863-61-6Relevant articles and documents
2Δ-Stereocontrolled Entry to (E)- or (Z)-Prenyl Aromatics and Quinones. Synthesis of Menaquinone-4
Garcias, Xavier,Ballester, Pablo,Capo, Magdalena,Saa, Jose M.
, p. 5093 - 5096 (1994)
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Method for producing quinone compound
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Page/Page column 4; 5, (2008/06/13)
A method for producing menatetrenone that does not have a deleterious influence on the environment, that is safe even when applied to large-scale production, and that is also simple to operate, wherein a compound represented by the following formula (1) is produced by treating with an oxygen source, and without the addition of an additive other than water or aqueous sodium chloride solution, a reaction solution consisting essentially of a solution of a compound represented by the following formula (2) dissolved in a solvent:
Bioreductive activation-independent delivery of menahydroquinone-4 via prodrug and its action in warfarin-poisoned rat liver
Takata,Karube,Hanada,Matsunaga,Matsushima
, p. 571 - 576 (2007/10/03)
The ester prodrugs of menahydroquinone-4 (menahydroquinone), the active form of menaquinone-4 (menaquinone, vitamin K(2(20)), were identified in previous reports as prodrugs that could achieve the systemic liver-specific delivery of menahydroquinone. The present study was undertaken to investigate the mechanism of the prodrugs for vitamin K-dependent carboxylation and their action in the warfarin-poisoned rat liver. A rat liver microsomal test system for assessing the carboxylation mechanism of the prodrugs was developed. In this system, the pathways for cleavage (hydrolysis) of the prodrug and for the reductive activation of menaquinone can be provided, and the vitamin K-dependent carboxylase can accept the synthetic tripeptide BOC-Glu-Glu-Leu-OMe as substrate. With this system, the carboxylation stimulated with the prodrugs and the enzymatic cleavage of the prodrugs were determined. The prodrug could stimulate the carboxylase activity in the absence of dithiothreitol, an artificial activator of the reductive activation pathway of menaquinone, and the activity order was as follows: 1-monoester > 1,4-bisester > 4-monoester. The carboxylation activities of the prodrugs were in the same order as the liver microsomal enzymatic reconversion characteristics of the prodrugs. The carboxylation activity of the selected prodrug (1-monoester) was strongly inhibited in the presence of eserine, a carboxylesterase inhibitor. The prodrug could also stimulate the carboxylase under warfarin-poisoning conditions, where the vitamin K cycle was strongly inhibited. The results confirmed that the prodrugs could generate menahydroquinone in the active site, and that the resultant menahydroquinone could act as cofactor for the carboxylase without reductive activation processes of menaquinone to menahydroquinone. Such bioreductive activation-independent vitamin K-dependent carboxylation characteristics of the prodrugs leads to enhanced pharmacological efficacy in the treatment of hypoprothrombinaemia induced in patients undergoing coumarin and cephalosporin therapies.