Portugal.
Department of Chemistry, University of Beira Interior, Rua Marquês d'Ávila e Bolama, 6201-001, Covilhã, Portugal.
Mol Divers. 2020 Feb;24(1):155-166. doi: 10.1007/s11030-019-09937-4. Epub 2019 Mar 14.
Benzisoxazoles represent an important pharmacophore in medicinal chemistry. Recently, an unexpected formation of symmetric 3-substituted 2,1-benzisoxazoles through reduction of 5-(2-nitrobenzylidene)barbiturates has been described. This reductive intramolecular heterocyclization probably involves a nitroso intermediary. To improve the previous reaction conditions, the nature of the reducing agent and additives, reaction time and solvents were evaluated. By applying the optimized conditions, several symmetric and unsymmetric barbiturates C5-coupled with 2,1-benzisoxazoles were prepared with an yield of 52-87%. From this set, seven compounds were novel and the unsymmetric nature of the (thio)barbituric acid moiety was explored. For that, the total synthesis, starting from the respective urea or thiourea, was successfully performed, and 11 thiobarbiturates, benzylidene barbiturate and thiobarbiturate precursors are described.
苯并恶唑是药物化学中一个重要的药效团。最近，通过还原 5-(2-亚硝基苯甲叉基)巴比妥酸，出乎意料地形成了对称的 3-取代 2,1-苯并恶唑。这种还原的分子内环化可能涉及亚硝基中间体。为了改进以前的反应条件，评估了还原剂和添加剂的性质、反应时间和溶剂。通过应用优化的条件，用 52-87%的收率制备了几个对称和不对称的 C5-与 2,1-苯并恶唑偶联的巴比妥酸。在这一组中，有七个化合物是新的，并且探索了（硫）巴比妥酸部分的不对称性质。为此，成功地进行了从各自的脲或硫脲开始的全合成，并描述了 11 个硫巴比妥酸、亚苄基巴比妥酸和硫巴比妥酸前体。
