Systematic synthesis and anti-inflammatory activity of ω-carboxylated menaquinone derivatives-Investigations on identified and putative vitamin K2 metabolites

Vitamin K is an essential nutrient for blood coagulation and bone homeostasis, and also functions in many physiological processes including inflammation and cancer progression. However, the nature and activities of its metabolites remain unclear. We report here systematic synthesis of omega-carboxylated derivatives of menaquinone (vitamin K-2), including previously identified metabolites 5, K acid I (10), and K acid II (12), and evaluation of their inhibitory activity toward LPS-stimulated induction of inflammatory cytokines. These results should contribute to an improved understanding of the biochemistry and pharmacology of vitamin K. (C) 2015 Elsevier Ltd. All rights reserved.