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活性基团。它们与生物分子的非特异性反应可能是该分子低功效和意外副作用的原因。因此，未保护的 α,β-不饱和羰基在药物中并不常见。在这里，我们报告了o-氨基苯酚是一种新的 α,β-不饱和酮掩蔽基团，其灵感来自于天然产物糖草内酯。α,β-不饱和酮的o-氨基苯酚加合物，而不是 α,β-不饱和酰胺或酯的那些，经过逆迈克尔反应生成o-氨基苯酚和迈克尔受体。该反应仅在质子溶剂中观察到，例如 MeOH 和 MeOH 水溶液。相比之下，o-茴香胺没有从其迈克尔加合物中消除。o -氨基苯酚可能是高反应性生物活性α,β-不饱和羰基化合物的一种有前途的掩蔽工具。