- Microflow High-p,T Intensification of Vitamin D3 Synthesis Using an Ultraviolet Lamp
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Herewith a new process concept for synthesis is presented which combines both UV-photoirradiation and high-p,T intensification (photo-high-p,T) in continuous flow. The application of this procedure to Vitamin D3 synthesis promotes thermal shifting of the equilibrium from the reaction intermediate to the product. This is enabled by microreactors which allow operation under harsh conditions such as the high temperature used here. This provides, to our best knowledge, a new kind of process combination (novel process window). As a result, in less than 1 min, 42% conversion of 7-dehydrocholesterol can be achieved giving a 17% yield and 40% selectivity of Vitamin D3. This approach enhances productivity by up to 2 orders of magnitude compared with the current capillary based vitamin D3 synthesis, because, under the microflow conditions, photochemistry can be performed at fairly high concentration and up to 20 times faster.
- Escribà-Gelonch, Marc,No?l, Timothy,Hessel, Volker
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- Photochemical transformations of 7-dehydrocholesterol
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Photochemical transformations of 7-dehydrocholesterol were performed with a two-lamp experimental circulation installation equipped with a ferrioxalate actinometer and were monitored by UV spectroscopy and high-performance liquid chromatography. The quant
- Grigoryan,Martiryan,Nersesyan,Markaryan
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Read Online
- Preparation method of vitamin D3
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The invention provides a preparation method of vitamin D3, which comprises the following steps: by taking a compound A as a substrate, sequentially carrying out photochemical reaction, thermal isomerization reaction, crystallization and hydrolysis reaction to obtain the vitamin D3, wherein the compound A has a structure as shown in a formula I in the specification, Rb is one of Rb and Ra is an electron donating group; the illumination condition is ultraviolet irradiation. When the method is used for preparing the vitamin D3, the high-purity vitamin D3 crystal can be prepared without column chromatography, and the method is suitable for large-scale production, high in yield and strong in controllability.
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- Novel industrial method for preparing vitamin D3 by taking stigmasterol as raw material
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The invention provides a novel industrial method for preparing vitamin D3 by taking stigmasterol as a raw material. The method comprises the following steps: sequentially carrying out hydroxyl acetylation, side chain oxidation, side chain isopentane reduction and hydrogenation on stigmasterol to obtain cholesterol acetate, and then sequentially carrying out oxidation, hydrazone formation, hydrazone removal, hydrolysis, illumination and the like to obtain the vitamin D3. The invention provides a novel method for preparing vitamin D3 from stigmasterol, and the method has the advantages of mild reaction conditions and high yield, and is suitable for industrial production.
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- Vitamin D3 purification method
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The invention discloses a vitamin D3 purification method which comprises the following steps: a1, mixing organic amine, a first organic solvent, vitamin D3 oil and aryl chloride to react, and then adding water to stop the reaction; a2, washing the product obtained in the step a1 with water, performing drying and filtering, carrying out reduced pressure distillation, performing dissolving, carryingout secondary reduced pressure distillation, carrying out cooling and crystallizing; b1, dissolving vitamin D3 methyl benzoate in methanol, and dropwise adding a strong alkaline solution to perform reacting; b2, carrying out reduced pressure distillation on the substance obtained in the step b1, then carrying out liquid separation, washing an organic phase with water, and carrying out drying, filtering, carrying out secondary reduced pressure distillation, dissolving, cooling and recrystallizing; c1, dissolving the vitamin D3 crude product in a third organic solvent, and then performing stirring for decolorization; and c2, filtering the product obtained in the step c1, carrying out reduced pressure distillation on the filtrate, and carrying out dissolving, cooling, recrystallizing, filtering, and drying to obtain the vitamin D3. The vitamin D3 purified by the purification method disclosed by the invention has the advantages of higher purity, lower harmful impurity content and higher stability.
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- IRRADIATION PROCESS OF PRO VITAMIN D
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The invention discloses an improved process for production of vitamin D3 from 7- dehydrocholesterol (7- DHC) and to a simple process for recovery unreacted 7-DHC for further reuse. The invention further describes a process for isolation and purification of Vitamin D3.
