ortho‐Quinols in (Bio)Synthesis of Natural Products

Abstract

6-Alkyl-6-hydroxycyclohexa-2,4-dienone derivatives, commonly referred to as ortho-quinols, and their simple ester and ether variants constitute a class of organic compounds that aroused much interest amongst chemists over the past 70 years for several reasons related to organic synthesis, natural product chemistry and biochemistry. It was very early on that organic chemists understood the potential of the unique yet versatile chemical reactivity of such compounds to synthesize more complex structures, and it soon emerged that ortho-quinols could constitute key intermediates in the biosynthesis of certain natural products of various origins. This minireview discusses the chemistry of ortho-quinols from the point of view of their role in the synthesis and biosynthesis of natural products. Examples of completed syntheses of natural products mostly taken in the literature of the last 20 years or so, together with some chosen pieces from older but pioneering and most remarkable works, are highlighted to illustrate this discussion.

Breeding Novel Chemistry in Willow: New Hetero Diels–Alder Cyclodimers from Arbusculoidin and Salicortin Suggest Parallel Biosynthetic Pathways

“…The observed dimeric products are believed to have arisen from an inter-molecular Diels-Alder reaction of glycosylated orthoquinols such as (6). Such reactions are well documented to be exquisitely regio-and stereospecific to yield totally endo-selective products in both natural and synthetic scenarios [14,15]. In nature, the [4+2] dimerization reaction of the orthoquinols is believed to be spontaneous, rather than enzyme-catalysed.…”

Total Synthesis of the Bacterial ortho-Quinol (+)-Strepantibin A through Iodyl-Type λ5-Iodane-Promoted Asymmetric Hydroxylative Phenol Dearomatization

“…1,2 Naturally occurring ortho-quinols are usually reactive intermediates in the biosynthesis of natural products of plant or microbial origin and their benzoid variants are notably often prone to undergoing cyclodimerization events. 2 Strepantibin A (1) is thus another example among a few known nondimerizing natural ortho-quinols in the benzoid series, such as the humulones and wasabidienones. 2,3 At first glance, 1 does not appear as a particularly complex target for chemical synthesis, but the archetypal ortho-quinol structure of such a promising antitumoral compound led us to consider it as a novel target for challenging the use of chiral iodyl-type λ 5 -iodane reagents in stereoselective hydroxylative phenol dearomatization (HPD) reactions.…”

“…2 Strepantibin A (1) is thus another example among a few known nondimerizing natural ortho-quinols in the benzoid series, such as the humulones and wasabidienones. 2,3 At first glance, 1 does not appear as a particularly complex target for chemical synthesis, but the archetypal ortho-quinol structure of such a promising antitumoral compound led us to consider it as a novel target for challenging the use of chiral iodyl-type λ 5 -iodane reagents in stereoselective hydroxylative phenol dearomatization (HPD) reactions. Such a tactic enabled us to achieve the chemical synthesis of several natural products and analogues thereof, 3b,4 and is here investigated for generating 1 from phenolic para-terphenyl precursors (Scheme 1).…”

“…The structure of strepantibin A ( 1 ) is based on a para -terphenyl core on which only the middle ring is functionalized and dearomatized, harboring a single stereogenic carbon center at a tertiary alcohol function (Scheme ). This functionalized ring constitutes a motif that is trivially called ortho -quinol (i.e., 6-alkyl-6-hydroxycyclohexa-2,4-dienone) and that could be (bio)­synthetically generated through oxidation of a phenolic or catecholic precursor. , Naturally occurring ortho -quinols are usually reactive intermediates in the biosynthesis of natural products of plant or microbial origin and their benzoid variants are notably often prone to undergoing cyclodimerization events . Strepantibin A ( 1 ) is thus another example among a few known nondimerizing natural ortho -quinols in the benzoid series, such as the humulones and wasabidienones. , …”