Discovery of Presaccharothriolide X, a Retro-Michael Reaction Product of Saccharothriolide B, from the Rare Actinomycete Saccharothrix sp. A1506

• Published in: Organic letters Vol. 20; no. 15; pp. 4406 - 4410
• Main Authors: Lu, Shan, Nishimura, Shinichi, Takenaka, Kei, Ito, Masashi, Kato, Taira, Kakeya, Hideaki
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 03-08-2018
• Subjects: Actinobacteria - chemistry; Aminophenols - chemistry; Anti-Infective Agents - chemistry; Cell Line, Tumor; Cell Proliferation - drug effects; Cytotoxins - chemistry; Cytotoxins - pharmacology; Humans; Macrolides - chemistry; Macrolides - pharmacology; Molecular Structure; Oxidation-Reduction; Schizosaccharomyces - cytology; Schizosaccharomyces - drug effects
• ISSN: 1523-7060; 1523-7052
• DOI: 10.1021/acs.orglett.8b01535

The highly reactive precursor molecule, presaccharothriolide X, was successfully isolated from the rare actinomycete Saccharothrix sp. A1506. The comparable biological activity of presaccharothriolide X and its Michael addition product saccharothriolide B unveils a unique masking/activating property of 2-aminophenol. Unexpectedly, 2-aminophenol in saccharothriolide B was eliminated through a retro-Michael reaction, to yield presaccharothriolide X under physiological conditions. 2-Aminophenol might be developed into a useful protecting group for bioactive small molecules with an α,β-unsaturated ketone.