Process for preparing vitamin D.sub.2 compounds and the corresponding 1 .alpha.-hydroxylated derivatives
First Claim
1. A method for preparing vitamin D compounds having the formulawhere R3 can have either the R or S configuration and wherein n is an integer having a value of from 1 to 5, X1 is selected from hydrogen or a hydroxy protecting group, R3 is selected from an alkyl of 1 to 6 carbon atoms, hydroxy, protected hydroxy, hydrogen or fluorine, and where R1 and R2, which may be the same or different, are each selected from an alkyl of 1 to 6 carbon atoms or an aryl, said aryl selected from the group consisting of a phenyl or a substituted phenyl, which comprises condensing in the presence of a strong base in an organic solvent at a temperature below 0°
- C. a steroidal aldehyde of the formula ##STR6## wherein X1 is as defined above, with an arylsulfone of the formula
space="preserve" listing-type="equation">ArSO.sub.2 CH.sub.2 Rwherein Ar is selected from the group consisting of a phenyl and a tolyl, and R is selected from the group consisting of an alkyl of from 1 to 25 carbon atoms, hydroxylated alkyl, hydroxy-protected hydroxylated alkyl, fluoro-substituted alkyl, fluoro-substituted hydroxylated alkyl and fluoro-substituted hydroxy-protected alkyl, whereby a hydroxy-sulfonyl adduct of the formula ##STR7## is obtained, wherein Ar, R and X1 are as defined above, reducing said adduct with a metal amalgum reagent in an organic solvent at a temperature of from about 0°
C. to about ambient to obtain an intermediate of the formula ##STR8## wherein R and X1 are as defined above, and converting said intermediate to obtain the desired vitamin D compound.
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Abstract
This invention relates to hydroxylated derivatives of vitamin D2 and a process for preparing such compounds. In particular, a process for preparing the 24-epimer of vitamin D2 and the corresponding 1α-hydroxylated derivative thereof is disclosed. The vitamin D2 derivatives would find application in the treatment of or prophylaxsis for various disease states characterized by calcium and phosphorous imbalances.
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Citations
13 Claims
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1. A method for preparing vitamin D compounds having the formula
where R3 can have either the R or S configuration and wherein n is an integer having a value of from 1 to 5, X1 is selected from hydrogen or a hydroxy protecting group, R3 is selected from an alkyl of 1 to 6 carbon atoms, hydroxy, protected hydroxy, hydrogen or fluorine, and where R1 and R2, which may be the same or different, are each selected from an alkyl of 1 to 6 carbon atoms or an aryl, said aryl selected from the group consisting of a phenyl or a substituted phenyl, which comprises condensing in the presence of a strong base in an organic solvent at a temperature below 0° - C. a steroidal aldehyde of the formula ##STR6## wherein X1 is as defined above, with an arylsulfone of the formula
space="preserve" listing-type="equation">ArSO.sub.2 CH.sub.2 Rwherein Ar is selected from the group consisting of a phenyl and a tolyl, and R is selected from the group consisting of an alkyl of from 1 to 25 carbon atoms, hydroxylated alkyl, hydroxy-protected hydroxylated alkyl, fluoro-substituted alkyl, fluoro-substituted hydroxylated alkyl and fluoro-substituted hydroxy-protected alkyl, whereby a hydroxy-sulfonyl adduct of the formula ##STR7## is obtained, wherein Ar, R and X1 are as defined above, reducing said adduct with a metal amalgum reagent in an organic solvent at a temperature of from about 0°
C. to about ambient to obtain an intermediate of the formula ##STR8## wherein R and X1 are as defined above, and converting said intermediate to obtain the desired vitamin D compound. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 13)
- C. a steroidal aldehyde of the formula ##STR6## wherein X1 is as defined above, with an arylsulfone of the formula
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9. A method for preparing 24-epi-vitamin D2 having the formula ##STR9## which comprises condensing in the presence of a strong base in an organic solvent at a temperature below 0°
- C. a steroidal aldehyde of the formula ##STR10## with a phenylsulfone of the formula ##STR11## whereby a hydroxy-sulfonyl adduct of the formula ##STR12## is obtained, reducing said adduct with a metal amalgum reagent in an organic solvent at a temperature of from about 0°
C. to about ambient to obtain an intermediate of the formula ##STR13## and converting said intermediate to obtain 24-epi-vitamin D2. - View Dependent Claims (10)
- C. a steroidal aldehyde of the formula ##STR10## with a phenylsulfone of the formula ##STR11## whereby a hydroxy-sulfonyl adduct of the formula ##STR12## is obtained, reducing said adduct with a metal amalgum reagent in an organic solvent at a temperature of from about 0°
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11. A method for preparing vitamin D2 having the formula ##STR14## which comprises condensing in the presence of a strong base in an organic solvent at a temperature below 0°
- C. a steroidal aldehyde of the formula ##STR15## with a phenyl sulfone of the formula ##STR16## whereby a hydroxy-sulfonyl adduct of the formula ##STR17## is obtained, reducing said adduct with a metal amalgum reagent in an organic solvent at a temperature of from about 0°
C. to about ambient to obtain an intermediate of the formula ##STR18## and converting said intermediate to obtain vitamin D2. - View Dependent Claims (12)
- C. a steroidal aldehyde of the formula ##STR15## with a phenyl sulfone of the formula ##STR16## whereby a hydroxy-sulfonyl adduct of the formula ##STR17## is obtained, reducing said adduct with a metal amalgum reagent in an organic solvent at a temperature of from about 0°
Specification