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Page/Page column 14; 15
(2020/11/30)
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- IMPROVED PHOTOCHEMICAL SYNTHESIS OF VITAMIN D3 USING SENSITIZERS
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The present invention discloses an improved photochemical synthesis of vitamin D3 from 7-dehydrocholesterol alone or in combination with sterol precursors in presence of the photosensitizer of Formula I in high yield and with reduced levels of impurities.
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Page/Page column 16-17; 19-27
(2020/12/01)
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- Synthesis method of vitamin D3 analogue
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The invention discloses a synthesis method of a vitamin D3 analogue. The invention discloses a photochemical reaction method of preparing a cis-intermediate (I) from a trans-initiator (II). The prepared intermediate can be used as an intermediate for the synthesis of active vitamin D analogy such as alfacalcidol, calcitriol, and the like. The synthesis conditions of the active substances become mild, the side reactions are reduced, and the yield is increased.
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Paragraph 0033-0037
(2019/08/30)
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- New industrial method for producing vitamin D3 by taking wool fat as raw material
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The invention provides a new industrial method for producing vitamin D3 by taking wool fat as a raw material. The new industrial method comprises the following steps: carrying out saponification and primary purification on the wool fat in a low alcohol solution, thus obtaining a cholesterol crude product; directly carrying out acetylation on the cholesterol crude product, thus obtaining high-purity cholesterol acetate; then sequentially carrying out oxidizing, hydrazone forming, hydrazone removing, hydrolyzing, illuminating and the like, thus obtaining the vitamin D3. A production technology disclosed by the invention is efficient, green and environment-friendly, is high in product yield and is suitable for industrial production, and the manufacturing cost of the vitamin D3 is greatly reduced; a saponification technology is ingenious in filtrate treatment, has no generation of waste liquid and waste and is more beneficial for environment protection.
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- Syntheses of 7-dehydrocholesterol peroxides and their improved anticancer activity and selectivity over ergosterol peroxide
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7-Dehydrocholesterol peroxide (5α,8α-epidioxycholest-6-ene-3β-ol, CEP) and its acetate and hemisuccinate derivatives were synthesized and isolated for the first time, which exhibit improved anticancer activity and selectivity over ergosterol peroxide (5α,8α-epidioxy-22E-ergosta-6,22-dien-3β-ol, EEP), showing potential as new chemotherapeutic agents.
- Tian, Na-Na,Li, Chao,Tian, Na,Zhou, Qian-Xiong,Hou, Yuan-Jun,Zhang, Bao-Wen,Wang, Xue-Song
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p. 14843 - 14846
(2017/12/15)
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- METHODS FOR IMPROVED PRODUCTION OF VITAMINS D2 AND D3
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It is an object of the present invention to provide methods for producing vitamin D that gives improved yields and reduced side product contamination. In various aspects, these methods provide for production of vitamin-D2 using ergosterol as provitamin D2 or a dihydroxy derivative thereof as a starting material, or production of vitamin-D3 using 7-dehydrocholesterol as provitamin D3 or a dihydroxy derivative thereof as the starting material. The methods described herein comprise irradiating the starting material in a solution including an organic or inorganic base with light in the wavelength range 245-360 nanometers (nm) to obtain a product containing pre-vitamin-D2 or pre-vitamin-D3, and heating the product to convert the resulting pre-vitamin-D2 or pre-vitamin-D3 to vitamin D2 or vitamin D3. In various embodiments, these methods further comprise recovering vitamin D2 or vitamin D3 from this reaction as a purified product.
