Platinum-Catalyzed α,β-Unsaturated Carbene Formation in the Formal Syntheses of Frondosin B and Liphagal

Abstract

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.

Total Syntheses of Liphagal: A Potent and Selective Phosphoinositide 3-Kinase α (PI3Kα) Inhibitor from the Marine Sponge Aka coralliphaga

“…18 Recently, the formal total synthesis of (±)-1 was reported by Ferreira et al (2017). 19 Related synthetic studies have also been reported by several other research groups. 20 The syntheses and biological evaluation of liphagal analogs were performed by Andersen et al 15,21 In this article, the total syntheses of 1 are reviewed with a particular focus on the synthetic strategies employed.…”

“…19 The retrosynthetic plan is outlined in Scheme 15. In this plan, the stage for construction of the tetracyclic ring system (i.e., 31 → 30) relies on Andersen's biomimetic approach 6 (see 6 → 5a + 5b in Scheme 7).…”

Deconstructive Reorganization: De Novo Synthesis of Hydroxylated Benzofuran

“…Lately, Winne and co‐workers have realized a convergent synthesis of 5‐ epi ‐Liphagal (8 steps) by using an acid‐catalyzed intermolecular [4+3] cycloaddition . Ferreira and co‐workers accomplished the formal synthesis of Liphagal (9 steps) by using a carbenoid mediated conjugate addition as the key strategy . Herein, we report a de novo synthetic route for the synthesis of Liphagal with the indium‐triggered arene cycloisomerization as key step.…”

The linker length of glucose–fipronil conjugates has a major effect on the rate of bioactivation by β‐glucosidase

“…Compounds 2a , 1b , 2c–2d , 3b , 8a , 8b , 8c , and 8d were prepared according to procedures found in the literature or with slight modifications. The reactions are shown in Schemes .…”