- Photoisomerization of alfa calcidol by a sensitized quantum chain reaction
-
The production of vitamin D3 is a pharmaceutically relevant process, producing high added-value products. Precursors are extracts from vegetal origin but bearing mainly an E geometry in the 5,6 double bond. The synthesis of vitamin D3 (5-E-α-calcidol) wit
- Estruch, Gast?n A.,Aramendía, Pedro F.
-
-
Read Online
- Improved preparation method of alfacalcidol
-
The invention discloses an improved preparation method of alfacalcidol. The preparation method is characterized by comprising the following steps: starting from 1 alpha-OH-3,5-cyclized vitamin D3, directly carrying out ring-opening hydrolysis without an acetate intermediate to obtain alfacalcidol and a trans-isomer thereof, carrying out a Diels-Alder reaction, selectively reacting with the trans-isomer, and carrying out column chromatography separation or methyl formate recrystallization to obtain a pure alfacalcidol product. The method is simple and convenient to operate, mild in reaction condition and high in total yield, and is suitable for large-scale synthesis of products.
- -
-
Paragraph 0028-0030; 0032-0034; 0036-0038
(2020/05/08)
-
- Refining method for alfacalcidol
-
The invention provides a refining method for alfacalcidol. The refining method comprises the following steps: firstly, converting a crude product of alfacalcidol into alfacalcidol sulphate; forming sodium alfacalcidol sulphate; re-crystallizing sodium alfacalcidol sulphate and then degreasing. The reaction equation is as follows. According to the refining method for alfacalcidol provided by the invention, the crude product of alfacalcidol is firstly converted into alfacalcidol sulphate, and then the sodium alfacalcidol sulphate is formed, and the sodium alfacalcidol sulphate is re-crystallizedand then is degreased; the refining efficiency is high, the cost is low and the production stability is high; the refining method can meet the requirement for volume production and has a bright application prospect.
- -
-
Paragraph 0023; 0024; 0025; 0026
(2019/04/13)
-
- Method for preparing high-purity 1 alpha-hydroxyvitamin D3
-
The invention discloses a method for preparing high-purity 1 alpha-hydroxyvitamin D3. The method comprises the following steps of (1) carrying out esterification; (2) carrying out cyclization; (3) carrying out oxidization; (4) carrying out ring opening; (5) carrying out photochemical isomerisation; (6) utilizing molecular sieve zeolite to carry out chiral purification and treatment on crude 1 alpha-hydroxyvitamin D3, and finally, carrying out recrystallization with an ethyl acetate-n-hexane system to obtain the high-purity 1 alpha-hydroxyvitamin D3. According to the method, by using a liposoluble solvent to replace pyridine and using an organic alkaline catalyst, under the condition with equivalent yield, the reaction temperature is changed from low temperature to room temperature, the reaction time is shortened, the pyridine with large pungent smell is avoided from using, and thus the economic practicability of the technology is greatly improved.
- -
-
Paragraph 0025; 0026
(2018/03/01)
-
- A modified synthesis of the antiosteoporosis drug alfacalcidol via a key photochemical transformation of 1α-5,6-Trans-Vitamin D3
-
Alfacalcidol (1α-hydroxyvitamin D3) is an important clinical drug for the treatment of osteoporosis. Its practical synthesis has been intensively pursued across academia. The difficulties of separating 5,6-cis and 5,6-trans isomers in the current process was avoided by photochemical transformation of the 5,6-trans isomer into the 5,6-cis isomer. Employing vitamin D3 as a starting material, alfacalcidol was obtained by a five-step reaction sequence of esterification, cyclization, oxidation, solvolysis ring-opening, and subsequent photochemical reaction. The overall yield has been greatly improved from 17% to 31%. Georg Thieme Verlag Stuttgart New York.
