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Amidation Strategy for Final-Step ?-Hydroxytropolone Diversification.

ABSTRACT: ?-Hydroxytropolones (?HTs) are excellent metalloenzyme-inhibiting fragments that have been the basis for the development of potent inhibitors of various therapeutically important enzymes. The following manuscript describes a final-step amidation approach for ?HT diversification. The method takes advantage of a scalable, chromatography-free synthesis of a carboxylic acid-appended ?HT, and in the present manuscript we describe the synthesis of eight amide-containing ?HTs, three of which we envision using as chemical probes. We expect that the general strategy will find widespread usage in both chemical biology and medicinal chemistry studies on ?HTs.

SUBMITTER: Berkowitz AJ

PROVIDER: S-EPMC6411066 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Amidation Strategy for Final-Step α-Hydroxytropolone Diversification.

Berkowitz Alex J AJ Abdelmessih Rudolf G RG Murelli Ryan P RP

Tetrahedron letters 20180630 31

α-Hydroxytropolones (αHTs) are excellent metalloenzyme-inhibiting fragments that have been the basis for the development of potent inhibitors of various therapeutically important enzymes. The following manuscript describes a final-step amidation approach for αHT diversification. The method takes advantage of a scalable, chromatography-free synthesis of a carboxylic acid-appended αHT, and in the present manuscript we describe the synthesis of eight amide-containing αHTs, three of which we envisio ...[more]

PMID: 30872871

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