Method of synthesizing 1alpha-hydroxy-2-methylene-19-nor-homopregnacalciferol

• US 7,208,484 B2
• Filed: 05/17/2004
• Issued: 04/24/2007
• Est. Priority Date: 03/29/2002
• Status: Active Grant

• Current Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Original Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Inventors: DeLuca, Hector F., Gowlugari, Sumithra, Sicinski, Rafal R.
• Primary Examiner(s): QAZI, SABIHA NAIM
• Application Number:
  US10/847,040
• Publication Number:
  US 20040220418A1
• Time in Patent Office: 1,072 Days
• Field of Search: 514/167, 552/653
• US Class Current: 514/167
• 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
• CPC Class Codes: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

A method of making 1α-hydroxy-2-methylene-19-nor-homopregnacalciferol. The method includes the steps of condensing a bicyclic ketone with an allylic phosphine oxide to produce a protected 19-nor-pregnacalciferol analog, thereafter cleaving the protecting group to form 22-alcohol, converting the alcohol to an ester, reducing the ester to 17β-isopropyl-19-nor-vitamin D analog, and finally deprotecting the 17β-isopropyl derivative to form the desired compound.

Claims

1. A compound having the structure:

2. The compound of claim 1 wherein Y₁ and Y₂ are both a t-butyl-dimethylsilyl group.

3. A compound having the structure:

4. The compound of claim 3 wherein Y₁ and Y₂ are both a t-butyl-dimethylsilyl group.

5. A compound having the structure:

6. The compound of claim 5 wherein R₁ is a tosyl group or a mesyl group.

7. The compound of claim 5 wherein R₁ is a triethylsilyl group.

8. The compound of claim 5 wherein Y₁ and Y₂ are both a t-buyl-dimethylsilyl group.

9. The compound of claim 8 wherein R₁ is a tosyl group.

10. The compound of claim 8 wherein R₁ is a triethylsilyl group.

11. A compound having the structure:

12. The compound of claim 11 wherein Y₁ and Y₂ are both a t-butyl-dimethylsilyl group.