Claims
- 1. A process for the preparation of vitamin D compounds having the general structure: ##STR8## where X and Y, which may be the same or different, are selected from the group consisting of hydrogen and a hydroxy-protecting group, and where R is selected from the group consisting of alkyl, fluoro-substituted alkyl, hydroxy-substituted alkyl, hydroxy and fluoro-substituted alkyl, hydroxy-protected hydroxy-substituted alkyl and hydroxy-protected hydroxy- and fluoro-substituted alkyl, which comprises treating a vitamin D-22-tosylate derivative, of the general structure: ##STR9## where X and Y are selected from the group consisting of hydrogen and hydroxy-protecting groups, with an alkylphenylsulfone derivative of the general structure:
- Ph--SO.sub.2 --CH.sub.2 --R
- wherein R is selected from the group consisting of alkyl, fluoro-substituted alkyl, hydroxy-substituted alkyl, and hydroxy- and fluoro-substituted alkyl, any hydroxy group present being preferably derivatized by hydroxy-protecting groups, thereby obtaining a side chain sulfone adduct, having the following general structure: ##STR10## wherein X, Y and R represent the groupings defined above, and reductively desulfonating said side chain sulfone adduct so as to obtain the corresponding vitamin D compound, and, optionally removing the hydroxy-protecting groups present.
- 2. The method of claim 1 where X and Y are hydroxy-protecting groups.
- 3. The method of claim 2 where R is 4-methyl-4-hydroxypentyl in hydroxy-protected form.
- 4. The method of claim 2 where R is 5-methyl-5-hydroxyhexyl in hydroxy-protected form.
- 5. Compounds having the structure: ##STR11## wherein X and Y, which may be the same or different, are selected from the group consisting of hydrogen and a hydroxy-protecting group, and where R is selected from the group consisting of 4-methyl-4-hydroxy-pentyl, 5-methyl-5-hydroxy-hexyl, and their corresponding hydroxy-protected forms.
- 6. The compounds of claim 5 where X and Y are hydrogen.
- 7. The compounds of claim 5 where X and Y are hydroxy-protecting groups.
- 8. The compounds of claim 5 where R is 4-methyl-4-hydroxypentyl.
- 9. The compounds of claim 5 where R is 4-methyl-4-hydroxypentyl in its hydroxy-protected form.
- 10. The compounds of claim 5 where R is 5-methyl-5-hydroxyhexyl.
- 11. The compounds of claim 5 where R is 5-methyl-5-hydroxyhexyl in its hydroxy-protected form.
- 12. Compounds having the structure: ##STR12## where X, Y and Z, which may be the same or different, selected from the group consisting of hydrogen and a hydroxy-protecting group, and where n is 3 or 4.
- 13. The compounds of claim 12 where X, Y and Z are hydroxy-protecting groups.
- 14. The compounds of claim 13 where X, Y and Z are alkylsilyl groups.
- 15. The compounds of claim 12 where X, Y and Z are hydrogen.
- 16. A pharmaceutical composition containing a compound as claimed in claim 12 together with a pharmaceutically acceptable excipient.
- 17. A pharmaceutical composition as claimed in claim 16 where the compound is 24-dihomo-1.alpha.,25-dihydroxyvitamin D.sub.3.
- 18. A pharmaceutical composition as claimed in claim 16 where the compound is 24-trihomo-1.alpha.,25-dihydroxyvitamin D.sub.3.
- 19. A method for inducing and enhancing cell differentiation in malignant cells which comprises exposing said cells to at least one of the compounds claimed in claim 12, in an amount sufficient to induce cell differentiation.
- 20. The method as claimed in claim 19, where the compound is 24-dihomo-1.alpha.,25-dihydroxyvitamin D.sub.3.
- 21. The method as claimed in claim 19 where the compound is 24-trihomo-1.alpha.,25-dihydroxyvitamin D.sub.3.
- 22. A method for treating neoplastic diseases which comprises administering to a subject having a neoplastic disease an effective amount of at least one of the compounds of claim 12.
- 23. The method of claim 22 where the compound administered is 24-dihomo-1.alpha.,25-dihydroxyvitamin D.sub.3.
- 24. The method of claim 22 where the compound administered is 24-trihomo-1.alpha.,25-dihydroxyvitamin D.sub.3.
- 25. 24-dihomo-1.alpha.,25-dihydroxyvitamin D.sub.3.
- 26. 24-trihomo-1.alpha.,25-dihydroxyvitamin D.sub.3.
Government Interests
This invention was made in the course of work supported by grants or awards from the Department of Health and Human Services. The Government has certain rights in this invention.
US Referenced Citations (3)
Number |
Name |
Date |
Kind |
4717721 |
DeLuca et al. |
Jan 1988 |
|
4758382 |
Sterling et al. |
Jul 1988 |
|
4804502 |
Baggiolini et al. |
Feb 1989 |
|
Non-Patent Literature Citations (2)
Entry |
Chemical Abstracts; vol. 109 (1988), #55060u; Kutner et al. |
1,2,5-Dihydroxyvitamin D.sub.3 Analogs and Cell Differentiation; University of Wisconsin-Madison, Dept. of Biochemistry (1989); DeLuca et al. |