- Preparation method of vitamin K1 with different cis-trans isomer proportions and intermediate halogenated phytol thereof
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The invention discloses a preparation method of vitamin K1 with different cis-trans isomer proportions and an intermediate halogenated phytol thereof. The method comprises the following steps: carrying out a halogenation reaction on a raw material phytol and phosphorus trihalide under the catalysis of phosphoric acid to obtain halogenated phytol, reacting the halogenated phytol with cyclopentadienyl menadione, and carrying out high-temperature depolymerization to obtain the vitamin K1. The addition amount of phosphoric acid in the halogenation reaction can be controlled, so that the proportionof the obtained vitamin K1 cis-isomer can be regulated between 1% and 21%.
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Paragraph 0046; 0048-0049; 0051-0052; 0054-0056; 0058-0060
(2020/06/05)
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- METHOD OF MAKING VITAMIN K1
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This invention discloses a method of making vitamin K1. The mentioned method of making vitamin K1 comprises performing a first one-pot synthesis with base catalyst, performing a first hydrolysis, performing a substitution, and performing a second one-pot synthesis without metal oxidant. The starting material of this invention is stable 2-methyl-1,4-naphthoquinone. Preferably, this invention provides a method of making vitamin K1 efficiently on simplifying the operation and decreasing the side-product. More preferably, without metal residue, the vitamin K1 of this invention is without metal residue and more safety for clinical application.
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- A METHOD OF MAKING VITAMIN K1
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This invention discloses a method of making vitamin K1. The mentioned method of making vitamin K1 comprises performing a first one-pot synthesis with base catalyst, performing a first hydrolysis, performing a substitution, and performing a second one-pot synthesis for oxidation reaction without using metal oxidant. The starting material of this invention is stable 2-methyl-1,4-naphthoquinone. Preferably, this invention provides a method of making vitamin K1 efficiently on simplifying the operation and decreasing the formation of side-product. More preferably, without the usage of metal residue in this invention results that the vitamin K1 is more safety for clinical application.
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- Method for synthesizing vitamin K1
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The invention relates to a method for synthesizing vitamin K1, relating to the technical field of synthesis of organic matters. The method comprises the following steps: reducing 2-methyl1,4-naphthoquinone to 2-methyl-1,4-naphthalenediol in certain solvents by virtue of a reducing agent under certain conditions, then adding phytol, reacting by using an appropriate catalyst under certain conditions to synthesize 2-methyl3-phytyl1,4-naphthalenediol, then oxidizing the 2-methyl3-phytyl1,4-naphthalenediol by using an appropriate oxidizing agent to obtain vitamin K1, and decompressing and concentrating to obtain the vitamin K1. According to the method for synthesizing the vitamin K1, the 2-methyl1,4-naphthoquinone is used as a raw material, and the hydroxyl groups are not required to be protected, so that the method has the characteristics of simple process, moderate reaction conditions, high productivity, high product purity and high yield; moreover, the method is low in production cost and very suitable for industrialized production.
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- Ruthenium-catalyzed oxidative dearomatization of phenols to 4-(tert-butylperoxy)cyclohexadienones: Synthesis of 2-substituted quinones from p-substituted phenols
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The ruthenium-catalyzed oxidation of phenols with tert-butylhydroperoxide efficiently gives the corresponding 4-(tert-butylperoxy)cyclohexadienones. The oxidation proceeds selectively because of ruthenium's ability for rapid single-electron transfer. This biomimetic oxidation reaction is highly useful to obtain the metabolic compounds desired for confirming the safety of medicines and related compounds. Typically, the first metabolic compound of the female hormone estrone is readily obtained by this biomimetic oxidation reaction. The resulting 4-(tert-butylperoxy)cyclohexadienones are versatile synthetic intermediates, which can be transformed into 2-substituted 1,4-benzoquinones by treatment with acid catalysts. Acid-promoted rearrangement followed by a Diels-Alder reaction provides a new strategy for the synthesis of fused cyclic compounds, such as naphthoquinone and anthraquinone derivatives, from readily available phenols. The nonnatural 1,4-diacetoxy steroidal skeleton is obtained by the oxidation of estrone followed by zinc-mediated migration. Vitamin K 3 is synthesized selectively from p-cresol in an overall 79 % yield in 4 steps, and the synthesis includes the ruthenium-catalyzed oxidation.
