Bispericyclic Diels–Alder Dimerization of ortho‐Quinols in Natural Product (Bio)Synthesis: Bioinspired Chemical 6‐Step Synthesis of (+)‐Maytenone

Abstract

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.

Hyperbaric reactions in organic synthesis. Progress from 2006 to 2021

“…The bisditerpenoid (+)-maytenone was prepared in an enzymatic-like two-step sequence from (+)-ferruginol (Scheme 26). 73 With the help of the Salen-type derived bisiodyl reagent ( 85 ), (+)-ferruginol was stereospecifically oxidised to dienone 84 . The latter was immediately subjected to 14 kbar pressure at r.t, and its subsequent cyclodimerization afforded the dimeric adduct as a single enantiomer in a 60% yield.…”

Biogenetic and biomimetic synthesis of natural bisditerpenoids: hypothesis and practices

“…166 In a recent study, Quideau and co-workers asymmetric synthesized 22 in high yield from the commercially available monomer (+)-dehydroabietylamine (22a) in a six-step reaction (Scheme 25). 167 The [4 + 2] cyclodimerization of ortho-quinols reactions catalyzed by chiral reagents is the key step in the process. Moreover, the…”

“…166 In a recent study, Quideau and co-workers asymmetric synthesized 22 in high yield from the commercially available monomer (+)-dehydroabietylamine ( 22a ) in a six-step reaction (Scheme 25). 167 The [4 + 2] cyclodimerization of ortho -quinols reactions catalyzed by chiral reagents is the key step in the process. Moreover, the diastereoisomer of 22 , dimer 279 , was also synthesized in the same study, and was proved to be the bisditerpenoid identified from Harpagophytum procumbens .…”

Bispericyclic Diels–Alder Dimerization of ortho‐Quinols in Natural Product (Bio)Synthesis: Bioinspired Chemical 6‐Step Synthesis of (+)‐Maytenone

“…This work has benefited from the analytical facilities of the CESAMO platform at the University of Bordeaux. We thank B. Kauffman and S. Massip (CNRS-UMS 3033) for conducting X-ray diffraction experiments and solving the structures of compounds 4 and 20, [34] Prof.C .K.J ankowski for kindly providing us with the NMR spectra of natural 4,and Dr A. Fedotova for her kind help in the use of the high-pressure equipment. Akzeptierte Fassung online: 14.…”