Chemical Transformations of 9,11-Ethano-13,15-isoxazolinoprostanoids

Chemical transformations of 9,11-ethano-13,15-isoxazolinoprostanoids furnished new prostanoids with a bufunctional fragment of -hydroxyketone and -aminoalcohol in the -chain. The reaction of -hydroxyketones with methanesulfonyl chloride gave rise to prostanoids with an enone component in the -chain. 9,11-Ethano-16-thiaprostanoids were prepared for the first time by nucleophilic addition of thiols to the polarized double bond in the -chain. The 1,3-dipolar addition to terminal alkenes of nitrile oxides generated from nitromethylene derivatives of bicycloheptane provided 9,11-ethano-13,15-isoxazolinoprostanoids with an alkyl, phenyl, or additional heterocyclic fragment in the -chain.     

Synthesis of 9,11-Ethano-13,15-isoxazolinoprostanoids,PGH Analogs

The 1,3-dipolar addition to terminal alkenes of nitrile oxides generated from nitromethylene derivatives of bicycloheptane provided 9,11-ethano-13,15-isoxazolinoprostanoids with alkyl, phenyl, or additional heterocyclic fragment in the -chain.     

New 9,11-Ethano-7-oxo-13-thia Prostanoids

New 9,11-ethano analogs of prostaglandin endoperoxides containing a sulfur atom in position 13 were synthesized by nucleophilic addition of thiols at the polarized double bond of 2-acylbicyclo[2.2.1]hept-2-enes. Physicochemical properties and biological activity of the products were studied.     

Synthesis and Dehydration of endo-2-(3-R-Isoxazol-5-yl)-1,7,7-trimethylbicyclo[2.2.1]heptan-exo-2-ols

endo-2-Ethynyl-1,7,7-trimethylbicyclo[2.2.1]heptan-exo-2-ol reacts with nitrile oxides, yielding endo-2-(3-R-isoxazol-5-yl)-1,7,7-trimethylbicyclo[2.2.1]heptan-exo-2-ols. Treatment of the latter with methanesulfonyl chloride in pyridine leads to dehydration and formation of mixtures of the corresponding 1-(3-R-isoxazol-5-yl)-3,3-dimethyl-2-methylenebicyclo[2.2.1]heptanes and 2-(3-R-isoxazol-5-yl)-1,7,7-trimethylbicyclo[2.2.1]hept-2-enes at a ratio of 2:1.