Vitamin D related compounds and processes for their preparation

• US 4,847,012 A
• Filed: 04/29/1988
• Issued: 07/11/1989
• Est. Priority Date: 04/29/1988
• Status: Expired due to Term

• Current Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Original Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Inventors: DeLuca, Hector F., Kutner, Andrzej, Sicinski, Rafal R., Schnoes, Heinrich K., Perlman, Kato L., Phelps, Mary E.
• Primary Examiner(s): Robinson, Douglas W.
• Assistant Examiner(s): Lipovsky, Joseph A.
• Application Number:
  US07/188,334
• Time in Patent Office: 438 Days
• Field of Search: 260/397.2, 514/167
• US Class Current: 552/653
• CPC Class Codes: C07C 401/00 Irradiation products of cholesterol or its derivatives; Vitamin D derivatives, 9,10-seco cyclopenta[a]phenanthrene or analogues obtained by chemical preparation without irradiation

Abstract

The invention relates to a method for preparing vitamin D-related compounds and to certain intermediate compounds in such process. The intermediate compounds are characterized by an aldehyde or ester in the C-22 position in the side chain. The presence of such groups permit facile side chain additions for the preparation of vitamin D derivatives.

Claims

1. Compounds having the formula:

##STR5## where X and Y, which may be the same or different, are each selected from the group consisting of hydrogen, and a hydroxy-protecting group, and where W is selected from the group consisting of CHO, COO-alkyl and COO-aryl.

2. The compounds of claim 1, wherein X and Y are hydrogen.

3. The compounds of claim 2 where W is CHO.

4. The compound of claim 2, where W is COOCH₃.

5. The compounds of claim 1, wherein X and Y are hydroxy-protecting groups

6. Compounds according to claim 5 where W is CHO .

7. Compounds according to claim 3 where W is COOCH₃.

8. The compound of claim 1, wherein X and Y are t-butyl-dimethylsilyl, and W is CHO.

9. A compound of the formula:

##STR6## wherein R is selected from the group consisting of alkyl, hydroxylated alkyl, hydroxy-protected-hydroxylated alkyl, fluoro-substituted alkyl, fluoro-substituted hydroxylated alkyl and fluoro-substituted hydroxy-protected alkyl, and where X and Y, which may be the same or different, are each selected from the group consisting of hydrogen and a hydroxy-protecting group.

10. A method for preparing vitamin D compounds of the formula ##STR7## wherein R is selected from the group consisting of alkyl, hydroxylated alkyl, hydroxy-protected hydroxylated alkyl, fluoro-substituted alkyl, fluoro-substituted hydroxylated alkyl and fluoro-substituted hydroxy-protected alkyl, and where X and Y, which may be the same or different, are each selected from the group consisting of hydrogen and a hydroxy-protecting group, which comprises, treating a C-22-aldehyde compound of the formula ##STR8## where X and Y are as defined above, with a phenylsulfone derivative of the formula

View Dependent Claims (11, 12, 13, 14, 15, 16, 17)

11. The method of claim 10 where X and Y are hydroxyprotecting groups.

12. The method of claim 10 or of claim 11 where R is an alkyl group.

13. The method of claim 10 or of claim 11 where R is an hydroxylated alkyl group or a hydroxy-protected hydroxylated alkyl group.

14. The method of claim 10 or of claim 11 where R is a fluoro-substituted alkyl group.

15. The method of claim 10 or of claim 11 where R is a fluoro-substituted hydroxylated alkyl group, or a fluoro-substituted hydroxy-protected alkyl group.

16. The method of claim 11 where R is hydroxy-protected 3-methyl-3-hydroxy-2-butyl.

17. The method of claim 11 where R is hydroxy-protected 2-methyl-2-hydroxypropyl.