- Ding, Junyuan,Guo, Xianghai,Zeng, Zhouliangzi,Liu, Ningzhi
-
p. 2606 - 2608
(2013/12/04)
-
- Continuous-flow synthesis of activated vitamin D3 and its analogues
-
An efficient, two-stage, continuous-flow synthesis of 1α,25-(OH) 2-vitamin D3 (activated vitamin D3) and its analogues was achieved. The developed method afforded the desired products in satisfactory yields using a high-intensity and economical light source, i.e., a high-pressure mercury lamp. In addition, our method required neither intermediate purification nor high-dilution conditions. The Royal Society of Chemistry 2012.
- Fuse, Shinichiro,Mifune, Yuto,Tanabe, Nobutake,Takahashi, Takashi
-
experimental part
p. 5205 - 5211
(2012/08/08)
-
- Pd-catalyzed carbocyclization-negishi cross-coupling cascade: A novel approach to 1α,25-dihydroxyvitamin D3 and analogues
-
(Chemical Equation Presented) A mild palladium-catalyzed cascade has been used for the synthesis of the hormone 1α,25-dihydroxyvitamin D3 (calcitriol, 1a) and its analogues 1b and 1c. This one-pot process involves two consecutive transformations at room temperature: An initial palladium-catalyzed 6-exo-cyclocarbopalladation of vinyl triflates followed by a Negishi cross-coupling reaction with an alkenyl zinc. This novel strategy opens new possibilities for the preparation of a variety of new vitamin D analogues of therapeutic potential, particularly with modifications at the triene and/or ring-A.
- Gomez-Reino, Clara,Vitale, Cristian,Maestro, Miguel,Mourino, Antonio
-
p. 5885 - 5887
(2007/10/03)
-
- Treatment of inflammatory bowel disease with vitamin D compounds
-
A method of treating inflammatory bowel disease, particularly ulcerative colitis and Crohn's disease, is disclosed. The method involves administering a vitamin D compound in an amount effective to treat the disease. The administration of a vitamin D compound also prevents the development of or delays the onset of inflammatory bowel disease in susceptible individuals.
- -
-
-
- VITAMIN D DERIVATIVES AND PROCESS FOR PRODUCING THE SAME
-
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.
- -
-
-
- Synthesis and pharmacokinetics of 1α-hydroxyvitamin D3 tritiated at 22 and 23 positions showing high specific radioactivity
-
A novel synthesis of a radioactive compound of 1α-hydroxyvitamin D3 (1αOHD3) (1) and its pharmacokinetics are described. Radioactive 1αOHD3 tritiated at 22 and 23 positions ([22,23-3H4]1αOHD3) (5) was prepared via key reactions of the reduction of acetylenic side chain in the ketone (12) with tritium gas in the presence of palladium-charcoal and the subsequent Wittig reaction with the A-ring synthon (16). [22,23-3H4]1αOHD3 (5) showed high specific radioactivity (111.5 Ci/mmol) and was used successfully in pharmacokinetics studies with rats. In the pharmacokinetics studies, the plasma concentration level of the active form of vitamin D3, 1α,25- dihydroxyvitamin D3 [1α,25(OH)2D3], after oral or intravenous administration of [22,23-3H4]1αOHD3 (5), showed longer half-life, lower maximum concentration, and lower area under the curve than those after treatment of 1α,25(OH)2D3 tritiated at 26 and 27 positions (4). These results might suggest a beneficial therapeutic utility of 1αOHD1 (1) over the treatment of 1α,25(OH)2D3 (2).
- Kawase, Akira,Ichikawa, Fumihiko,Koike, Nobuo,Kamachi, Shinichi,Stumpf, Walter E.,Nishii, Yasuho,Kubodera, Noboru
-
p. 215 - 219
(2007/10/03)
-
- 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
-
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
-
p. 1431 - 1436
(2007/10/03)
-
- A General Synthetic Route to A-Ring Hydroxylated Vitamin D Analogs from Pentoses
-
The enyne needed for coupling to a CD-ring fragment, namely, 3S,5R-oct-1-en-7-yne-3,5-diol, in the Trost-Dumas carbopalladation route to 1α,25-dihydroxyvitamin D3 was synthesized from D-xylose in 13 steps and 21percent yield.