- Murahashi, Shun-Ichi,Miyaguchi, Noriko,Noda, Shinji,Naota, Takeshi,Fujii, Akiko,Inubushi, Yasutaka,Komiya, Naruyoshi
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p. 5355 - 5365
(2011/11/14)
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- Synthesis of 2-substituted quinones, vitamin K3, and vitamin K1 from p-cresol. BF3·OEt2-catalyzed methyl migration of 4-tert-butyldioxycyclohexadienones
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BF3·OEt2-catalyzed methyl group migration of 4-methyl-4-tert-butyldioxycyclohexadienone, which is obtained by ruthenium-catalyzed oxidation of p-cresol with tert-butyl hydroperoxide, in hexafluoro-2-propanol/toluene gave toluquinone efficiently. The reaction can be applied to the regio-selective short-step syntheses of vitamin K3 and vitamin K1 from p-cresol.
- Murahashi, Shun-Ichi,Fujii, Akiko,Inubushi, Yasutaka,Komiya, Naruyoshi
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scheme or table
p. 2339 - 2341
(2010/05/19)
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- NUTRITIONAL FORMULATION
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The present invention relates to nutritional supplements that provide an adult with essential vitamins and minerals that may be lacking in the adult's diet and prevent chronic diseases, such as osteoporosis. A number of combinations of nutrients in set ratios are provided to increase the body's ability to absorb and use the nutrients. These combinations are important in helping the body reach the proper balance required for maximized function. Because adults over the age of 50 years have different nutritional needs, nutritional supplements specifically designed for them are also provided.
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- Nutritional supplement
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A nutritional supplement is provided that is designed to provide nutritional benefits as well as to assist the body with detoxification. By providing a supplement that serves both of these functions, the present invention may enable persons to improve their overall wellness.
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- Improved synthesis of vitamin K1
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With (E/Z)-isomeric phytyl halides as side-chain materials, vitamin K1 is synthesized via a Diels-Alder reaction to activate the free bridgehead hydrogen of 3 for the alkylation and a retro-Diels-Alder reaction to eliminate cyclopentadiene from 2 in a high yield, in which the configuration of the double bond in the phytyl side-chain is retained.
- Ji, Ya-Fei,Zong, Zhi-Min,Wei, Xian-Yong,Tu, Guang-Zhong,Xu, Li,He, Lin-Tao
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p. 763 - 772
(2007/10/03)
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- A convenient and asymmetric protocol for the synthesis of natural products containing chiral alkyl chains via Zr-catalyzed asymmetric carboalumination of alkenes. Synthesis of phytol and vitamins E and K.
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[reaction: see text]. A convenient and asymmetric protocol for the synthesis of chiral oligoisoprenoids is described. Typically, a C14 vitamin E side chain 5 was synthesized in 47% yield over four steps. Isomeric purity of 5 was upgraded to >99% R at C-2 and 97% R at C-6 by the statistical formation of stereoisomeric p-phenylenebisurethanes and their diastereomeric separation. In addition, phytol and vitamin K were synthesized in 21% and 28% overall yields, respectively, over five steps from 1.
- Huo,Negishi
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p. 3253 - 3256
(2007/10/03)
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- Compositions and methods for prevention and treatment of chronic diseases and disorders including the complications of diabetes mellitus
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This invention relates to nutrient and therapeutic compositions for treatment and prevention of symptoms and disease conditions associated with microangiopathy and macroangiopathy and to methods using the compositions. In particular, the invention relates to compositions useful in the treatment of diabetic retinopathy and nephropathy, to compositions useful in the treatment of other retinal disorders including macular degeneration and cataracts, to compositions useful in wound healing, to compositions useful for treatment and prevention of neuropathy, to compositions useful for treatment and prevention of cardiovascular disease and to compositions useful for the treatment and prevention of dental and periodontal disorders.
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- An expeditious route to CoQ(n), Vitamins K1 and K2, and related allylated para-quinones utilizing Ni(0) catalysis
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Coupling reactions between vynylalanes and chloromethylated para-quinones, mediated by catalytic amounts of Ni(0), lead directly to allylated products, including coenzyme Q, and vitamins K1 and K2.
- Lipshutz, Bruce H.,Kim, Sung-Kyu,Mollard, Paul,Stevens, Kirk L.
