Lish Matthew S, Milanes Jillian E, Sanders Kyana M, Guzei Ilia A, Morris James C, Golden Jennifer E
Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, 53706, United States.
Eukaryotic Pathogens Innovation Center, Department of Genetics and Biochemistry, Clemson University, Clemson, South Carolina, 29634, United States.
Adv Synth Catal. 2023 Dec 19;365(24):4567-4575. doi: 10.1002/adsc.202300994. Epub 2023 Nov 20.
A three-step synthesis of anti-amoebic, ring-fused mackinazolinones has been developed. A Mannich-type reaction between quinazolin-4-ones and -Cbz propanal in the presence of AgOTf afforded quinazolinones (19-94% isolated yield) bearing a newly formed heterocycle with an alkylamine appendage that, upon -Cbz deprotection and basification, triggered a domino rearrangement to afford 45 separable, ring-fused products. Several compounds inhibited growth of parasites that can cause a lethal human brain infection. Thus, the methodology provides immediate access to a promising anti-amoebic scaffold.
已开发出一种三步合成抗阿米巴环稠合麦基那唑啉酮的方法。喹唑啉-4-酮与-Cbz丙醛在AgOTf存在下发生曼尼希型反应，得到带有新形成的带有烷基胺附属物的杂环的喹唑啉酮（分离产率为19-94%），该附属物在-Cbz脱保护和碱化后引发多米诺重排，得到45种可分离的环稠合产物。几种化合物抑制了可导致致命人脑感染的寄生虫的生长。因此，该方法可直接获得一种有前景的抗阿米巴骨架。
