3,7 - 二羟基卓酚酮的合成与生物学评估
Synthesis and biological assessment of 3,7-dihydroxytropolones.
作者信息
Hirsch D R, Schiavone D V, Berkowitz A J, Morrison L A, Masaoka T, Wilson J A, Lomonosova E, Zhao H, Patel B S, Datla S H, Hoft S G, Majidi S J, Pal R K, Gallicchio E, Tang L, Tavis J E, Le Grice S F J, Beutler J A, Murelli R P
机构信息
Department of Chemistry, Brooklyn College, The City University of New York, Brooklyn, New York, 11210, USA.
出版信息
Org Biomol Chem. 2017 Dec 19;16(1):62-69. doi: 10.1039/c7ob02453c.
Abstract
3,7-Dihydroxytropolones (3,7-dHTs) are highly oxygenated troponoids that have been identified as lead compounds for several human diseases. To date, structure-function studies on these molecules have been limited due to a scarcity of synthetic methods for their preparation. New synthetic strategies towards structurally novel 3,7-dHTs would be valuable in further studying their therapeutic potential. Here we describe the successful adaptation of a [5 + 2] oxidopyrilium cycloaddition/ring-opening for 3,7-dHT synthesis, which we apply in the synthesis of a plausible biosynthetic intermediate to the natural products puberulic and puberulonic acid. We have also tested these new compounds in several biological assays related to human immunodeficiency virus (HIV), hepatitis B virus (HBV) and herpes simplex virus (HSV) in order to gain insight into structure-functional analysis related to antiviral troponoid development.
摘要
3,7-二羟基环庚三烯酚酮（3,7-dHTs）是高度氧化的环庚三烯酚酮类化合物，已被确定为多种人类疾病的先导化合物。迄今为止，由于缺乏制备这些分子的合成方法，对其结构-功能的研究受到限制。开发结构新颖的3,7-dHTs的新合成策略对于进一步研究其治疗潜力具有重要价值。在此，我们描述了一种成功应用于3,7-dHT合成的[5 + 2]氧化吡啶环加成/开环反应，该反应应用于天然产物柔毛酸和柔毛酮酸可能的生物合成中间体的合成。我们还在与人类免疫缺陷病毒（HIV）、乙型肝炎病毒（HBV）和单纯疱疹病毒（HSV）相关的几种生物学试验中测试了这些新化合物，以便深入了解与抗病毒环庚三烯酚酮开发相关的结构-功能分析。
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