A bioinspired, one-step total synthesis of peshawaraquinone.

A concise synthesis of a stereochemically complex meroterpenoid, peshawaraquinone, the unsymmetrical dimerization of its achiral precursor, dehydro-α-lapachone, is reported. Enabled by reversible oxa-6π-electrocyclizations of 2-pyran intermediates, the base-catalyzed dimerization sets up an intramolecular (3 + 2) cycloaddition, with the formation of six stereocenters during the cascade. Combining the generation and dimerization of dehydro-α-lapachone allows a one-step total synthesis of peshawaraquinone from lawsone and prenal.

Biomimetic Synthesis Enables the Structure Revision of Littordials E and F and Drychampone B.

Structural reassignments for littordial E, littordial F, and drychampone B are proposed on the basis of consideration of their biosynthetic origin. The key step in the proposed biosynthesis of each of these meroterpenoids is an intermolecular hetero-Diels-Alder reaction between an -quinone methide and caryophyllene or humulene. Biomimetic total synthesis of the natural products gave sufficient material to allow their structure revision by NMR studies.