frondosin-b and liphagal

Liphagal and frondosin B are two marine-derived secondary metabolites sharing a very similar polyfused-benzofuran skeleton. The two tetracyclic meroterpenoids were isolated from marine sponges, both featuring a 6-5-7-6 fused ring system. A preliminary bioactive study shows that (+)-liphagal is a selective kinase (PI3K α) inhibitor, while (+)-frondosin B is shown to inhibit the binding of the cytokine interleukin-8 (IL-8) to its receptor, CX-CLR1/2. The unique structures and interesting biological profiles of these two meroterpenoids have attracted considerable attention from synthetic chemists. Herein we summarize the synthetic efforts with respect to (+)-liphagal and (+)-frondosin B during the past two decades.

Topics: Animals; Benzofurans; Chemistry, Pharmaceutical; Heterocyclic Compounds, 4 or More Rings; Molecular Structure; Phosphoinositide-3 Kinase Inhibitors; Porifera; Receptors, Interleukin-8; Stereoisomerism; Terpenes

Formal syntheses of tetracyclic terpenoids frondosin B and liphagal are described. Both synthetic routes rely on the use of platinum-catalyzed α,β-unsaturated carbene formation for the key C-C bond forming transformations. The successful route toward frondosin B utilizes a formal (4 + 3) cycloaddition, while the liphagal synthesis features the vinylogous addition of an enol nucleophile as a key step. Both synthetic routes are discussed, revealing insights into structural requirements in the catalytic α,β-unsaturated carbene reaction manifold.

Topics: Catalysis; Cycloaddition Reaction; Heterocyclic Compounds, 4 or More Rings; Methane; Molecular Structure; Oxidation-Reduction; Phenols; Platinum; Stereoisomerism; Terpenes

A recently developed (4+3) cycloaddition between dienes and furfuryl alcohols, as precursors of oxyallyl-type cations, has been used as a key step in the racemic syntheses of two natural products: frondosin B and liphagal. This work demonstrates the synthetic potential of this cycloaddition reaction, and offers a short synthetic route to an interesting family of natural products. A full account of these synthetic studies is presented, further illustrating the mechanism, scope, and limitations of this straightforward synthetic method for seven-membered rings.

Topics: Biological Products; Crystallography, X-Ray; Cycloaddition Reaction; Cycloheptanes; Heterocyclic Compounds, 4 or More Rings; Molecular Conformation; Stereoisomerism; Terpenes