Synthesis of the key component for preparation of 6-ketoprostaglandins by a two-component coupling process: synthesis of 6-keto-prostaglandin E1, ornoprostil and Δ2-trans-6-ketoprostaglandin E1

Abstract

Starting with commercially available (3S, 4R)-3-(methoxymethyloxy)-2-methylidene-4-siloxycyclopentanone 2, useful 6-keto-prostaglandin intermediates 1 have been prepared in good yields by a sequence of reactions which includes treatment with NaBr in the presence of BF₃·OEt₂, Pd-catalysed coupling of the resulting 2-bromomethyl-4-siloxycyclopent-2-enone 3 with the alkenylborane 4 or 9 and conversion of the alkenyl moiety into an epoxy and then into a keto group. The synthesis of 6-keto-PGE₁, ornoprostil and Δ²-trans-6-keto-PGE₁ by using 1 is also described.