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Paragraph 0041-0045
(2016/07/05)
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- Probing the structural requirements for vitamin D3 inhibition of the hedgehog signaling pathway
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A structure-activity relationship study to elucidate the structural basis for hedgehog (Hh) signaling inhibition by vitamin D3 (VD3) was performed. Functional and non-functional regions of VD3 and VD2 were obtained through straightforward synthetic means
- Deberardinis, Albert M.,Banerjee, Upasana,Miller, Michele,Lemieux, Steven,Hadden
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scheme or table
p. 4859 - 4863
(2012/08/13)
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- Continuous-flow synthesis of vitamin D3
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A highly efficient, two-stage, continuous-flow synthesis of vitamin D 3 from provitamin D3 was achieved. The developed method afforded the desired product in high yield (HPLC-UV: 60%, isolated: 32%) and required neither intermediate purification nor high-dilution conditions. The Royal Society of Chemistry 2010.
- Fuse, Shinichiro,Tanabe, Nobutake,Yoshida, Masahito,Yoshida, Hayato,Doi, Takayuki,Takahashi, Takashi
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scheme or table
p. 8722 - 8724
(2011/02/24)
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- Photo-conversion of two epimers (20R and 20S) of pregna-5,7-diene-3β, 17α, 20-triol and their bioactivity in melanoma cells
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Pregna-5,7-dienes and their hydroxylated derivatives can be formed in vivo when there is a deficiency in 7-dehydrocholesterol (7-DHC) Δ-reductase function, e.g., Smith-Lemli-Opitz syndrome (SLOS). Ultraviolet B (UVB) radiation induces photoconversion of 7-DHC to vitamin D3, lumisterol3 and tachysterol3. Two epimers (20R and 20S) of pregna-5,7-diene-3β,17α,20-triol (4R and 4S, respectively) were synthesized and their UVB photo-conversion products identified as corresponding 9,10-secosteroids with vitamin D-like and tachysterol-like structures, and 5,7-dienes with inverted configuration at C-9 and C-10 (lumisterol-like). The number and character of the products and the dynamics of the process were dependent on the UVB dose. At high UVB doses, the formation of multiple oxidized derivatives of the primary products, and the formation of 5,7,9(11)-triene, were observed. The production of vitamin D-like, tachysterol-like and lumisterol-like derivatives was also observed in human skin treated with 4R and 4S, and subjected to UV irradiation, as shown by RP-HPLC. Newly synthesized compounds inhibited melanoma growth in dose dependent manner, and some of them showed equal or higher potency than 1,25(OH)2D3. In summary, we have characterized for the first time the products of UV induced conversion of pregna-5,7-diene-3β,17α,20-triols and documented that the newly synthesized compounds have antiproliferative properties against melanoma cells.
- Zmijewski, Michal A.,Li, Wei,Zjawiony, Jordan K.,Sweatman, Trevor W.,Chen, Jianjun,Miller, Duane D.,Slominski, Andrzej T.
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scheme or table
p. 218 - 228
(2009/04/14)
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- Efficient convergent synthesis of 1alpha,25-dihydroxyvitamin D3 and its analogues by Suzuki-Miyaura coupling.
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[reaction: see text] 1alpha,25-Dihydroxyvitamin D(3) was synthesized by the Suzuki-Miyaura coupling of the A-ring intermediate 1, which was efficiently prepared from readily available 1,7-enyne 2, with the corresponding boronate compound of the C,D-ring portion. The method was applied to prepare des-C,D analogues of 1alpha,25-dihydroxyvitamin D(3).
- Hanazawa, Takeshi,Koyama, Akiko,Wada, Takeshi,Morishige, Eiko,Okamoto, Sentaro,Sato, Fumie
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p. 523 - 525
(2007/10/03)
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- Vitamin/Mineral Compositions with DHA
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Compositions containing the fatty acid docosahexaenoic acid (DHA) in combination with at least one vitamin and mineral are provided to supplement nutrition in a mammalian diet. DHA is present in the composition in concentrated amounts, advantageously in a carrier such as marinol oil, to allow for quantities of DHA sufficient to supply expectant and new mothers and their children as recommended on a daily basis. This DHA may also be used to treat a variety of disorders in children and adults. The compositions advantageously include vitamins, minerals, and optionally other nutrients to provide a nutritional supplement which may be convenient to swallow and taken once a day.
