无痕固相α-羟基托酚酮合成。
Traceless Solid-Phase α-Hydroxytropolone Synthesis.
作者信息
D'Erasmo Michael P, Masaoka Takashi, Wilson Jennifer A, Hunte Errol M, Beutler John A, Le Grice Stuart F J, Murelli Ryan P
机构信息
Department of Chemistry, Brooklyn College, The City University of New York, Brooklyn, New York, USA; PhD Program in Chemistry, The Graduate Center of The City University of New York, New York, NY, USA.
Basic Research Laboratory, National Cancer Institute, Frederick, MD, USA.
出版信息
Medchemcomm. 2016 Sep 1;7(9):1789-1792. doi: 10.1039/C6MD00237D. Epub 2016 Jul 7.
Abstract
α-Hydroxytropolones are established inhibitors of several therapeutically relevant binuclear metalloenzymes, and thus lead drug targets for various human diseases. We have leveraged a recently-disclosed three-component oxidopyrylium cycloaddition in the first solid-phase synthesis of α-hydroxytropolones. We also showed that, while minor impurities exist after cleavage and aqueous wash, the semi-crude products display activity in HIV RT-associated RNaseH enzymatic and cell-based assays consistent with pure molecules made in solution phase. These proof-of-principle studies demonstrate the feasibility of solid-phase α-hydroxytropolone synthesis and its potential to serve as a powerful platform for α-hydroxytropolone-based drug discovery and development.
摘要
α-羟基托酚酮是几种具有治疗意义的双核金属酶的既定抑制剂，因此是多种人类疾病的潜在药物靶点。我们利用最近披露的三组分氧化吡啶环加成反应首次实现了α-羟基托酚酮的固相合成。我们还表明，虽然在裂解和水洗后存在少量杂质，但半粗产物在HIV逆转录酶相关的核糖核酸酶H酶促和细胞实验中表现出与溶液相合成的纯分子一致的活性。这些原理验证研究证明了固相合成α-羟基托酚酮的可行性及其作为基于α-羟基托酚酮的药物发现和开发强大平台的潜力。
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Synthetic α-Hydroxytropolones Inhibit Replication of Wild-Type and Acyclovir-Resistant Herpes Simplex Viruses.合成α-羟基环庚三烯酚酮抑制野生型和阿昔洛韦耐药型单纯疱疹病毒的复制。
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