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.(c) 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Automated summary

Prior to utilization in the body, dietary vitamin K homologues undergo conversion to MK-4 through cleavage of the side chain and prenylation. The electron deficiency at the C-1' position of the allyl moiety is crucial for prenylation. A new vitamin K derivative with a ketone group was synthesized, and its conversion to MK-4 was investigated. The introduction of the ketone group at the C-1' position induced conversion to MK-4 analog, similar to natural phylloquinone.