Many natural products of plant or microbial origins are derived from enzymatic dearomative oxygenation of 2-alkylphenolic precursors into 6-alkyl-6-hydroxycyclohexa-2,4-dienones. These so-called ortho-quinols cyclodimerize via a remarkably selective bispericyclic Diels-Alder reaction. Whether or not the intervention of catalytic or dirigent proteins is involved during this final step of the biosynthesis of these natural products, this cyclodimerization of ortho-quinols can be chemically reproduced in the laboratory with the same strict level of site-specific regioselectivity and stereoselectivity. This unique yet unified process, which finds its rationale in the inherent chemical reactivity of those ortho-quinols, is illustrated herein by an efficient and bioinspired first chemical synthesis of one of the most structurally complex and synthetically challenging examples of such natural cyclodimers, the bisditerpenoid (+)-maytenone.
Keywords: asymmetric synthesis; cycloaddition; hypervalent compounds; total synthesis; transition states.
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