This invention relates generally to the synthesis of .sup.12-Prostaglandin J product using stereoretentive ruthenium olefin metathesis catalysts supported by dithiolate ligands. .sup.12-Prostaglandin J products were generated with excellent selectivity (>99% Z) and in moderate to high/good yields (47% to 80% yield; 58% to 80% yield).

Novel processes for the preparation of a compound of Formula I-2 substantially free of the 5,6-trans isomer: ##STR00001##
wherein ##STR00002##
R.sub.2, R.sub.3 and R.sub.4 are as defined in the specification are provided. Novel intermediates for the preparations of isomer free Prostaglandins and derivatives thereof are also provided.

Novel processes for the preparation of a compound of Formula I-2 substantially free of the 5,6-trans isomer: ##STR00001##
wherein ##STR00002##
R.sub.2, R.sub.3 and R.sub.4 are as defined in the specification are provided. Novel intermediates for the preparations of isomer free Prostaglandins and derivatives thereof are also provided.

The present invention relates to a cost-effective and efficient method for preparing treprostinil with high purity, and an intermediate therefor.

The present invention provides a method for separating a compound represented by Formula (1) or (2) [in the formula, P.sup.1 is a hydrogen atom or a protective group of a hydroxyl group, R.sup.1 is a linear or branched C.sub.1-6 alkyl group that may be substituted with a phenyl group, A is an alkenylene group, and R.sup.2 is a hydroxyl group, a C.sub.1-3 alkoxy group, a mono(C.sub.1-3 alkyl)amino group, or a di(C.sub.1-3 alkyl)amino group] from a geometrical isomer thereof, in which the geometrical isomer is a geometrical isomer in a double bond included in A, the method including processing a mixture containing the compound and the geometrical isomer thereof by a chromatographic method using an acidic functional group-modified silica gel as a stationary phase.

##STR00001##

The present invention provides a method for separating a compound represented by Formula (1) or (2) [in the formula, P.sup.1 is a hydrogen atom or a protective group of a hydroxyl group, R.sup.1 is a linear or branched C.sub.1-6 alkyl group that may be substituted with a phenyl group, A is an alkenylene group, and R.sup.2 is a hydroxyl group, a C.sub.1-3 alkoxy group, a mono(C.sub.1-3 alkyl)amino group, or a di(C.sub.1-3 alkyl)amino group] from a geometrical isomer thereof, in which the geometrical isomer is a geometrical isomer in a double bond included in A, the method including processing a mixture containing the compound and the geometrical isomer thereof by a chromatographic method using an acidic functional group-modified silica gel as a stationary phase.

##STR00001##

Embodiments include a system including a sealed prefilled drug-reservoir. The drug-reservoir may include a unit dosage of treprostinil in a sterile fluid composition. The composition may not include an antimicrobial preservative. The treprostinil may be present at a dosage of between 0.1 mg/mL and 25 mg/mL. In addition, the treprostinil may be treprostinil sodium Furthermore, the composition may include sodium chloride. The composition may also include a sodium ion from sodium chloride in a concentration from 3000 to 4500 ppm. The composition may not include metacresol.

The present invention relates to a novel production method of a novel prostaglandin derivative or a pharmaceutically acceptable salt thereof useful as a medicament, and an intermediate therefor. According to the present invention, a production method of a novel prostaglandin derivative or a pharmaceutically acceptable salt thereof including a conversion step from a compound represented by the following formula 3 to a compound represented by the formula 1 can be provided:

##STR00001##

wherein each symbol is as defined in the DESCRIPTION.

The present invention relates to a process for preparing latanoprostene bunod and an intermediate therefor. In accordance with the preparation process of the present invention, latanoprostene bunod can be efficiently and cost-effectively prepared while reducing side reactions.

The present invention relates to a process for preparing latanoprostene bunod and an intermediate therefor. In accordance with the preparation process of the present invention, latanoprostene bunod can be efficiently and cost-effectively prepared while reducing side reactions.