受天然产物启发，在质子溶剂中对邻氨基酚加合物进行反-aza-Michael 反应。
Retro-aza-Michael reaction of an o-aminophenol adduct in protic solvents inspired by natural products.
机构信息
Department of System Chemotherapy and Molecular Sciences, Division of Bioinformatics and Chemical Genomics, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
Department of System Chemotherapy and Molecular Sciences, Division of Bioinformatics and Chemical Genomics, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan; Department of Biotechnology, The University of Tokyo, Tokyo 113-8657, Japan; Collaborative Research Institute for Innovative Microbiology, The University of Tokyo, Tokyo 113-8657, Japan.
出版信息
Bioorg Med Chem. 2021 Apr 1;35:116059. doi: 10.1016/j.bmc.2021.116059. Epub 2021 Feb 13.
α,β-Unsaturated carbonyls are reactive group often found in bioactive small molecules. Their non-specific reaction with biomolecules can be the cause of the low efficacy and unexpected side-effects of the molecule. Accordingly, unprotected α,β-unsaturated carbonyls are not often found in drugs. Here, we report that o-aminophenol is a new masking group of α,β-unsaturated ketone, which is inspired by natural products saccharothriolides. o-Aminophenol adduct of α,β-unsaturated ketone, but not those of α,β-unsaturated amide or ester, undergoes a retro-Michael reaction to yield o-aminophenol and the Michael acceptor. This reaction was observed only in protic solvents, such as MeOH and aqueous MeOH. In contrast, o-anisidine was not eliminated from its Michael adduct. o-Aminophenol may be a promising masking tool of highly-reactive bioactive α,β-unsaturated carbonyl compounds.
α,β-不饱和羰基是生物活性小分子中常见的反应基团。它们与生物分子的非特异性反应可能是导致分子低疗效和意外副作用的原因。因此，未保护的α,β-不饱和羰基化合物在药物中并不常见。在这里，我们报告邻氨基酚是一种新的α,β-不饱和酮的保护基团，这是受天然产物 saccharothriolides 的启发。α,β-不饱和酮的邻氨基酚加合物，但不是α,β-不饱和酰胺或酯的加合物，会发生反迈克尔反应，生成邻氨基酚和迈克尔受体。该反应仅在质子溶剂中观察到，如甲醇和甲醇水溶液。相比之下，邻茴香胺不会从其迈克尔加合物中消除。邻氨基酚可能是一种有前途的高反应性生物活性α,β-不饱和羰基化合物的掩蔽工具。
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