Lystsova Ekaterina A, Novikov Alexander S, Dmitriev Maksim V, Maslivets Andrey N, Khramtsova Ekaterina E
Department of Organic Chemistry, Perm State University, ul. Bukireva, 15, 614990 Perm, Russia.
Institute of Chemistry, Saint Petersburg State University, Universitetskaya nab. 7/9, 199034 St. Petersburg, Russia.
Molecules. 2023 Jul 18;28(14):5495. doi: 10.3390/molecules28145495.
Acyl(imidoyl)ketenes are highly reactive heterocumulenes that enable diversity-oriented synthesis of various drug-like heterocycles. Such ketenes, bearing heterocyclic substituents, afford angularly fused pyridin-2(1)-ones in their [4+2]-cyclodimerization reactions. We have utilized this property for the development of a new synthetic approach to pharmaceutically interesting pyrido[2,1-][1,3]benzothiazol-1-ones via the [4+2]-cyclodimerization of acyl(1,3-benzothiazol-2-yl)ketenes generated in situ. The thermal behaviors of 3-aroylpyrrolo[2,1-][1,4]benzothiazine-1,2,4-triones and 3-benzoylpyrrolo[2,1-][1,3]benzothiazole-1,2-dione (two new types of []-fused 1-pyrrole-2,3-diones reported by us recently) have been studied by thermal analysis and HPLC to elucidate their capability to be a source of acyl(1,3-benzothiazol-2-yl)ketenes. As a result, we have found that only 3-aroylpyrrolo[2,1-][1,4]benzothiazine-1,2,4-triones are suitable for this. The experimental results are supplemented with computational studies that demonstrate that thermolysis of 3-aroylpyrrolo[2,1-][1,4]benzothiazine-1,2,4-triones proceeds through an unprecedented cascade of two thermal decarbonylations. Based on these studies, we discovered a novel mode of thermal transformation of []-fused 1-pyrrole-2,3-diones and developed a new pot, atom, and step economic synthetic approach to pyrido[2,1-][1,3]benzothiazol-1-ones. The synthesized drug-like pyrido[2,1-b][1,3]benzothiazol-1-ones are of interest to pharmaceutics, since their close analogs show significant antiviral activity.
酰基（亚氨基）烯酮是高反应性的杂累积烯烃，可用于多种类药物杂环的多样性导向合成。这类带有杂环取代基的烯酮在其[4+2]环二聚反应中可生成角稠合的吡啶-2(1)-酮。我们利用这一性质，通过原位生成的酰基（1,3-苯并噻唑-2-基）烯酮的[4+2]环二聚反应，开发了一种合成具有药学意义的吡啶并[2,1-][1,3]苯并噻唑-1-酮的新方法。我们通过热分析和高效液相色谱研究了3-芳酰基吡咯并[2,1-][1,4]苯并噻嗪-1,2,4-三酮和3-苯甲酰基吡咯并[2,1-][1,3]苯并噻唑-1,2-二酮（我们最近报道的两种新型稠合1-吡咯-2,3-二酮）的热行为，以阐明它们作为酰基（1,3-苯并噻唑-2-基）烯酮来源的能力。结果发现，只有3-芳酰基吡咯并[2,1-][1,4]苯并噻嗪-1,2,4-三酮适用于此。实验结果辅以计算研究，结果表明3-芳酰基吡咯并[2,1-][1,4]苯并噻嗪-1,2,4-三酮的热解通过前所未有的两步热脱羰基级联反应进行。基于这些研究，我们发现了稠合1-吡咯-2,3-二酮的新型热转化模式，并开发了一种新的一锅法、原子经济性和步骤经济性的合成吡啶并[2,1-][1,3]苯并噻唑-1-酮的方法。合成的类药物吡啶并[2,1-b][1,3]苯并噻唑-1-酮在药学上具有吸引力，因为它们的类似物显示出显著的抗病毒活性。
