Separation of mixed diastereoisomers of zearalanol

Claim 2

The process of claim 2 wherein the ratio of acetic acid to zearalanol in the solution prepared in step (i) is about 2 to 10 milliliters per gram of zearalanol.

Claim 3

The process of claim 1 wherein, in step (ii), the solution is maintained at about 15* to120* C., for at least about 18 hours.

Claim 4

The process of claim 1 wherein, in step (iii), the mixed esters are in solution in methanol for their separation by fractional crystallization, and the fractional crystallization is effected by cooling the methanolic solution down to a temperature of about 30* C. or lower to selectively crystallize out of solution the 6''-acetate of the high melting diastereoisomer of zearalanol.

Claim 5

The process of claim 5 wherein the methanolic solution contains about 10 to 20 milliliters of methanol per gram of zearalanol, 6''-acetate prior to the crystallization of the 6''-acetate of the high melting zearalanol diastereoisomer therefrom.

Claim 6

The process of claim 6 wherein the methanolic solution is substantially continuously agitated during the crystallization therefrom of the 6''-acetate of the high melting diastereoisomer of zearalanol.

Claim 7

The process of claim 1 wherein the de-esterification of the acetate groups of the separated 6''-acetate esters of the diastereoisomers of zearalanol is effected by subjecting the esters to transesterification with a monohydric alkanol of one to five carbon atoms.

Claim 8

The process of claim 8 wherein the transesterification is acid catalyzed.

Claim 9

The process of claim 9 wherein the displacing alcohol is methanol.

Claim 10

The process of claim 10 wherein the acid catalyst employed is sulfuric acid or hydrochloric acid.

Claim 11

The process of claim 11 wherein the transesterification is effected at about 50* to 65* C.

Claim 12

The process of claiM 12 wherein the ratio of methanol to zearalanol, 6''-acetate employed in the transesterification reaction is about 2.5 to 10 milliliters per gram of zearalanol, 6''-acetate.

Claim 13

The process of claim 13 wherein the molar ratio of acid catalyst to zearalanol, 6''-acetate employed in the transesterification reaction is about 0.001 to 0.1.

Claim 14

A process of separating mixed diastereoisomers of zearalanol which comprises i. dissolving the mixed diastereoisomers in glacial acetic acid at a ratio of about 3 to 7 milliliters of glacial acetic acid per gram of zearalanol; ii. maintaining the resultant solution at about 15* to 120* C. for about 18 to 36 hours so as to effect esterification of the aliphatic hydroxyl group of the zearalanol, thus yielding mixed 6''-acetate esters of the diastereoisomers of zearalanol; iii. forming a methanolic solution of the mixed 6''-acetate esters of the diastereoisomers of zearalanol, said solution containing about 12 to 15 milliliters of methanol per gram of zearalanol, 6''-acetate, and cooling the solution, while substantially continuously agitating same, down to a temperature of about 5* to 20* C., so as to selectively crystallize the 6''-acetate of the high melting diastereoisomer of zearalanol out of the solution, thereby separating the 6''-acetate esters of the diastereoisomers of zearalanol; and iv. transesterifying the acetate groups of the 6''-acetate esters of the diastereoisomers of zearalanol with methanol so as to yield separated diastereoisomers of zearalanol, said transesterification reaction being effected with acid catalysis at about 50* to 65* C., using about 2.5 to 10 milliliters of methanol per gram of zearalanol, 6''-acetate and about 0.01 to 0.1 moles of sulfuric or hydrochloric acid, as catalyst, per mole of zearalanol, 6''-acetate.

Claim 15

The process of claim 15 wherein step (ii) is conducted in the absence of acidic catalyst and at a temperature of about 75* to 120* C.

Claim 16

The process of claim 15 wherein step (ii) is conducted in the presence of about 0.1 to 5 parts of concentrated sulfuric acid per each 100 parts by weight of CH3COOH and at a temperature of about 15* to 40* C.