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p. 1241 - 1253
(2007/10/03)
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- Method of making vitamin K1
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A process for the preparation of vitamin K1 by the oxidation of an alkali metal salt of dihydrovitamin K1 with hydrogen peroxide in the presence of an iron (III) salt at a pH of 13.7 to 14.3. The dihydrovitamin K1 alkali metal salt is produced by the saponification of a dihydrovitamin K1 diester with sodium hydroxide or potassium hydroxide. Conveniently, the oxidation process follows the saponification of dihydrovitamin K1 without isolation of the product of the saponification reaction.
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- A Convenient One-flask Synthesis of Vitamin K
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A facile synthesis of highly pure (E)-form vitamins K1 and K2 by the reaction of 3-substituted isobenzofuranones 2 with vinylic sulfones 1 in one flask is described.
- Tso, Hsi-Hwa,Chen, Yu-Jiun
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p. 104 - 105
(2007/10/03)
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- The active site of vitamin K and the role of the vitamin K-dependent carboxylase
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Vitamin K is the blood-clotting vitamin. It participates in the blood coagulation cascade as a carboxylase cofactor. Enzymic oxygenation of vitamin K hydroquinone provides the driving force for the carboxylation of selected glutamates in the proteins of the blood-clotting cascade. The active site of vitamin K has now been defined by 18O-labeling experiments. The oxygenation is completely specific for the carbonyl group adjacent to the quinone methyl group of vitamin K. The experiment makes use of the 18O-labeled vitamin K isotopomers 9 and 10. Thus, oxygenation of 9 with 16O2 occurs at the carbonyl group next to methyl, as shown by exchange of the 18O label at that position. Synthesis of the two 18O-labeled vitamin K isotopomers 9 and 10 was accomplished by cerium(IV)-mediated oxidation in the presence of H218O of the corresponding methyl half-ethers 4 and 8. The position of the label was ascertained by 13C and heteronuclear NOE NMR spectroscopies. A role for the active site thiols on the vitamin K-dependent carboxylase is also suggested. The thiolate anion is an excellent candidate for the weak base that initiates the base strength amplification sequence leading to carboxylation and vitamin K oxide formation.
- Naganathan, Sriram,Hershline, Roger,Ham, Seung Wook,Dowd, Paul
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p. 9831 - 9839
(2007/10/02)
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- Catalytic Oxidation of Hydroquinones and Naphthalenediols to 1,4-Quinones with H2O2 in the Presence of Chromium (VI) Oxide-Bistributyltin Oxide and an Application to Vitamin K1 Synthesis
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The oxidation of hydroquinones and naphthalenediols to 1,4-quinones was carried out in the presence of a chromium (VI) compound formed from chromium (VI) oxide and bistributyltin oxide with 30percent aqueous H2O2 in benzene-isopropyl ether at 50 deg C.The catalyst was fixed on charcoal and used for the oxidation of dihydrovitamin K1 in ethyl alcohol.
- Inoue, Masami,Uragaki, Toshitaka,Enomoto, Saburo
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p. 2075 - 2078
(2007/10/02)
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- REAKTIONEN VON KOMPLEXLIGANDEN. XXIV. SYNTHESE VON NAPHTHOL-DERIVATEN AUS CARBONYL-CARBEN-KOMPLEXEN UND ALKINEN: REGIOSELEKTIVER EINBAU DES ALKINS IN DAS NAPHTHALIN-GERUEST
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Pentacarbonyl(methoxyphenylcarbene)chromium reacts with various alkynes to give tricarbonyl(4-methoxy-1-naphthol)chromium complexes.Aliphatic n-1-alkynes yield regiospecifically 2-alkylnaphthol compounds; 2-alkynes, however, lead to mixtures of 2,3-dialky
- Doetz, Karl Heinz,Muehlemeier, Jochen,Schubert, Ulrich,Orama, Olli
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p. 187 - 202
(2007/10/02)
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- CROSS-COUPLING REACTION OF ALLYL BROMIDES WITH ORGANOTIN REAGENTS CATALYZED BY ZINC CHLORIDE
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Myrcene and β-farnesene have been synthesized by the zinc chloride catalyzed coupling reaction of (2-methylene-3-butenyl)trimethyltin with prenyl bromide and geranyl bromide, respectively; vitamin K1 was synthesized by a similar coupling reaction.