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- VITAMIN D DERIVATIVES AND PROCESS FOR PRODUCING THE SAME
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A process for producing hydroxyvitamin D derivatives, characterized by converting a hydrogen atom or atoms at the 2-position, 24-position, 25-position and/or 26-position of a vitamin D into a hydroxyl group or groups in a solution containing a microorganism that belongs to the genus Nocardia, Streptomyces,Sphingomonas or Amycolata which has an ability to hydroxylate vitamin Ds or an enzyme produced by that microorganism, and optionally under the coexistence of a cyclodextrin; and novel vitamin D3 derivatives obtained by that process.
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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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- DNA encoding human κ casein and process for obtaining the protein
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The present invention relates to an expression system comprising a DNA sequence encoding a polypeptide which has a biological activity of human κ-casein, the system comprising a 5′-flanking sequence capable of mediating expression of said DNA sequence. In preferred embodiments the 5′-flanking sequence is from a milk protein gene of a mammal such as a casein gene or whey acidic protein (WAP) gene and the DNA sequence contains at least one intron sequence selected from the intron sequences presented in SEQ ID NO:30. The invention also relates to DNA sequences, replicable expression vectors and cells harboring said vectors, recombinant polypeptide e.g. in glycosylated form, and milk, infant formula or nutrient supplement comprising recombinant polypeptide. The invention further relates to a transgenic non-human mammal such as a mouse, rat, rabbit, goat, sheep, pig, lama, camel or bovine species whose germ cells and somatic cells contain a DNA sequence as defined above as a result of chromosomal incorporation into the non-human mammalian genome, or into the genome of an ancestor of said non-human mammal.
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- Phosphoethanolamine conjugates of vitamin D compounds
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Certain phosphoethanolamine conjugates of vitamin D compounds are disclosed wherein the phosphoethanolamine moiety is bonded at the 3-position of the vitamin D moiety. The conjugates exhibit anti-tumor, anti-psoriatic and anti-inflammatory activities in addition to those activities associated with vitamin D. The invention embraces the novel compounds, pharmaceutical compositions thereof, and their methods of use.
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- Kinetics of thermal [1,7A]-sigmatropic shift of hexafluoro vitamin D3 and vitamin D3 derivatives. Evaluation of conformations of the A ring affected by 1-OH and 3-OH groups
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The quantitative evaluation of the [1,7a]-sigmatropic rearrangement of vitamin D3 and its analogs affected by the conformations of the A ring using the 1H-NMR method was described. Although the side chain of the D ring had no effect on the hydrogen migration, the rearrangement was influenced by the hydroxy groups of the A ring.
- Igarashi, Jun-Etsu,Ikeda, Masahiko,Sunagawa, Makoto
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p. 1431 - 1436
(2007/10/03)
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- Thermal -Sigmatropic Shift of Previtamin D3 to Vitamin D3: Synthesis and Study of Pentadeuterio Derivatives
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Specifically pentadeuteriated previtamin D3 11 has been synthesized to impart thermal stability to the otherwise labile material.A 12-step synthesis of the trideuteriated A-ring 14b from p-methoxyphenol was developed and employed the addition of (methyl-d3)magnesium iodide to either the keto thiomethylene intermediate 23 or the keto dioxane 27.The enantiomerically pure trideuterio A-ring (-)-14b was then coupled with the deuteriated CD fragment 13b followed by hydrogenation to afford pentadeuteriated previtamin D3 11.A primary deuterium kinetic isotope effect (KIE) study of the -sigmatropic hydrogen migration in the conversion of previtamin D3 to vitamin D3 indicated a more "normal" primary deuterium isotope effect (as compared to a previously reported literature value of ca. 45).At 80 deg C, a kH/kD for the previtamin D3 to vitamin D3 isomerization was determined to be ca. 6.2.At 25 deg C, this -sigmatropic hydrogen migration proceeds with a kH/kD of ca. 11.4.The revisible, first-order -sigmatropic hydrogen shift of previtamin D3 to D3, determined over the temperature range 60.1-85.5 deg C is characterized by the following activation parameters: log AH = 8.8 and EaH = 19.6 kcal/mol.Deuteriated pre-D3, which rearranges over this temperature range, is characterized by the activation parameters log AD = 9.5 and EaD = 21.9 kcal/mol.
