Synthesis of new vitamin K derivatives with a ketone group at the C-1′ position of the side chain and their conversion to menaquinone-4

Prior to being utilized in the body, dietary vitamin K homologues are converted to menaquinone-4 (MK-4) by cleavage of the side chain part followed by prenylation. We predicted that the prenylation would occur due to the electron deficiency at the C-1′ position of the allyl moiety. Therefore, as an alternative method to make the C-1′ position electron-deficient, a new vitamin K derivative was synthesized by introducing a ketone group, and its conversion to MK-4 was investigated. Introduction of a ketone group at the C-1′ position of the side chain of 2′,3′-dihydrophylloquinone, which is known to resist conversion to MK-4, induced conversion to the MK-4 analog to a degree similar to that of natural phylloquinone. Thus, the electron deficiency at the C-1′ position is important for the conversion to MK-4.