Process for preparing 1.alpha.-hydroxylated compounds
AssigneeWisconsin Alumni Research Foundation
InventorsHector F. DeLuca, Heinrich K. Schnoes, David E. Hamer, Herbert E. Paaren
Life of this patent
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Abstract
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.
Claims65
A method for preparing 1.alpha.-hydroxylated vitamin D compounds having the general formulae ##STR17## wherein R is selected from the group consisting of substituted or unsubstituted, or saturated or unsaturated, or unsaturated and substituted cholesterol side chain groups, or where R may have the structure of the side chain of cholenic acid, or of homocholenic acid, or of 27-nor-25-ketocholesterol, or of 24-ketocholesterol,
- which comprises subjecting compounds having the general formula ##STR18## wherein R is defined as above and Z is selected from the group consisting of hydrogen, lower alkyl, lower acyl and aromatic acyl to allylic oxidation with selenium dioxide, recovering the corresponding 1.alpha.-hydroxy compound, acylating said 1.alpha.-hydroxy compound to form the 1.alpha.-O-acyl derivative, subjecting said derivative to acid catalyzed solvolysis, whereby the 5,6-cis and 5,6-trans-1.alpha.-O-acyl vitamin D compounds are produced in admixture, and removing the acyl groups from said compounds by hydrolysis or hydride reduction.
Compounds having the formula ##STR21## wherein Z is selected from the group consisting of hydrogen, lower alkyl, lower acyl, and aromatic acyl, and, each of R.sub.1, R.sub.2, and R.sub.3 are selected from the group consisting of hydrogen, hydroxyl, lower alkyl, O-lower alkyl, O-lower acyl, benzoate and fluorine and, except that when Z is hydrogen or methyl and both R.sub.1 and R.sub.3 are hydrogen, R.sub.2 cannot be hydrogen.
Compounds having the formula ##STR22## wherein Z is selected from the group consisting of hydrogen, lower alkyl, lower acyl, and aromatic acyl, each of R.sub.1, R.sub.2, and R.sub.3 are selected from the group consisting of hydrogen, hydroxyl, lower alkyl, O-lower alkyl, O-lower acyl, benzoate, and fluorine and R.sub.4 is selected from the group consisting of hydrogen and lower alkyl.
Compounds having the formula ##STR23## wherein Z is selected from the group consisting of hydrogen, lower alkyl, lower acyl, and aromatic acyl, each of R.sub.1, R.sub.2 and R.sub.3 are selected from the group consisting of hydrogen, hydroxyl, lower alkyl, O-lower alkyl, O-lower acyl, benzoate, and fluorine, and Y is selected from the group consisting of hydrogen, lower acyl and aromatic acyl.
Compounds having the formula ##STR24## wherein Z is selected from the group consisting of lower alkyl, lower acyl, aromatic acyl or hydrogen, each of R.sub.1, R.sub.2, and R.sub.3 are selected from the group consisting of hydrogen, hydroxyl, lower alkyl, O-lower alkyl, O-lower acyl, benzoate and fluorine, R.sub.4 is selected from the group consisting of hydrogen and lower alkyl, and Y is hydrogen, lower acyl or aromatic acyl.
Compounds having the formula ##STR25## wherein Z is hydrogen or lower alkyl, each of R.sub.1, R.sub.2, and R.sub.3 are selected from the group consisting of hydrogen, hydroxyl, lower alkyl, O-lower alkyl, O-lower acyl, benzoate and fluorine.
Compounds having the formula ##STR26## wherein Z is hydrogen or lower alkyl, each of R.sub.1, R.sub.2, and R.sub.3 are selected from the group consisting of hydrogen, hydroxyl, lower alkyl, O-lower alkyl, O-lower acyl, benzoate, and fluorine, and where R.sub.4 is hydrogen or lower alkyl.
1.alpha.-hydroxy-6-alkznoxy-3,5-cyclovitamin D.sub.3.
1.alpha.,25-dihydroxy-6-alkanoxy-3,5-cyclovitamin D.sub.3.
1.alpha.-hydroxy-6-methoxy-3,5-cyclovitamin D.sub.3.
1.alpha.-acetoxy-6-methoxy-3,5-cyclovitamin D.sub.3.
1.alpha.,25-dihydroxy-6-methoxy-3,5-cyclovitamin D.sub.3.
1.alpha.-acetoxy-25-hydroxy-6-methoxy-3,5-cyclovitamin D.sub.3.
1.alpha.,25-diacetoxy-6-methoxy-3,5-cyclovitamin D.sub.3.
1.alpha.,25-dihydroxy-6-alkanoxy-3,5-cyclovitamin D.sub.3.
1.alpha.-hydroxy-6-alkanoxy-3,5-cyclovitamin D.sub.2.
1.alpha.-hydroxy-6-methoxy-3,5-cyclovitamin D.sub.2.
1.alpha.-acetoxy-6-methoxy-3,5-cyclovitamin D.sub.2.
1.alpha.,25-dihydroxy-6-methoxy-3,5-cyclovitamin D.sub.2.
1.alpha.-acetoxy-25-hydroxy-6-methoxy-3,5-cyclovitamin D.sub.2.
1.alpha.,25-diacetoxy-6-methoxy-3,5-cyclovitamin D.sub.2.
1.alpha.,24,25-trihydroxy-6-alkanoxy-3,5-cyclovitamin D.sub.3.
1-oxo-6-alkanoxy-3,5-cyclovitamin D.sub.3.
1-oxo-25-hydroxy-6-alkanoxy-3,5-cyclovitamin D.sub.3.
1-oxo-24,25-dihydroxy-6-alkanoxy-3,5-cyclovitamin D.sub.3.
1-oxo-6-alkanoxy-3,5-cyclovitamin D.sub.2.
1-oxo-25-hydroxy-6-alkanoxy-3,5-cyclovitamin D.sub.2.
Dependencies are inferred from the claim text.