- Novel method for synthesizing vitamin K2
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The invention discloses a novel method for synthesizing vitamin K2. According to the method, the compound shown in the formula 4 with a brand-new structure is used as an intermediate, so that the vitamin K2 can be simply and safely synthesized at high yield. The method disclosed by the invention is beneficial to industrial production of the vitamin K2.
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Paragraph 0102-0106; 0198; 0201
(2021/01/24)
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- Method for producing quinone compound
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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:
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Page/Page column 4; 5
(2008/06/13)
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- The Friedel-Crafts allylation of a prenyl group stabilized by a sulfone moiety: Expeditious syntheses of ubiquinones and menaquinones
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An efficient synthetic method for the protected p-hydroquinone compounds 4 containing the C5 trans allylic sulfone moiety has been developed by the direct Friedel-Crafts allylation of the protected dihydroquinone 2 with 4-chloro-2-methyl-1-phenylsulfonyl-2-butene (7a) or 4-hydroxy-2-methyl-1-phenylsulfonyl-2-butene (7b). Expeditious total syntheses of coenzyme Q-10 and vitamin K2(20) have been demonstrated from these valuable key compounds 4a and 4b.
- Min, Jae-Hong,Lee, Jun-Sup,Yang, Jae-Deuk,Koo, Sangho
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p. 7925 - 7927
(2007/10/03)
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- Bioreductive activation-independent delivery of menahydroquinone-4 via prodrug and its action in warfarin-poisoned rat liver
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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.
- Takata,Karube,Hanada,Matsunaga,Matsushima
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p. 571 - 576
(2007/10/03)
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- Preparation process of naphthoquinone derivative and intermediate for the preparation thereof
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Disclosed herein are a naphthoquinone derivative represented by the following formula: STR1 wherein R1 means a hydrogen atom or methyl group, R2 is a hydrogen atom or methyl group, n stands for 0 or an integer of 1-9, and a linkage is a single bond or double bond with the proviso that if n is an integer of 2-9, the linkages may be identical with or different optionally from each other, such as a vitamin K derivative; and a process for producing the naphthoquinone derivative at a high yield without forming any geometric isomer; as well as 1,4,4a,5,8,9a -hexahydro-4a α-alkenyl-1α,4α-methanoanthraquinone derivatives and 1,4,4a,5,8,9a -hexahydro-1α,4α-methanoanthraquinone derivatives which are useful as intermediates for the preparation of the naphthoquinone derivatives.
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- Vitamin K prodrugs: 1. Synthesis of amino acid esters of menahydroquinone-4 and enzymatic reconversion to an active form
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The efficacy and toxicity of vitamin K depends on the pathway and the extent of enzymatic reductive activation to vitamin K hydroquinone, which is an essential cofactor for the synthesis of clotting factors. Parenteral use of vitamin K is impaired by its water insolubility. With the aim to improve delivery problems associated with menahydroquinone-4 (MKH, 2), an active form of menaquinone-4, N,N-dimethylglycine esters of 2 (1-mono, 4-mono, and 1,4-bis) were synthesized and assessed as potential water-soluble prodrugs for parenteral use, The esters can deliver the hydroquinone to its active site without a quinone reductive activation step. The hydrochloride salts of the esters were found to be quite soluble in water. The hydrolysis of the esters in 20% rat liver homogenate 9000 x g supernatant, rat plasma and phosphate buffer, pH 7.4, at 37°C was kinetically studied in the presence and absence of an esterase inhibitor. The hydrolysis was catalyzed by esterases located in the rat liver and rat plasma and quantitatively yielded 2. These results suggest that esterification of 2 with N,N-dimethylglycine is a promising way for obtaining water-soluble prodrug forms of 2. Based on the high susceptibility to liver esterase, the esters are potential prodrugs for achieving the site-specific delivery of 2.
- Takata,Karube,Hanada,Matsunaga,Matsushima,Sendo,Aoyama
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- Synthetic Studies on Isoprenoidquinones. II. Syntheses of Ubiquinone-10, Phylloquinone, and Menaquinone-4 by a Chain-Extending Method Utilizing Terminally Functionalized Isoprenoidhydroquinones
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Physiologically active polyisopreoidquinones, ubiquinone-10 (coenzyme Q10), phylloquinone (vitamin K1), and menaquinone-4 (vitamin K2(20)) were synthesized by a chain-extending method utilizing protected hydroquinones with the omega-hydroxyprenyl or omega-hydroxygeranyl side chain.Conditions for reductive desulfurization subsequent to allylic homologation was investigated. Keywords - polyisoprenoidquinone synthesis; ubiquinone-10; phylloquinone; menaquinone-4; chain-extending method; sulfone coupling; reductive desulfurization
- Masaki, Yukio,Hashimoto, Kinji,Kaji, Kenji
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p. 3959 - 3967
(2007/10/02)
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