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Bispericyclic Diels–Alder Dimerization of ortho ‐Quinols in Natural Product (Bio)Synthesis: Bioinspired Chemical 6‐Step Synthesis of (+)‐Maytenone
Author(s) -
Peixoto Philippe A.,
El Assal Mourad,
Chataigner Isabelle,
Castet Frédéric,
Cornu Anaëlle,
Coffinier Romain,
Bosset Cyril,
Deffieux Denis,
Pouységu Laurent,
Quideau Stéphane
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202103410
Subject(s) - natural product , regioselectivity , stereoselectivity , chemistry , chemical synthesis , reactivity (psychology) , combinatorial chemistry , catalysis , biocatalysis , organic chemistry , stereochemistry , biochemistry , reaction mechanism , in vitro , medicine , alternative medicine , pathology
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.