Metal-oxo induced syn-oxidative polycyclizations of hydroxypolyenes: Biomimetic synthesis of polycyclic ether natural products

Abstract

Abstract

Epoxide‐Opening Cascades in the Synthesis of Polycyclic Polyether Natural Products

“…[84,85] According to this hypothesis, monensin A may be produced from an all-Z triene precursor (an all-Z isomer of 26) through a series of oxidative cyclizations proceeding via a [2+2] mechanism that involves the action of an iron-containing monooxygenase ( Figure 4). Synthetic studies by Townsend himself [84] and work on model systems closely related to the proposed all-Z premonensin triene by McDonald [86,87] provided further support for this hypothesis. The issue of stereochemistry of the alkenes in the monensin A precursor was also raised by Leadlay et al Speculating that the cascade of epoxide opening may be initiated by activation of the methyl ketone electrophile, Leadlay proposed that a Z,Z,Ealkene would be required en route to monensin A.…”

Biomimetic Synthesis of Polyether Natural Products via Polyepoxide Opening

“…Townsend suggested that monensin A may be produced from an all-(Z) isomer of 25 through a series of oxidative cyclizations proceeding via a [2+2] mechanism involving an Fe-containing monooxygenase (Figure 15.3b). Related proposals were considered by McDonald [64,65] and Leadlay [66]. Upon sequencing the monensin biosynthetic gene cluster [66,67], Leadlay found that deletion of monCI from the producing organism caused accumulation of all-(E) premonensin triene 25.…”

Biomimetic Synthesis of Deca- and Dodecaketide-Derived Quinone Antibiotics

“…Three of the four linearly condensed rings of the anthracyclines are already assembled in the anthraquinone part. For successful transformation into ε-rhodomycinone (29) and related compounds, however, the problem of regioselective attachment of the appropriate side chains in vicinal positions had to be solved. Two solutions to this important problem of regioselectivity have been published, both making use of 1-hydroxy-4,5-dimethoxy-9,10-anthraquinone (24) as a key intermediate.…”

“…Reaction at higher temperatures results in elimination of a hydroxy group through an intramolecular redox process, [50] while at low temperatures the initially formed hydroxyalkyl products can be isolated. [52,53] Both versions are useful in anthracycline synthesis, as demonstrated in Scheme 7 for ε-rhodomycinone (29). [54] The leuko form of 24 was prepared by sodium dithionite reduction; treatment of the dihydroquinone with formaldehyde gave the hydroxymethylation product, which was chlorinated with thionyl chloride to provide 25.…”

“…These few examples may suffice to introduce the reader to the specific features of biomimetic synthesis; for other important classes of biomimetic natural product synthesis, see reviews on porphyrinoids, [25] alkaloids, [11,12,26,27] pericyclic key reactions, [28] and polycyclic ether natural products. [29] In the following sections, deca-and dodecaketide-derived biomimetic-type syntheses of quinone antibiotics developed in our laboratory are described.…”