Synthesis and Pharmacological Properties of New Tetracyclic Forskolin Analogues

Abstract

New tetracyclic analogues of forskolin have been prepared by derivatization of the natural product. Treatment of a forskolin-derived cyclic thionocarbonate with 1,3-dimethyl-2-phenyl-1,3,2-diazaphospholidine resulted in the formation of a seven-membered cyclic carbonate derivative by an unprecedented rearrangement of an intermediate dialkoxycarbene or 1,3-dipole, whereas radical deoxygenation was followed by intramolecular cyclization with the double bond to form a third analogue. Two of the new analogues were investigated

Skeletal Transformations of Terpenoid Forskolin Employing an Oxidative Rearrangement Strategy

“…Previously, a series of forskolin analogues have been reported, − including the redox rearrangement products, acid-catalyzed rearrangement products, and base-catalyzed rearrangement products (Figure S12). , The base-catalyzed rearrangement product 3 bears a unique 6/7/5 tricyclic carbon skeleton, an oxygen bridging ring, making it an ideal precursor for next oxidative rearrangements (Scheme ).…”

Forskolin Editing via Radical Iodo- and Hydroalkylation

“…21 In an attempt to remove the 9-hydroxy group via the thiocarbonate 8 under classical radical conditions (Bu 3 SnH, AIBN), König and co-workers reported that, instead of the expected deoxygenated product, tetracyclic forskolin analogue 9 was obtained in a highly stereoselective manner, following regioselective cleavage of the thionocar-bonate moiety, 5-exo-trig cyclization of the resulting tertiary carbon-centered radical intermediate, and hydrogen atom transfer from the chain carrier reagent (Scheme 1). 19…”

“…18 Tetracyclic analogue 6 presenting a sevenmembered-ring carbonate moiety was prepared by König and co-workers by treatment of thionocarbonate 8 (see Scheme 1 for structure) with 1,3-dimethyl-2-phenyl-1,3,2diazaphospholidine (Corey-Winter conditions). 19…”