- Calcipotriol intermediate compound and preparation method thereof
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The invention discloses a calcipotriol intermediate compound and a preparation method thereof. The structure of the compound is represented by general formula I shown in the description. In the general formula I, R1 is selected from a carbobenzoxy group (Cbz), a trimethylsilyl group (TMS), a triethylsilyl group (TES), a t-butyldimethylsilyl group (TBDMS), a triisopropylsilyl group (TIPS), a t-butyl-diphenylsilyl group (TBDPS) or a methoxymethyl group (MOM); and R2 is one of groups shown in the description.
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- Stereoselective synthesis of C24-hydroxylated vitamin D3 analogs: A practical and expeditius route to calcipotriol
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The synthesis of the clinically important drug calcipotriol (2, MC903) is described as an example of a new and efficient approach to C24-hydroxylated analogs and metabolites of vitamin D3 (1). The key step of the process is the generation of the C24 stereocenter by DAIB [(-)-3-exo-(dimethylamino)isoborneol]-catalyzed addition of the alkenylzinc derivative of alkyne 3 to cyclopropylcarboxaldehyde.
- Rumbo, Antonio,Perez-Garcia, Xenxo,Mourino, Antonio
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scheme or table
p. 68 - 70
(2011/11/14)
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- EPIMERIZATION BY STEREOSELECTIVE SYNTHESIS OF VITAMIN D ANALOGUES
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A method for epimerization process of C-24 ketones to desired C-24 alcohol by stereo selective reduction using chiral borane reducing agents in the presence of chiral auxillary such as (R)-2-methyl-CBS-oxazaborolidine for the preparation of calcipotriene intermedites and its process to calcipotriene.
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Page/Page column 11-12
(2009/06/27)
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- ISOMERISATION OF PHARMACEUTICAL INTERMEDIATES
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The present invention relates to an isomerisation method of vitamin D analogues, such as compounds useful for the synthesis of calcipotriol, and to and to the use of a flow- through photoreactor or continuous flow photoreactor reactor for making said vitamin D analogues. The present invention relates further to the use of intermediates produced with said method for making calcipotriol or calcipotriol monohydrate, or pharmaceutical formulations thereof.
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Page/Page column 20-21
(2008/06/13)
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- Method for preparing analogue of vitamin D
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A method for preparing analogues of C1,C24-dihydroxy-vitamin D is disclosed. Especially the method for preparing calcipotriol and tacalcitol from a starting material of Vitamin D2 is disclosed here. Calcipotriol (compound 1(a)) and tacalcitol (compound 1(b)) can be synthesized by the method of the present invention. Moreover, only nine steps are needed for the synthesis of calcipotriol using the method. Likewise, only ten steps are needed for the synthesis of tacalcitol by the present method. Hence, the present method, with less process steps and higher yields, represents an improvement over the conventional methods.
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Page/Page column 11
(2008/06/13)
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- PROCESS FOR PREPARATION OF A PHARMACEUTICAL GRADE CALCIPOTRIOL ANHYDROUS
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A process for the preparation of a pharmaceutical grade calcipotriol anhydrous, wherein a crude calcipotriol is dissolved in one or more solvents, of which at least one forms azeotropic system with water, and then: a) in the case the water and impurities content in the substance exceeds the admissible level, solvents are azeotropically evaporated under reduced pressure, resulting in a clear anhydrous oil , or (b) in the case the water content in the substance does not exceed the admissible level, the solution is allowed to crystallize the product, (c) product obtained in step (a) or (b) is crystallized at least once from anhydrous solvent or mixture of anhydrous solvents.
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Page/Page column 13-21
(2008/06/13)
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- STEREOSELECTIVE SYNTHESIS OF VITAMIN D ANALOGUES
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The present invention relates to intermediates useful for the synthesis of calcipotriol or calcipotriol monohydrate, to methods of producing said intermediates, and to methods of stereoselectively reducing said intermediates.
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Page/Page column 31
(2008/06/13)
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- Pharmaceutical composition
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A pharmaceutical composition for dermal use, wherein the composition has a first pharmacologically active component A consisting of at least one vitamin D or vitamin D analogue, and a second pharmacologically active component B consisting of at least one corticosteroid, wherein the difference between the maximum stability pH of said first component A and the maximum stability pH of said second component B is at least 1. The composition can also have at least one solvent component C, where component C is compounds of the general formula R3(OCH2C(R1)H)xOR2(I), wherein x is in the range of 2-60, R1in each of the x units independently is H or CH3, R2is straight chain or branched C1-20alkyl or benzoyl, and R3is H or phenylcarbonyloxy; di-(straight or branched)-C4-10alkyl esters of C4-C8dicarboxylic acids; straight or branched C12-18-alkyl benzoates; straight or branched C2-4-alkyl esters of straight or branched C10-18-alkanoic or -alkenoic acids; propylenglycol diesters with C8-14-alkanoic acids; and branched primary C18-24alkanols.
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- EPIMERIZATION OF ANALOGS OF VITAMIN D
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Provided is a method of general applicability of epimerizing a vitamin-D analog having an asymmetric allylic carbon atom at the C-24 position, which comprises the steps of: a) esterifying the hydroxyl group on the asymmetric allylic carbon atom at the 24 position with an esterifying agent, b) contacting a solution of the ester in a solvent with an epimerization-active solid, whereby the ester is epimerized, and c) hydrolysing the epimerized ester to obtain a mixture of C-24 epimers having a hydroxyl substituent on the asymmetric allylic carbon at position 24. The method is of particular utility in making calcipotriene.
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