2-(Fluoromethyl)-3-phytyl-1,4-naphthoquinone and Its 2,3-Epoxide. Inhibition of Vitamin K Epoxide Reductase

2-(Fluoromethyl)-3-phytyl- 1,4-naphthoquinone (7) was synthesized from the known compound 2-bromo-3-methyl-l,4-dimethoxynaphthalene by N-bromosuccinimide bromination of the 3-methyl group, conversion to the corresponding 3-fluoromethyl compound with silver fluoride, attachment of the 3-phytyl substitutent via the lithium diaryl cuprate and phytyl bromide, and then silver oxide oxidation to 7. Epoxidation with basic hydrogen peroxide gave the corresponding 2,3-oxide (1) in a very low yield. Compound 1 was not a time-dependent inhibitor of beef liver microsomal vitamin K epoxide reductase, but it was a competitive, reversible inhibitor. It was not possible to determine if 1 was a substrate for the enzyme because the expected product of reduction, namely 7, rapidly decomposed under the assay conditions.