Wisconsin Alumni Research Foundation

Agnieszka Flores

Hector Floyd Deluca

Hazel Holden

James Thoden

Lori A Plum

Margaret Clagett-Dame

Pawel Grzywacz

James B Thoden

Hector F Deluca

Hazel M Holden

Disclosed are methods of purifying the compound (22E)-(24R)-2-methylene-22-dehydro-1&#x3b1;,24,25-trihydroxy-19-nor-vitamin Dto obtain the compound in crystalline form. The methods typically include the steps of dissolving (22E)-(24R)-2-methylene-22-dehydro-1&#x3b1;,24,25-trihydroxy-19-nor-vitamin Din a solvent comprising ethyl acetate and hexane to form a solution, allowing crystals of (22E)-(24R)-2-methylene-22-dehydro-1&#x3b1;,24,25-trihydroxy-19-nor-vitamin Dto form and precipitate from the solution, and recovering the crystals of (22E)-(24R)-2-methylene-22-dehydro-1&#x3b1;,24,25-trihydroxy-19-nor-vitamin Dfrom the solution.

Procedure for crystallization of (22E)-(24R)-2-methylene-22-dehydro-1&#x3b1;,24-25-trihydroxy-19-nor-vitamin D

Disclosed are 1&#x3b1;,25-dihydroxy-24,24-difluoro-2-methylene-19-nor-vitamin D analogs and their pharmaceutical uses. These new vitamin D analogs are 19-nor-vitamin D analogs having two fluorine atom substitutions at the 24 position (C-24) in the side chain and optionally having a 2-methylene substituent.

(20S)-1-&#x3b1;,25-dihydroxy-24,24-difluoro-19-nor-vitamin Danalogs and their pharmaceutical uses

Disclosed are methods of purifying the compound (20R,22R)-2-methylene-19-nor-22-methyl-1&#x3b1;,25-dihydroxyvitamin Dto obtain the compound in crystalline form. The methods typically include the steps of dissolving a product containing the compound in a solvent comprising hexane and 2-propanol, cooling the solvent and dissolved product below ambient temperature for a sufficient amount of time to form a precipitate of crystals, and recovering the crystals. Certain diol precursors formed during the synthesis of the compound and its diasteromers also may be obtained in crystalline form using ethyl acetate as a solvent.

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Disclosed are methods of purifying the compound (20R)-19-nor-24-difluoro-1&#x3b1;,25-dihydroxyvitamin Dto obtain the compound in crystalline form. The methods typically include the steps of dissolving a product containing the compound in a solvent comprising hexane and 2-propanol, cooling the solvent and dissolved product below ambient temperature for a sufficient amount of time to form a precipitate of crystals, and recovering the crystals.

Disclosed are methods of purifying the compound (20R)-2-methylene-19-nor-24-difluoro-1&#x3b1;,25-dihydroxyvitamin Dto obtain the compound in crystalline form. The methods typically include the steps of dissolving a product containing the compound in a solvent comprising hexane and 2-propanol, cooling the solvent and dissolved product below ambient temperature for a sufficient amount of time to form a precipitate of crystals, and recovering the crystals.

Crystallization of (20R)-2-methylene-19-nor-24-difluoro-1&#x3b1;,25-dihydroxyvitamin D3

Disclosed are methods of purifying (20R) and (20S) analogs of 2-methylene-19-nor-22-dimethyl-1&#x3b1;,25-dihydroxyvitamin Dto obtain the (20R) and (20S) analogs in crystalline form. The method includes the steps of preparing a solvent of either diethyl ether or a mixture of 2-propanol and hexane, dissolving a product containing the (20R) and (20S) analog to be purified in the solvent, cooling the solvent and dissolved product below ambient temperature for a sufficient amount of time to form a precipitate of crystals, and recovering the crystals.

Compounds of formula I are provided where X, X, and Xare independently selected from H or hydroxy protecting groups. Such compounds may be used in preparing pharmaceutical compositions and are useful in treating a variety of biological conditions. 

Compounds of formula I are provided where X, Xand Xare independently selected from H or hydroxy protecting groups. Such compounds may be used in preparing pharmaceutical compositions and are useful in treating a variety of biological conditions. 

Growing community of inventors

Madison, WI, United States of America

Agnieszka Flores