Processes and intermediates for the preparations of isomer free prostaglandins

摘要

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.

主权项

1. A process for preparing a compound of Formula I-2 substantially free of the 5,6-trans isomer: wherein  is   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; R4 is C1-7-alkyl, comprising the steps of: (1) macrolactonization of a compound of Formula IV-1 containing 0˜5% 5,6-trans isomer wherein  is  or a protecting group for the carbonyl group; P1 and P2 are protecting groups for hydroxyl groups; , R2 and R3 are as defined above, to form a compound of Formula III: wherein  , P1, R2 and R3 are as defined above for Formula IV-1; (2) removing P1 or/and P2; and (3) opening the macrolactone ring by transesterification.