- Moriarty, Robert M.,Kim, Joonggon,Brumer, Harry
-
-
- Palladium catalyzed alkylative cyclization useful in synthesis of vitamin D and analogues
-
An alkylative cycloaddition method is provided that is particularly useful for the synthesis of many of the Vitamin D analogues with differing side chains. Thus, a preferred synthesis is of Vitamin D analogues having a side chain R1 where a substantially geometrically pure first precursor having the structure STR1 and a second precursor are provided, the second precursor being a 1,7 enyne. These precursors are reacted in the presence of a palladium catalyst to form compounds having the structure STR2 where R2 hydrogen, hydroxyl, lower alkoxy, fluorine, or a protecting group, and R3 is hydrogen, hydroxyl, lower alkoxy, fluorine, or a protecting group.
- -
-
-
- Steroid compounds
-
Steroid compounds of the following general formulas (I), (II) and (III) are provided: STR1 In the above formulas, R1 and R2 each is a hydrogen atom or a hydroxyl-protecting group, R is a group of the formula --CH2 --X (in which X is a substituent such as a hydroxyl group), a carboxyl group or a protected carboxyl group, A1 is an aryl group, a lower alkyl group or an aralkyl group, and Z1, Z2, Z3 and Z4 each is a hydrogen atom, a hydroxyl group or a protected hydroxyl group. The above steroid compounds are useful as intermediates for the synthesis of vitamin D3 derivatives having a hydroxyl group at the 1α-position.
- -
-
-
- New strategies for the synthesis of vitamin D metabolites via Pd-catalyzed reactions
-
The invention of new palladium-catalyzed reactions offers new insights into synthetic strategies directed toward the vitamin D system. The palladium-catalyzed cycloisomerization of 1,6- and 1,7-enynes to dialkylidenecycloalkanes permits a lynchpin approach to the A ring of vitamin Ds. Using the thioacetal of formaldehyde, the proper subunits containing the olefin and the acetylene were attached. Pd(2+) effected cycloisomerization to an A ring subunit. A more effective strategy evolved from the evolution of a Pd-catalyzed alkylative cyclization of enynes. Whereas prior work established the feasibility of this process for 1,6-enynes, model studies reported herein demonstrate the feasibility of its extension to 1,7-enynes. This reaction permits the creation of a new concept for vitamin D synthesis wherein A ring formation is concomitant with its attachment to an appropriate CD fragment. An asymmetric synthesis of the requistite 1,7-enyne required six steps. Bromomethylenation of Grundmann's ketone and its side chain hydroxylated derivative proceeded with excellent geometrical selectivity (>30:1) using the Wittig reaction. A Pd catalyst generated from (dba)3Pd2·CHCl3 and triphenylphosphine stitched together these two units in a single step resulting in syntheses of alphacalcidiol and calcitriol.
- Trost, Barry M.,Dumas, Jacques,Villa, Marco
-
p. 9836 - 9845
(2007/10/02)
-
- Method for treating psoriasis by externally administering to a patient a pharmaceutical composition containing active-type vitamin D
-
A process for treating psoriasis by externally applying to the skin of a warm-blooded animal a composition comprising: (A) a pharmaceutically effective amount of an active-type vitamin D3, (B) a substantially water-free carrier containing the active-type vitamin D3 dissolved or uniformly dispersed therein, and (C) a solvent selected from fatty acid esters, higher alcohols with 10 or more carbons and propylene carbonate.
- -
-
-
- A Stereoselective Synthesis of 1α-Hydroxyvitamin D3
-
A stereoslelective synthesis of 1α-hydroxyvitamin D3 (16) was achieved through the solvolysis of the 3,5-cyclovitamin D3 (14) which was prepared form (-)-(1R,3S,5S)-3-methoxymethoxy-2-methylenebicyclohexanecarbaldehyde (13) and 8-bromomethylenedes-AB-cholestane (1).
- Nemoto, Hideo,Kimura, Toshihiko,Kurobe, Hiroshi,Fukumoto, Keiichiro,Kametani, Tetsuji
-
p. 1777 - 1780
(2007/10/02)
-
- A STEREOSELECTIVE SYNTHESIS OF 1 α-HYDROXY-VITAMIN D3
-
A stereoselective synthesis of 1 α-hydroxy-vitamin D3 was achieved through the solvolysis of the 3,5-cyclovitamin D3 which was prepared from (-)-(3S,5R) -2-methylene-3-methoxymethyloxybicyclohexanecarboxaldehyde and the des-AB-8-bromomethylenecholestane.
