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US 9,540,311 B2Granted
Processes and intermediates for the preparations of isomer free prostaglandins
AssigneeChirogate International Inc.
InventorsShih-Yi Wei, Yu-Chih Yeh, Min-Kuan Hsu, Li-Ta Kao
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Abstract
Novel processes for the preparation of a compound of Formula I-2 substantially free of the 5,6-trans isomer: wherein R2, R3 and R4 are as defined in the specification are provided. Novel intermediates for the preparations of isomer free Prostaglandins and derivatives thereof are also provided.
Claims2
A process for preparing a compound of Formula III substantially free of the 5,6-trans isomer:
- wherein
- or a protecting group for carbonyl group;
- P1 and P2 are independently protecting groups for hydroxyl groups;
- is a single or double bond;
- R2 is a single bond or a C1-4-alkylene or —CH2O—;
- and R3 is a C1-7-alkyl or an aryl or an aralkyl, each of which is unsubstituted or substituted by a C1-4-alkyl, a halogen or a trihalomethyl, comprising the steps of:
- (1) reacting a compound of Formula VI containing 0˜5% 5,6-trans isomer:
- wherein R6 is C1-7-alkyl and P1 is a protecting group for hydroxyl group, with a cuprate derived from the compound of Formula IX-1, Formula IX-2 or Formula IX-3
- wherein
- , R2 and R3 are as defined above;
- Y is halogen;
- and R7 is C1-7-alkyl,
- to form a compound of Formula V-2
- wherein
- , P1, R2, R3 and R6 are as defined above,
- (2) reducing the oxo group and hydrolyzing the COOR6 group in the compound of Formula V-2, to form a compound of Formula IV-1
- wherein
- , P1, R2 and R3 are as defined above, and
- (3) macrolactonizing a compound of Formula IV-1 to form a compound of Formula III.
16 more elements
A process for preparing a compound of Formula III substantially free of the 5,6-trans isomer:
- wherein
- or a protecting group for carbonyl group;
- P1 and P2 are independently protecting groups for the hydroxyl groups;
- is a single or double bond;
- R2 is a single bond or a C1-4-alkylene or —CH2O—;
- and R3 is a C1-7-alkyl or an aryl or an aralkyl, each of which is unsubstituted or substituted by a C1-4-alkyl, a halogen or a trihalomethyl,
- comprising the steps of:
- (1) semi-reducing the compound of Formula VIII,
- wherein
- , P1, R2, and R3 are as defined above,
- to form a compound of Formula VII
- wherein
- , P1, R2, and R3 are as defined above,
- (2) subjecting the compound of Formula VII to a Wittig reaction to form a compound of Formula IV-1
- wherein
- , P1, R2 and R3 are as defined above, and
- (3) macrolactonizing a compound of Formula IV-1 to form a compound of Formula III.
14 more elements
Dependencies are inferred from the claim text.