An RCM‐Based Total Synthesis of the Antibiotic Disciformycin B

Waser, Philipp; Altmann, Karl‐Heinz

doi:10.1002/anie.202004589

Cited by 14 publications

(15 citation statements)

References 34 publications

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“…The synthesis of iodide 12 began with conversion of methyl angelate ( 30 ) into angelic aldehyde, which was found to be configurationally labile (Scheme 1B) [11] . Therefore, angelic aldehyde was immediately used in a Still–Gennari olefination with 31 to give dienoate 32 , which was then reduced to give allylic alcohol 20 [12, 13] .…”

Section: Figurementioning

confidence: 99%

“…The synthesis of iodide 12 began with conversion of methyl angelate (30) into angelic aldehyde, which was found to be configurationally labile (Scheme 1B). [11] Therefore, angelic aldehyde was immediately used in a Still-Gennari olefination with 31 to give dienoate 32, which was then reduced to give allylic alcohol 20. [12,13] Sharpless asymmetric epoxidation of 20 proceeded in excellent yield to give 33, but with a modest 81 % ee, [15] as previously observed with Zconfigured allylic alcohols.…”

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Bioinspired Asymmetric Total Synthesis of Emeriones A–C**

Jänner

Isak

et al. 2022

Angewandte Chemie

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We report asymmetric bioinspired total syntheses of the fungal metabolites emeriones A-C via stereoselective oxidations of two bicyclo[4.2.0]octadiene diastereomers. The central bicyclic scaffolds are prepared in an 8π/6π electrocyclization cascade of a stereodefined pentaene, which contains the fully assembled side chains of the emeriones. The anti-aldol side chain is made using a Paterson-aldol addition, and the epoxide of the dioxabicyclo[3.1.0]hexane side chain via ring-closure onto an oxidized acetal. Our work has enabled the structural revision of emerione C, and resulted in the synthesis of a "missing" family member, which we call emerione D. DFT calculations identified two methyl groups that govern torquoselectivity in the 8π/6π cascade.Natural products derived from polyenes that undergo cyclization/isomerization cascades initiated by an 8π electrocyclization have intrigued chemists for decades. [1] The emeriones (Figure 1), one such family of natural products that were isolated from the fungus E. nidulans, [2] display oxidized bicyclo[4.2.0]octadiene cores (red) flanked by a seven carbon aldol fragment (blue) and a propenyl-substituted dioxabicyclo[3.1.0]hexane system (black). The two side chains (blue and black) of emerione A (1) and B (2) share the same absolute configurations, while the bicyclo-[4.2.0]octadieneoxide central scaffolds are enantiomeric with respect to each other. Emerione C has a bridging endoperoxide on the central core, and its proposed structure has a stereochemical configuration similar to emerione B.Related substances like shimalactone A (3) [1p] and ocellapyrone B (4) [1m, n] have been synthesized, but the emeriones are arguably the most complex examples of such natural products, each containing twelve stereocenters, eight of which are contiguous, and two quaternary. Moreover, the dioxabicyclo[3.1.0]hexane system, also found in natural products like verrucosidin (5), [3] is a considerable synthetic challenge alongside the oxidized bicyclo[4.2.0]octadiene scaffolds. Emerione A inhibits NO production in lipopolysaccharide-induced RAW264.7 cells [2] as well as NDM-1 [4] at low micromolar concentrations, but the emeriones appear not to have been tested in other assays. Motivated both by their striking structures and potentially undiscovered bioactivities, we chose to target the emeriones for synthesis. We describe herein the successful completion of the syntheses, the structural revision of emerione C, and the synthesis of the originally proposed structure of emerione C, which we name emerione D.

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Section: Figurementioning

confidence: 99%

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Bioinspired Asymmetric Total Synthesis of Emeriones A–C**

Jänner

Isak

et al. 2022

Angewandte Chemie

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“…After the esterification the installed allyl group was subjected to RCM (Scheme 20). [65] Building blocks for natural products Asymmetric synthesis of new polycyclic nitrogen containing compounds serving as valuable building blocks for a series of natural products has been accomplished in our group. In particular, the synthesized molecules present the isomeric scaffold of some alkaloids.…”

Section: Plant Natural Productsmentioning

confidence: 99%

Brown Allylation: Application to the Synthesis of Natural Products

et al. 2021

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Dedicated to Professor Franco Cozzi on the occasion of his 70th birthday.Asymmetric allylation represents an important reaction applied in the natural product synthesis. The stereoselective introduction of an allyl group allows to obtain versatile chiral building blocks, which may further undergo various transformations due to the presence of the carbon-carbon double bond. In this review, we address the Brown allylation, which involves the conversion of aldehydes into homoallylic alcohols using Ballyldiisopinocampheylborane as a chiral reagent. We provide a comprehensive overview of the reaction and highlight its application in the synthesis of natural products, while assessing its performance in comparison to other approaches. The total of 17 syntheses have been described, including the synthesis of biologically active macrolides disciformycin B, biselyngbyolide B, peloruside A, and gliomasolide A, bis-piperidine alkaloid (À )anaferine and dysoxylactam A.

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“…The synthesis of iodide 12 began with two step conversion of methyl angelate (30) into angelic aldehyde, which was found to be configurationally labile (Scheme 1B). [10] Therefore, after preparation, it was always immediately used in a Still-Gennari olefination with phosphonate 31 to give dienoate 32, which was subsequently reduced with DIBAL to give allylic alcohol 20. [11][12] We were surprised that neither 32 nor 20 are previously described compounds.…”

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Bioinspired Asymmetric Total Synthesis of Emeriones A–C

Jänner

Isak

Miller

2022

Preprint

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We report an asymmetric bioinspired total synthesis of the fungal metabolites emeriones A–C via stereoselective late-stage epoxidation or endoperoxidation of two bicyclo[4.2.0]octadiene diastereomers. The central bicyclic scaffold is synthesized in an 8pi/6pi electrocyclization cascade of a stereodefined (E,E,Z,Z,E)-pentaene, which contains the fully assembled and unprotected side chains of the natural products. The pentaene is constructed convergently through Stille cross-coupling of two similarly complex polyenes. The anti-aldol side chain of the emeriones is made using a Paterson-aldol approach, and the epoxide of the dioxobicyclo[3.1.0] side chain is synthesized via an unusual ring-closure onto an oxidized para-methoxyphenyl acetal. Our total synthesis has enabled the revision of the structure of emerione C and the synthesis of a “missing” family member, which we hereby call emerione D.

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An RCM‐Based Total Synthesis of the Antibiotic Disciformycin B

Cited by 14 publications

References 34 publications

Bioinspired Asymmetric Total Synthesis of Emeriones A–C**

Bioinspired Asymmetric Total Synthesis of Emeriones A–C**

Brown Allylation: Application to the Synthesis of Natural Products

Bioinspired Asymmetric Total Synthesis of Emeriones A–C

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