TY - JOUR
T1 - 2-(Fluoromethyl)-3-phytyl-1,4-naphthoquinone and Its 2,3-Epoxide. Inhibition of Vitamin K Epoxide Reductase
AU - Silverman, Richard B
AU - Oliver, John S.
PY - 1989/9/1
Y1 - 1989/9/1
N2 - 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.
AB - 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.
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U2 - 10.1021/jm00129a019
DO - 10.1021/jm00129a019
M3 - Article
C2 - 2769684
AN - SCOPUS:0024456671
VL - 32
SP - 2138
EP - 2141
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 9
ER -