- Nemoto, Hideo,Kimura, Toshihiko,Kurobe, Hiroshi,Fukumoto, Keiichiro,Kametani, Tetsuji
-
p. 1131 - 1132
(2007/10/02)
-
- Method of preparing 1 α-hydroxyvitamin D and 1 α-hydroxyprevitamin D compounds, and adducts of a previtamin D or tachysterol compound with a suitable dienophile
-
The invention relates to a method of preparing 1 α-hydroxyvitamin D or 1 α-hydroxy-previtamin D compounds by hydroxylating the 1 α-position of an adduct of a previtamin D compound with a suitable dienophile, in which adduct optionally present hydroxy group or hydroxy groups is or are protected, if desired, and after removal of the protecting group or groups, isolating the 1 α-hydroxyvitamin D or 1 α-hydroxy-previtamin D compound. The invention also relates to 1 α-hydroxy-previtamin D compounds. The invention further relates to an adduct of a previtamin D or tachysterol compound with a dienophile of the general formula STR1 in which A' and B' are equal and represent methoxy groups or ethoxy groups, or in which A' and B' together constitute a phenylimino or o-phenylene group.
- -
-
-
- Method for preparing 1α-hydroxyvitamin D compounds
-
The invention relates to a process for separating 1α-hydroxyvitamin D compounds from their corresponding 1α-hydroxy-5,6-trans isomers in a mixture thereof by treating the mixture with a dienophile and then separating the resulting dienophil-adduct of the 1α-hydroxy-5,6-trans vitamin D isomer from the unreacted 1α-hydroxyvitamin D compound.
- -
-
-
- Method for preparing 1-hydroxyvitamin D compounds
-
The invention relates to a process for preparing 1-hydroxyvitamin D compounds by acid-catalyzed solvolysis of the corresponding 1-hydroxy-3,5-cyclovitamin D compound in an organic solvent medium whereby the free, non-acylated, 5,6-cis and 5,6-trans-1-hydroxylated vitamin D compounds are obtained in admixture.
- -
-
-
- Process for the preparation of active-type vitamin D3 compounds
-
The present invention relates to a novel process for the preparation of active-type vitamin D3 compounds and their intermediates. In accordance with the present invention, a large amount of an active-type vitamin D3 compounds, for example 1α-hydroxycholecalciferol, 1α,25-dihydroxycholecalciferol and the like, is efficiently prepared with high industrial advantages by a novel processes, which comprises (i) reacting hydroxycholesta-5-enes having the hydroxyl groups protected with lower alkoxycarbonyl group as a starting material with allylic brominating agent and dehydrobrominating agent to prepare the corresponding hydroxycholesta-5,7-dienes, (ii) exposing the hydroxycholesta-5,7-dienes to ultraviolet irradiation or to a combination of the irradiation with thermal isomerization to obtain a mixture of the unreacted hydroxycholesta-5,7-dienes and previtamin D3 compounds or a mixture of the unreacted hydroxycholesta-5,7-dienes and the protected active-type vitamin D3 compounds, (iii) separating the mixture into the unreacted hydroxycholesta-5,7-dienes and previtamin D3 compounds or the protected active-type vitamin D3 compounds, (iv) recycling the unreacted hydroxycholesta-5,7-dienes as reuse and (v) thermally isomerizing the remaining compounds and/or splitting off the protective groups. The process for the preparation of active-type vitamin D3 compounds, in the present invention, is of very high industrial value, capable of carrying out by simple operation and adaptable to large scale commercial production.
