The Synthesis of Naturally Occurring Vitamin K and Vitamin K Analogues

A number of life’s key biochemical processes, including blood coagulation, bone metabolism and cell growth, are mediated by a family of natural products referred to as the K vitamins [1]. Much work has been carried out in recent times to elucidate the mechanisms by which these compounds elicit their activity, and a number of proteins that are vitamin K-dependent have been identified in a variety of human tissues including the kidneys, spleen, lungs, uterus, placenta, thyroid, thymus, testes, and bones. As might be expected this commonality in function is reflected in a commonality in structure within this class of vitamin, i.e. they contain a naphthoquinone core, the substitution of which defines the exact K vitamin. For example, vitamin K1 (phylloquinone) 1 has a 3-phytyl substituent while vitamin K2 (menaquinone) 2 contains repeating unsaturated isoprene units at the 3 position. The menaquinones may be denoted as MK-n, where n is the number of repeating isoprene units (see Figure 1). The other form of vitamin K commonly encountered is 2methyl-1,4-naphthoquinone (vitamin K3 or menadione) 3 which lacks substitution at the 3 position. Although biologically active in vivo this compound is not found in nature.