A Novel Chemo‐selective Epoxidation across Acrylate Ester: Synthesis of New Water‐Soluble Forskolin Analogues

Abstract

While removing the TBDMS group from OH protection, a novel epoxidation reaction occurred across acrylate ester attached to a forskolin fragment. Besides spectroscopic data, the epoxide formation was confirmed by ring opening with a secondary amine. This unique epoxidation reaction, to our knowledge, is not known in the literature. This reaction led us to discover a simple deblocking protocol. The epoxide and the desired Michael substrates were used to introduce imidazole into forskolin.

Aza-Michael Addition of Imidazole Analogues

“…The imidazole ring was also incorporated into forskolin derivatives in order to enhance its positive inotropic activity. 114 Compounds 73 were treated with imidazole (2-4 equiv) under gentle reaction conditions (CH 2 Cl 2 , r.t., 12-16 h) to provide the final products in 77% (74a) and 92% (74b) yields (Scheme 20).…”