- -
-
-
- Process for preparing 1-hydroxylated vitamin D compounds from 5,6-trans-vitamin D compounds
-
A method for preparing 1α-hydroxylated vitamin D compounds from 5,6-trans-vitamin D compounds which comprises allylically oxidizing a 5,6-trans-vitamin D compound, subjecting the oxidation product to actinic radiation in the presence of a photosensitizing agent and recovering the 1α-hydroxylated compound. 1α-hydroxylation is recognized as being essential to impart biological activity to vitamin D compounds and their derivatives. The present invention provides an efficient method for maximizing the yield of 1α-hydroxylated vitamin D compounds.
- -
-
-
- Process for preparing 1α-hydroxylated compounds
-
An improved method for the preparation of 1α-hydroxylated vitamin D compounds involving directly introducing an oxygen function at carbon 1 of the vitamin D molecule or precursors or derivatives thereof, wherein the 1α-hydroxycyclovitamin D intermediate is solvolyzed directly, without first converting the 1-hydroxy group to a 1-O-acyl function as a protective measure.
- -
-
-
- Calciferol and its Relatives. Part 28. A Stereoselective Synthesis of 1α-Hydroxyprecalciferol3 from 8-Hydroxymethyl-des-AB-cholest-8-ene
-
8-p-Tolylsulphonylmethyl-des-AB-cholest-8-ene (1) and methyl (3S,5R)-3,5-bis-t-butyldimethylsilyloxy-2-methylcyclohex-1-enecarboxylate (2) were combined to give a 6-oxo-7-sulphone from which 1α,3β-diacetoxy-9,10-seco-cholesta-5(10),8-diene-6-yne (4) was obtained.Semihydrogenation and deacetylation gave 1α-hydroxyprecalciferol3 (6), which was converted by thermal isomerization into 1α-hydroxyvitamin D3 (7).
- Lithgoe, Basil,Waterhouse, Ian
-
p. 1405 - 1406
(2007/10/02)
-
- Calciferol and its Relatives. Part 27. A Synthesis of 1α-Hydroxyvitamin D3 by way of 1α-Hydroxytachysterol3
-
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
-
p. 1400 - 1404
(2007/10/02)
-
- Process for preparing 1α-hydroxylated compounds
-
A method for directly introducing an oxygen function at carbon 1 of the vitamin D molecule or precursors of derivatives thereof which comprises subjecting such molecules to allylic oxidation utilizing selenium dioxide as the oxidizing agent.
- -
-
-
- Direct C(1) Hydroxylation of Vitamin D3 and Related Compounds
-
A direct synthesis of C(1) hydroxylated vitamin D analogues from the corresponding vitamin D precursors has been developed.Allylic oxidation of 3,5-cyclovitamin D derivatives, readily obtained from the buffered solvolysis of vitamin D tosylates, with selenium dioxide yields 1α-hydroxylated 3,5-cyclovitamin D compounds which are smoothly converted to the desired 1α-hydroxyvitamin D derivatives by acid-catalyzed cycloreversion.Application of this scheme to vitamin D3 (1a), 25-hydroxyvitamin D3 (1b), and vitamin D2 (1c) affords the 1α-hydroxy products in ca.20 percent overall yield.
- Paaren, Herbert E.,DeLuca, Hector F.,Schnoes, Heinrich K.
-
p. 3253 - 3258
(2007/10/02)
-
- Process for preparing 1α-hydroxylated compounds
-
A method for directly introducing an oxygen function at carbon 1 of the vitamin D molecule or precursors or derivatives thereof which comprises subjecting such molecules to allylic oxidation utilizing selenium dioxide as the oxidizing agent.
- -
-
-
- Process for preparing 1α-hydroxyvitamin D compounds from 1α-hydroxy-3,5-cyclovitamin D compounds
-
A method for preparing 1α-hydroxyvitamin D compounds from 1α-hydroxy-3,5-cyclovitamin D compounds which comprises solvolyzing the 3,5-cyclovitamin D compound, exposing the solvolysis reaction products to actinic radiation in the presence of a photosensitizing agent and recovering the 1α-hydroxylated vitamin D compounds. 1α-hydroxylation is recognized as being essential to impart biological activity to vitamin D compounds and their derivatives. The present invention provides an efficient method for maximizing the yield of 1α-hydroxylated vitamin D compounds.
- -
-
-
