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Published on: August 14, 2019
Efficient Syntheses of Vitamin K Chain-Shortened Acid Metabolites
Aaron M Teitelbaum1, Michele Scian1, Wendel L Nelson1
1Department of Medicinal Chemistry, School of Pharmacy, University of Washington, Seattle, WA 98195.
Abstract:
Vitamin K sequentially undergoes ω-oxidation followed by successive rounds of β-oxidation to ultimately produce two chain-shortened carboxylic acid metabolites, vitamin K acid 1 and vitamin K acid 2. Two facile syntheses of these acid metabolites are described, each starting from commercially available menadione-cyclopentadiene adduct 3. Vitamin K acid 1 was synthesized in five steps via alkylation with a geranyl halide followed by subsequent oxidation reactions, while fully retaining the trans configuration of the side chain 2',3'-double bond. Vitamin K acid 2 was synthesized in 5 steps from 3via alkylation with dimethylallyl chloride and subsequent oxidation reactions.
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