Synthesis of the 2-methylene analogue of the HRV 3C protease inhibitor thysanone (2-carbathysanone)
作者:Katrin Schünemann、Daniel P. Furkert、Eun Cho Choi、Stephen Connelly、John D. Fraser、Jonathan Sperry、Margaret A. Brimble
DOI:10.1039/c3ob41951g
日期:——
encoded 3C protease that represents an attractive target for the development of therapeutics to treat the common cold. Herein we report the synthesis and biological evaluation of the 2-methylene analogue of the HRV 3C protease inhibitor (−)-thysanone (1) namely 2-carbathysanone (2), in an attempt to decipher the structural features in the natural product that are responsible for the 3C protease activity
该人鼻病毒(HRV)是普通感冒,为此,只有对症治疗可用的主要发病原因。HRV的成熟和复制完全取决于病毒编码的3C蛋白酶的活性,而3C蛋白酶代表了开发感冒药的有吸引力的靶标。本文中,我们报告了HRV 3C蛋白酶抑制剂(-)-胸苷(1)的2-亚甲基类似物,即2-carbathysanone(2)的合成和生物学评估,以试图破译天然产物中的结构特征。负责3C蛋白酶的活性。2- Carbathysanone(2)(以及相关类似物(±) -顺式- 23,(±) -顺式- 30,(±) - 31)没有抑制HRV 3C蛋白酶,这表明存在于(内半缩醛的功能- ) - thysanone(1)是用于抑制所需的关键结构特征。