作为制备含硝基官能团的含硫五元杂环的可用天然结构单元的丙硫醛 S-氧化物：一种分子中的电子密度拓扑研究。

-Propanethial S-Oxide as an Available Natural Building Block for the Preparation of Nitro-Functionalized, Sulfur-Containing Five-Membered Heterocycles: An MEDT Study.

作者信息

Sadowski Mikołaj, Dresler Ewa, Zawadzińska Karolina, Wróblewska Aneta, Jasiński Radomir

机构信息

Department of Organic Chemistry and Technology, Cracow University of Technology, Warszawska 24, 31-155 Krakow, Poland.

Łukasiewicz Research Network-Institute of Heavy Organic Synthesis "Blachownia", Energetyków 9, 47-225 Kędzierzyn-Koźle, Poland.

出版信息

Molecules. 2024 Oct 15;29(20):4892. doi: 10.3390/molecules29204892.

The regio- and stereoselectivity and the molecular mechanisms of the [3 + 2] cycloaddition reactions between -propanethial S-oxide and selected conjugated nitroalkenes were explored theoretically in the framework of the Molecular Electron Density Theory. It was found that cycloadditions with the participation of nitroethene as well as its methyl- and chloro-substituted analogs can be realized via a single-step mechanism. On the other hand, [3 + 2] cycloaddition reactions between -propanethial S-oxide and 1,1-dinitroethene can proceed according to a stepwise mechanism with a zwitterionic intermediate. Finally, we evaluated the affinity of model reaction products for several target proteins: cytochrome P450 14α-sterol demethylase CYP51 (RSCB Database PDB ID: 1EA1), metalloproteinase gelatinase B (MMP-9; PDB ID: 4XCT), and the inhibitors of cyclooxygenase COX-1 (PDB:3KK6) and COX-2 (PDB:5KIR).

在分子电子密度理论框架下，从理论上探索了β-丙硫醛S-氧化物与选定的共轭硝基烯烃之间[3 + 2]环加成反应的区域选择性、立体选择性及分子机制。研究发现，硝基乙烯及其甲基和氯取代类似物参与的环加成反应可通过单步机制实现。另一方面，β-丙硫醛S-氧化物与1,1-二硝基乙烯之间的[3 + 2]环加成反应可通过具有两性离子中间体的分步机制进行。最后，我们评估了模型反应产物对几种靶蛋白的亲和力：细胞色素P450 14α-甾醇脱甲基酶CYP51（RSCB数据库PDB ID：1EA1）、金属蛋白酶明胶酶B（MMP-9；PDB ID：4XCT）以及环氧合酶COX-1（PDB：3KK6）和COX-2（PDB：5KIR）的抑制剂。