- Okamura, William H.,Elnager, Hassan Y.,Ruther, Michael,Dobreff, Susanne
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p. 600 - 610
(2007/10/02)
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- A new synthetic route to 1,25-dihydroxy-vitamin D3
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A synthesis of 1,25-dihydroxy-vitamin D3 using a new acetylenic Ring-A precursor is described. Ring-A synthons 4a or 4b can be prepared in homochiral form by a diastereoselective diazoester cyclization.
- Wilson, Stephen R.,Venkatesan,Augelli-Szafran,Yasmin
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p. 2339 - 2342
(2007/10/02)
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- Biomimetic oxidation of vitamin D by iron-sulfur model cluster and dioxygen system
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Oxidation of vitamin D3 with a combination of iron-sulfur protein model cluster, (n-Bu4N)2[Fe4S4(SPh)4], and molecular oxygen produced (5E)-10-oxo-10-norvitamin D3 and 8α-hydroxy-9,10-seco-4,6,10(19)-cholestatrien-3-one, a new type of vitamin D metabolites, mimicking biological oxidation.
- Yamamoto,Imae,Yamada
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p. 4903 - 4906
(2007/10/02)
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- ORGANIC REACTIONS AT HIGH PRESSURE. INTERCONVERSION OF PREVITAMIN D3 AND VITAMIN D3.
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The interconversion of previtamin D3 and vitamin D3 at 20 deg C was effected at high pressure (15 kbar) in three solvent mixtures.The rate constants of k1 and k2 were determined to be 30 to 45 times larger than the corresponding 1 bar rate constants.The ΔV* was calculated to be -5.14 cm3/mol or lower, indicating a concerted sigmatropic hydrogen shift.
- Dauben, William G.,Kowalczyk, Bruce A.,Funhoff, Dirk J. H.
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p. 3021 - 3024
(2007/10/02)
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- A Novel Approach to the Stereocontrolled Synthesis of Steroid Side Chains Including the CD-Ring System: The First Total Synthesis of (+)-8α-(Phenylsulfonyl)des-AB-cholestane and Its Efficient Conversion into Grundmann's Ketone and Vitamin D3
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A new stereocontrolled approach to steroid CD-ring system including side chain starting from an optically active indenedione 6 is described.The application of this finding allows for the asymmetric synthesis of des-AB-cholestane 3 and 8α-(phenylsulfonyl)des-AB-cholestane 37; from the latter Grundmann's ketone 25 and vitamin D3 (27) were synthesized efficiently.
- Nemoto, Hideo,Kurobe, Hiroshi,Fukumoto, Keiichiro,Kametani, Tetsuji
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p. 5311 - 5320
(2007/10/02)
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- A General Method for the Synthesis of 3,5-Cyclovitamin D3 and Derivatives. A Stereoselective Synthesis of Vitamin D3
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A stereoselective synthesis of vitamin D3 (1) was achieved via 3,5-cyclovitamin D3 (33) which was synthesized from the chiral aldehyde (3) and the vinyl bromide (27) derived from Grundmann's ketone (25). (+/-)-(Z)-5-(2-Cyclohexylidene-ethylidene)-4-methylenecyclohexane-r-1, t-3-diol (24) as a model compound of 1α-hydroxyvitamin D3 was also stereoselectively synthesized via the solvolysis of (+/-)-α-cyclohexylidenemethyl-3β-methoxymethoxy-2-methylenebicyclohexane-1-methanol (21) which was prepared from the aldehyde (12) and the organostannane (16).
- Nemoto, Hideo,Wu, Xiao-Ming,Kurobe, Hiroshi,Minemura, Kayoko,Ihara, Masataka,at. al.
