Benzodioxane prostacyclin analogs

#(1) Field of the Invention

#The compounds of the present invention are related to novel benzodioxane prostacyclin analogues and intermediates thereof. In more detail, this invention relates to the compounds represented by the general formula (I) or the salts thereof, which have prostacyclin (prostaglandin I.sub.2 ; prostaglandin is abbreviated to PG hereinafter) like antiulcer activity and platelet aggregation inhibitory activity, and the intermediate thereof.

#General formula: ##STR2## (wherein R.sub.1 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, or phenoxyalkyl; R.sub.2 is hydrogen, lower alkyl or aralkyl; R.sub.3 is hydrogen or a protecting group; A is ethylene or vinylene; the wavy line indicates .alpha. or .beta. configuration or their mixture)

#In a nitrogen atmosphere, 1.83 ml (2.01 mmol) of n-pentyl-magnesium bromide (1.1N, in THF) is added dropwise to 962 mg (1.68 mmol) of the aldehyde II (prepared in (20)) in 20 ml of dry THF at -78.degree. C. After stirring for 15 minutes at the same temperature, the reaction is quenched by the addition of a saturated aqueous solution of ammonium chloride. The reaction mixture is extracted with ethyl acetate three times and the extract is washed with water and a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. The residue is purified by the column chromatography on silica gel (Merck, Lobar column, size B, two columns, ethyl acetate:toluene=1:10 to 1:6) to give 517 mg of the less polar isomer Iaa-a as an oil and 252 mg of the more polar isomer Ica-a as crystals in 47.7% and 20.7% yield, respectively.

#Compound Iaa-a

#.sup.1 H-NMR: .delta. (CDCl.sub.3) 0.87 (3 H, t, J=6 Hz), 1.03 (9 H, s), 1.00.about.1.90 (9 H, m), 2.05.about.2.25 (2 H, m), 2.76.about.3.03 (1 H, m), 3.79 (3 H, s), 3.80.about.4.30 (4 H, m), 4.72 (2 H, s), 5.22.about.5.70 (2 H, m), 6.40.about.6.87 (3 H, m), 7.30.about.7.50 (6 H, m), 7.60.about.7.80 (4 H, m) ppm.