Method for the purification of prostaglandins
AssigneeJohnson Matthey Public Limited Company
InventorsRobert R. Hogan, Ronald Rossi
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Abstract
The present invention provides a method for the purification of a prostaglandin by supercritical fluid chromatography, said method comprising the use of a stationary phase and a mobile phase comprising carbon dioxide, provided that when the stationary phase is unmodified silica gel, the prostaglandin is not luprostiol. The invention also provides prostaglandins obtainable by the method.
Claims18
A method for the purification of a prostaglandin by supercritical fluid chromatography, said method comprising using a stationary phase and a mobile phase comprising carbon dioxide, wherein the stationary phase is a non-chiral stationary phase selected from the group consisting of 4 ethyl pyridine, 2-ethyl pyridine and pyridine urea or a chiral stationary phase and the prostaglandin is a compound of formula (I), a compound of formula (II), or a compound of formula (IV):
- wherein,
- V is C;
- W is
- X is CONR12R13 or CO2R12;
- Y is
- Z is C1-20-alkyl, C2-20-alkynyl, —O—(C6-20-aryl) or —(C1-20-alkyl)-(C5-20-aryl), wherein the aryl group is optionally substituted with one to three substituents selected from the group consisting of C1-20-alkyl, halo and C(halo)3;
- R1 and R2 are independently H or OH, or R1 and R2 together form
- R3 and R4 are independently H or OH;
- R5 and R6 are independently H or OH, or R5 and R6 together form
- R7 and R8 are independently H, OH, halo or C1-20-alkyl;
- R9 and R10 are independently H or C1-20-alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from CONR12R13, CO2R12, and CO2−-M+;
- R11 is C1-20-alkyl or —O—(C1-20-alkyl), wherein the alkyl group is optionally substituted with one or more substituents selected from CONR12R13, CO2R12, and CO2−-M+;
- R12 and R13 are independently selected from the group consisting of H and C1-20 alkyl;
- M+ is a counter cation;
- and
- Halo is fluorine, chlorine, bromine or iodine.
A method for the purification of latanoprost by supercritical fluid chromatography, said method comprising the use of a chiral stationary phase and a mobile phase comprising carbon dioxide.
A method for purifying a crude prostaglandin, comprising injecting the crude prostaglandin onto a column comprising a stationary phase, eluting the crude prostaglandin through the column using a mobile phase comprising supercritical carbon dioxide, and collecting a fraction comprising a purified prostaglandin, wherein the stationary phase is a non-chiral stationary phase selected from the group consisting of 4-ethyl pyridine, 2-ethyl pyridine and pyridine urea or a chiral stationary phase and the prostaglandin is a compound of formula (I), a compound of formula (II), or a compound of formula (IV):
- wherein,
- V is C;
- W is
- X is CONR12R13 or CO2R12;
- Y is
- Z is C1-20-alkyl, C2-20-alkynyl, —O—(C6-20-aryl) or —(C1-20-alkyl)-(C6-20-aryl), wherein the aryl group is optionally substituted with one to three substituents selected from the group consisting of C1-20-alkyl, halo and C(halo)3;
- R1 and R2 are independently H or OH, or R1 and R2 together form
- R3 and R4 are independently H or OH;
- R5 and R6 are independently H or OH, or R5 and R6 together form
- R7 and R8 are independently H, OH, halo or C1-20-alkyl;
- R9 and R10 are independently H or C1-20-alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from CONR12R13, CO2R12, and CO2−M+;
- R11 is C1-20-alkyl or —O—(C1-20-alkyl), wherein the alkyl group is optionally substituted with one or more substituents selected from CONR12R13, CO2R12, and CO2−-M+;
- R12 and R13 are independently selected from the group consisting of H and C1-20 alkyl;
- M+ is a counter cation;
- and
- Halo is fluorine, chlorine, bromine or iodine.
Dependencies are inferred from the claim text.