Synthesis of steroids

• US 4,226,770 A
• Filed: 02/23/1979
• Issued: 10/07/1980
• Est. Priority Date: 02/10/1978
• Status: Expired due to Term

• Current Assignee: Emil T. Kaiser
• Original Assignee: Emil T. Kaiser
• Inventors: Kaiser, Emil T.
• Primary Examiner(s): Roberts, Elbert L.
• Application Number:
  US06/014,695
• Time in Patent Office: 592 Days
• Field of Search: 260/239.55 C
• US Class Current: 540/10
• CPC Class Codes: C07J 21/006 at position 3
• CPC Class Codes: C07J 31/006 not covered by C07J31/003
• CPC Class Codes: C07J 41/0094 containing nitrile radicals, including thiocyanide radicals
• CPC Class Codes: C07J 9/00 Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
• CPC Class Codes: C07J 9/005 containing a carboxylic function directly attached or attached by a chain containing only carbon atoms to the cyclopenta[a]hydrophenanthrene skeleton

Abstract

The synthesis of 1α,25-dihydroxycholesterol, 1α,25-dihydroxy-7-dehydrocholesterol and 1α,25-dihydroxycholecalciferol and other sterol derivatives from bile acids. Also the synthesis of 3,6-diketo steroids useful in the production of 1α,25-dihydroxycholesterol and other sterols which are biologically active or can be converted to biologically active sterols. The invention involves the sterols so produced and the processes by which they are prepared.

Claims

1. In a process for preparing a 3,6-diketo steroid compounds, the step of heating a compound having the structure:

##STR11## with a metal cyanide, where Q is an aryl or alkyl sulfonyl group to produce the compound having the structure;

##STR12##

2. A process as set forth in claim 1 in which said sulfonyl group is p-toluenesulfonyl.

3. A process as set forth in claim 1 in which said metal cyanide is potassium cyanide.

4. A process as set forth in claim 1 in which said said metal cyanide is sodium, lithium, or silver cyanide.

5. A process as set forth in claim 1 including the set of mixing a compound having the structure:

##STR13## with an aryl or alkyl sulfonyl halide to replace OH with a sulfonyl ester group to prepare said compound having the structure;

##STR14## where Q is an alkyl or aryl sulfonyl group.

6. A process as set forth in claim 5 in which said aryl sulfonyl halide is p-toluenesulfonyl halide.

7. A process as set forth in claim 5 including the step of mixing a compound having the structure:

##STR15## where R is a lower alkyl group, with an alkaline reducing agent to reduce the 24-carboxylic ester function to a 24-hydroxy group.

8. A process as set forth in claim 7 in which said reducing agent is a complex of aluminum hydride with sodium, potassium or lithium.

9. A process as set forth in claim 7 including the step of heating a compound having the structure:

##STR16## where R is a lower alkyl group with ethylene glycol and a sulfonic acid catalyst to prepare said compound having the structure;

##STR17##

10. A process as set forth in claim 9 in which said sulfonic acid is p-toluenesulfonic acid.

11. A process as set forth in claim 1 including the step of refluxing in an aqueous alcohol solution of said compound having the structure:

##STR18## with sodium or potassium hydroxide and acidifying the resulting compound to prepare a compound having the structure;

##STR19##

12. A process as set forth in claim 11 including the step of mixing in the presence of sodium or potassium hydroxide a solution of said compound having the structure:

##STR20## with an alkyl halide to prepare a compound having the structure;

##STR21## where R is alkyl.

13. A process as set forth in claim 12 where said alkyl halide is methyl iodide.

14. A process as set forth in claim 12 including the step of mixing a solution of a methyl magnesium halide, dissolved in an ether, with said compound having the structure:

##STR22## where R is alkyl to prepare a compound having the structure;

##STR23##

15. A process as set forth in claim 14 where said metallo-methyl complex is methyl magnesium bromide.

16. A process as set forth in claim 14 in which said ether solvent is tetrahydrofuran.

17. A process as set forth in claim 14 including the step of heating an aqueous acid-containing alcohol solution of said compound having the structure:

##STR24## to prepare a compound having the structure;

##STR25##

18. A process as set forth in claim 17 where the aqueous acid is sulfuric acid diluted with water.