- Godschalx, J. P.,Stille, J. K.
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p. 1905 - 1908
(2007/10/02)
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- A Chemical Model for the Mechanism of Vitamin K Epoxide Reductase
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The reactions of Vitamin K1 epoxide and 2,3-dimethylnaphthoquinone epoxide with dithiothreitol and mercaptoethanol have been studied as a potential model for the mechanism of the enzyme vitamin K epoxide reductase.The reaction proceeds with thiol addition to open the oxirane ring, yielding preferentially the 2-thio-3-hydroxy adduct in the case of vitamin K1 epoxide.Reaction with a second thiol group results in reductive cleavage of this adduct and elimination of water to yield the quinones.All steps are catalyzed by triethylamine.Evidence for a hydroxy-substituted 2,3-dihydronaphthoquinone enolate intermediate in the second step is found in the observation of the corresponding keto compounds as equilibrated side products in the reaction with dithiothreitol.With this reagent, intramolecular reaction to form the cyclic disulfide permits cleavage of the thiol adduct under mild conditions where protonation of the enolate is rapid relative to elimination of the hydroxyl.Isolation and characterization of the intermediates and their conversion to the quinones are described.
- Preusch, Peter C.,Suttie, J. W.
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p. 3301 - 3305
(2007/10/02)
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- Vitamin Syntheses via Carbene Complexes II. Carbonyl Carbene Complex Induced Synthesis of Vitamines of the K1 and K2 Series
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Pentacarbonyl(methoxyphenylcarbene)chromium(0) (1) reacts with the isoprenoid enynes 2 - 6 to give the tricarbonyl(dihydrovitamin K)chromium complexes 7 - 11.Oxidation of 7 - 11 with silver(I) oxide leads to the vitamines of K1 and K2 series 17 - 21, whereas the 5 - 10-η6-isomeres 12 - 16 yield the tricarbonyl(vitamin K)chromium komplexes 22 - 26.The syntheses proceed stereospecifically with respect to the isoprenoid side chain.
- Doetz, Karl Heinz,Pruskil, Ingrid,Muehlemeier, Jochen
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p. 1278 - 1285
(2007/10/02)
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- Process for preparing vitamin K
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A process for preparing vitamins of the vitamin K1 and K2 series in their E-isomeric form through the reaction of a phenylcarbene metal complex with an enyne and intermediates in this synthesis.
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- Organocopper Chemistry of Quinone Bisketals. Application to the Synthaais of Isoprenoid Quinone Systems
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The reactions of organocuprates of 1,4-benzoquinone and 1,4-naphthoquinone bisketals are reported.These reagents, formed from the corresponding lithium reagent, cuprous iodide, and dimethyl sulfide react efficiently with allylic bromides (allyl, prenyl, geranyl, and phytyl), often with utilization of greater than one R group of the R2CuLi.Their reactions with acid chlorides and benzyl bromide proceed with acceptable efficiency, but they are unreactive toward a number of other substrates.The utility of this chemistry in the synthesis of menaquinone-2, phylloquinone,cymopol, and cymopol methyl ether is described.
- Chenard, Bertrand L.,Manning, Michael J.,Raynolds, Peter W.,Swenton, John S.
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p. 378 - 384
(2007/10/02)
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- Production of vitamin K1 and vitamin K2
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A process for producing hydro-precursors for vitamin K1 and vitamin K2 which comprises reacting (A) 2-methylhydronaphthoquinone-1,4 with (B) a compound selected from the group consisting of phytyl bromide, isophytyl bromide, geranyl bromide, farnesyl bromide, geranylgeranyl bromide and the corresponding chlorides in a reaction system which comprises an aqueous phase comprising an aqueous solution of an alkali and an oily phase comprising a hydrophobic organic solvent, in the presence of a salt comprising a quaternary ammonium ion or a tetraalkyl phosphonium ion represented by the formula (I) or formula (II): STR1 wherein R1, R2, R3 and R4 each represent an alkyl or aralkyl group containing from 1 to 20 carbon atoms and the sum of the carbons in R1, R2, R3 and R4 groups is at least 12. The resultant hydro-precursor is oxidized to convert it into vitamin K1 or vitamin K2.
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