Studies toward the Total Synthesis of Parvifolals A/B: An Intramolecular o-Quinone Methide [4 + 2]-Cycloaddition To Construct the Central Tetracyclic Core

Abstract

Two different approaches funded upon the intramolecular [4 + 2]-cycloaddition of in situ generated o -quinone methides have been explored to construct the central tetracyclic core of parvifolals A/B. At the outset, a cross-pinacol coupling of 2-formyl tri- O -methyl resveratrol with 4-methoxysalicylaldehyde followed by acid treatment was found to provide the desired tetracyclic core with an internal olefin. The requisite pendant aryl group has been introduced by a Pd-catalyzed direct coupling of corresponding diazonium salt.

Chiral phosphoric acid catalyzed enantioselective inverse-electron-demand oxa-Diels–Alder reactions to synthesize chiral tricyclic tetrahydropyran derivatives

“…14,15 Furthermore, the bicyclic trans-fused octahydropyranopyrrole and tetrahydro-pyranocyclopentane motifs as shown in Fig. 1b are privileged structures present in numerous natural products and bioactive molecules; [16][17][18][19] nevertheless, their analogues trans-fused octahydropyranofuran and octahydropyranopyran are hardly found in natural resources, and thus less explored in terms of synthesis and biological properties. Therefore, development of synthetic approaches to access those unprecedented skeletons will be highly desirable in terms of expanding the chemical space and structural diversity of trans-fused bicyclic ring systems and exploring their bioactivity.…”

Enantioselective access to tricyclic tetrahydropyran derivatives by a remote hydrogen bonding mediated intramolecular IEDHDA reaction

“…For example, natural products Englerin A ( 1 ) and Parvifolal A ( 2 ) (Fig. 1a ), which, respectively, exhibit selective cytotoxic activity for renal cancer cell lines and inhibitory activity against sbLOX-1, feature a central trans-fused tetrahydropyranocyclopentane motif A 1 , 2 . The analogous nitrogen atom-containing bicyclic structure—i.e.…”