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US 4,046,760 AGranted
Process for preparing 1-.alpha.-hydroxy cholesterol derivatives
AssigneeMerck & Co., Inc.
InventorsHoward Jones, Robert A. Frankshun
Life of this patent
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Abstract
Improved processes are described for introducing a 1-.alpha.-hydroxy group into the cholesterol ring system. Novel intermediates and their preparation are disclosed.
Claims6
A process for the preparation of a 1.alpha.-hydroxycholes-5-enol of the formula:
- ##STR3## wherein R.sub.24 is a member selected from the group consisting of hydrogen and methyl and R.sub.25 is a member selected from the group consisting of hydrogen and hydroxy and wherein the dashed line at C-22-23 represents the optional presence of a double bond, which comprises:
- p1 a. treating R.sub.24, R.sub.25 -.DELTA..sup.4 -cholestene-3-one of formula I with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone in the presence of a hydrocarbon solvent having a boiling point of about 70.degree. to about 120.degree. C. to produce R.sub.24, R.sub.25 -.DELTA..sup.1,4 -cholestediene-3-one of formula II;
- b. rearranging the product of Step (a) with a proton abstracting base to produce R.sub.24, R.sub.25 -.DELTA..sup.1,5 -cholestediene-3-one of formula III;
- c. treating the product of Step (b) with a reducing agent capable of reducing a keto group to a hydroxy group to produce R.sub.24, R.sub.25 -.DELTA..sup.1,5 -cholestediene-3.beta.-ol of formula IV;
- d. treating the product of Step (c) with an oxidizing agent capable of epoxidizing the 3-hydroxy-.DELTA.'-system to produce R.sub.24,R.sub.25,1.alpha.,2.alpha.-epoxy-.DELTA..sup.5 -cholestene-3.beta.-ol of formula V;
- and
- e. treating the product of Step (d) with a reducing agent capable of reducing the epoxide group to a hydroxy group to produce R.sub.24,R.sub.25,1.alpha.-hydroxycholest-5-enol of formula VI.
4 more elements
A process for the preparation of a 1.alpha.-hydroxycholest-5-enol of the formula:
- ##STR4## wherein R.sub.24 is a member selected from the group consisting of hydrogen and methyl and R.sub.25 is a member selected from the group consisting of hydrogen and hydroxy, and wherein the dashed line at C-22-23 represents the optional presence of a double bond, which comprises:
- a. acetylating R.sub.24,R.sub.25 -.DELTA..sup.1,5 -cholestediene-3.beta.-ol of formula IV with acetic anhydride to produce R.sub.24,R.sub.25 -.DELTA..sup.1,5 -cholestediene-3-.beta.-acetate of formula VII;
- b. treating the product of Step (a) with an oxidizing agent capable of epoxidizing the 3-hydroxy-.DELTA.'-system to produce R.sub.24,R.sub.25,1.alpha.,2.alpha.-epoxy-.DELTA..sup.5 -cholestene-3.beta.-acetate of formula VIII;
- and
- c. treating the product of Step (b) with a reducing agent capable of reducing the epoxide group to a hydroxy group to produce R.sub.24,R.sub.25,1.alpha.-hydroxycholest-5-enol of formula VI.
2 more elements
A 1.alpha.,2.alpha.-epoxy-.DELTA..sup.5 -cholestene-3.beta.-ol of the formula:
- ##STR5## wherein R.sub.24 is a member selected from the group consisting of hydrogen and methyl, R.sub.25 is a member selected from the group consisting of hydrogen and hydroxy and R is a member selected from the group consisting of hydrogen and acetyl and wherein the dashed line at C-22-23 represents the optional presence of a double bond.
Dependencies are inferred from the claim text.