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p. 1185 - 1190
(2007/10/02)
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- A MODIFIED SYNTHESIS OF THE (+)-8α-PHENYLSULPHONYL-DES-AB-CHOLESTANE VIA AN INTRAMOLECULAR NUCLEOPHILIC ATTACK TO EPOXIDE - A TOTAL SYNTHESIS OF VITAMIN D3
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An intramolecular alkylation of the phenylsulphonyl epoxide (6), which was readily obtained from the alsehyde (5), gave a separable mixture of the alcohols (7a) and (8a).The alcohol (8a) was then dehydrated via the corresponding mesylate (8b) to afford th
- Nemoto, Hideo,Kurobe, Hiroshi,Fukumoto, Keiichiro,Kametani, Tetsuji
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p. 567 - 569
(2007/10/02)
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- 1α-HYDROXY PREVITAMIN D3 AND ITS SELECTIVE FORMATION FROM 1-KETO PREVITAMIN D3
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An efficient method for the preparation of crystalline 1α-hydroxy previtamin D3 is described.Also the stereoselective reduction of 1-keto previtamin 9 is discussed; it was observed that with aluminium hydride 7 is the most abundant product.This stands in contrast with previously reported LiAlH4 and NaBH4 mediated reductions.
- Vanmaele, L. J.,Clercq, P. J. De,Vandewalle, M.,Halkes, S. J.,Overbeek, W. R. M.
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p. 1179 - 1182
(2007/10/02)
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- A FACILE RING-OPENING REACTION OF CYCLOBUTENES: APPLICATION TO A SYNTHESIS OF VITAMIN D3
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The exraordinary accelerating effects of arylsulfinyl, arylsulfonyl, and diphenylphosphinoyl carbanion substituents for cyclobutene ring-opening reaction of bicyclo-oct-1(6)-ene derivatives are described.The scope and limitation of this new type of
- Nemoto, Hideo,Suzuki, Koji,Tsubuki, Masayoshi,Minemura, Kayoko,Fukumoto, Keiichiro,et al.
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p. 1123 - 1132
(2007/10/02)
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- Vitamin D glycosides and a method of use
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A synthetic compound which is biologically active in maintaining calcium and phosphorous metabolism in animals, of the formula I STR1 wherein the double bond between positions C-22 and C-23 is single or double; R2 is hydrogen, CH3 or CH2 CH3 ; X is selected from the group consisting of hydrogen and --OR1, where R1 is hydrogen or a straight or branched chain glycosidic residue containing 1-20 glycosidic units per residue; with the proviso that at least one of the R1 is a glycosidic residue.
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- Isotopically labeled vitamin D derivatives and processes for preparing same
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This invention relates to isotopically labeled vitamin D compounds, including radiolabeled vitamin D compounds of high specific activity, methods for their preparation, and novel intermediates in their synthesis. The radiolabeled vitamin D compounds are characterized by high specific activity (up to 160 Ci/mmol) with the process providing a facile and convenient method for synthesizing such compounds.
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- Calciferol and its Relatives. Part 27. A Synthesis of 1α-Hydroxyvitamin D3 by way of 1α-Hydroxytachysterol3
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A new synthesis of 1α-hydroxyvitamin D3 is described.The bis-t-butyldimethylsilyl ether (17) of (3S,5R)-3,5-dihydroxy-2-methylcyclohex-1-enecarbaldehyde and 8-p-tolylsulphonylmethyl-des-AB-cholest-8-ene (4) were combined to give mixed benzoyloxysulphones which, on reductive elimination with sodium amalgam, gave the corresponding bis-ether of 1α-hydroxytachysterol3.This was isomerised photochemically to the bis-ether of 1α-hydroxyprecalciferol3, and then thermally to give the bis-ether of 1α-hydroxyvitamin D3.Removal of protecting groups gave 1α-hydroxyvitamin D3 (21) in 62percent yield from the sulphone (4), or 12.8percent overall from cholesterol.
- Kocienski, Philip J.,Lythgoe, Basil
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p. 1400 - 1404
(2007/10/02)
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