Asymmetric Total Synthesis Enables Discovery of Antibacterial Activity of Siladenoserinols A and H

Márquez-Cadena, Miguel Adrián; Ren, Jingyun; Ye, Wenkang; Qian, Pei‐Yuan; Tong, Rongbiao

doi:10.1021/acs.orglett.9b03857

Cited by 18 publications

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References 35 publications

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“…The biomass-derived furan starting materials coupled with reliable, scalable, and green protocols render AchR an ideal platform to devise synthetic strategies for a variety of bioactive natural products (Figure ). These AchR-based strategies are usually more efficient and more flexible than the related previous syntheses, as exemplified by our syntheses of (i) a series of 6,8-dioxabicyclo-[3.2.1]octane (6,8-DOBCO) complex natural products (Figure C) , and (ii) decahydroquinoline alkaloid lepadins (Figure F) . Additionally, the AchR-based strategy allowed us to address the synthetic challenge of diastereoselective construction of trans -2,6-tetrahydropyran present in many natural products , (i.e., musellarins, Figure B).…”

Section: Application Of Achmatowicz Rearrangement In Total Synthesis ...supporting

confidence: 71%

Achmatowicz Rearrangement-Inspired Development of Green Chemistry, Organic Methodology, and Total Synthesis of Natural Products

2022

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Metrics & MoreArticle Recommendations CONSPECTUS:The six-membered heterocycles containing oxygen and nitrogen (tetrahydropyrans, pyrans, piperidines) are among the most common heterocyclic structures ubiquitously present in bioactive molecules such as carbohydrates, smallmolecule drugs, and natural products. Chemical synthesis of fully functionalized pyrans and piperidines is a research theme of practical importance and scientific significance and, thus, has attracted continuous interest from synthetic chemists. Among the numerous synthetic approaches, Achmatowicz rearrangement (AchR) represents a general and unique strategy that uses biomass-derived furfuryl alcohols as the renewable starting material to obtain fully functionalized six-membered oxygen/nitrogen heterocycles, which provides golden opportunities for organic chemists to address various synthetic challenges. This Account summarizes our 10 years of work on exploiting AchR to address some challenges in organic synthesis ranging from green chemistry and organic methodology to the total synthesis of natural products. We enabled the sustainable and safe use of AchR in a small (academia) or large (industrial) scale by developing two generations of green approaches for AchR (oxone-halide and Fenton-halide), which largely eliminate the use of the most popular, but more toxic and expansive, NBS and m-CPBA. This triggered our intensive interest in developing new green chemistry for important organic reactions, in particular, halogenation/oxidation reactions involving reactive halogenating species with the aim of eliminating the use of commonly used toxic halogen agents such as elemental bromine, chlorine gas, and various N-haloamide reagents (NBS, NCS, and NIS). We successfully employed oxone-halide and Fenton-halide as green alternatives to several mechanistically related organic reactions including arene/alkene halogenation, oxidation or oxidative rearrangement of indoles, oxidation of alcohols/thioacetals, and oxidative halogenation of aldoximes for the in situ generation of nitrile oxide. These green reactions are expected to have a solid impact on the future of organic synthesis in academia and industries. We expanded the synthetic utility of AchR by exploring several new transformations of AchR products and developed a cascade reductive ring expansion, reductive deoxygenation/Heck−Matsuda arylation, palladium-catalyzed C-arylation, and regiodivergent [3 + 2] cycloaddition with 1,3-dicarbonyls. These methodologies offer a new avenue to fully functionalized six-membered heterocycles.The synthetic utility of AchR was demonstrated in our total synthesis of 28 natural products with a pyran/piperidine moiety. The AchR-based strategy endows the total synthesis with scalability, sustainability, and flexibility. The green and scalable approaches developed in our lab for AchR allow us to easily obtain decagrams of synthetically valuable pyrans and/or piperidines with low risk and low cost from biomass-derived furfuryl alcohol/aldehyde.

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Section: Application Of Achmatowicz Rearrangement In Total Synthesis ...supporting

confidence: 71%

Achmatowicz Rearrangement-Inspired Development of Green Chemistry, Organic Methodology, and Total Synthesis of Natural Products

2022

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“…Therefore, we devised a new method for the synthesis of 6-alkyl-3-hydroxy-2-pyrones with positional substitution identical to that in 6 (Scheme ). Inspired by our previous work on Achmatowicz rearrangement, we envisioned that Achmatowicz rearrangement of substituted furfuryl alcohols ( 7 ) could provide the requisite THP ring of 2-pyrones and that subsequent epoxidation, Wharton rearrangement, and double oxidation of the α-hydroxy lactol would deliver the desired 6-alkyl-3-hydroxy-2-pyrones ( 11 ). This new method was finally established after extensive efforts to identify the conditions for protection/deprotection and double oxidation of the resulting α-hydroxy lactol, which either decomposed (oxidative cleavage) or was mono-oxidized under many classical oxidation conditions.…”

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confidence: 99%

Asymmetric Total Syntheses of (+)-Penostatins A and C

2020

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Penostatins A and C are cytotoxic natural products that show promising selective inhibitory activity against PTP1B.Here the first asymmetric total syntheses of (+)-penostatins A and C are reported. Our strategy features (i) a new method for the synthesis of 6-alkyl-3-hydroxy-2-pyrones, (ii) a cascade involving the intramolecular Diels−Alder reaction of 2-pyrone and a retrohetero-Diels−Alder (decarboxylation) reaction, (iii) Ando−Horner−Wadsworth−Emmons olefination/lactonization, and (iv) selenoxide elimination. Our study confirmed the absolute configurations of penostatins A and C and laid the groundwork for further bioactivity studies.

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“…Tong, Qian, and co-workers described a second asymmetric synthesis of 15 in 2019 (see Table 1, formation of 19). 17 They also applied an HWE reaction for the construction of the ,-unsaturated ester moiety and included the synthesis of siladenoserinol H, which is a structural analogue, to test for antibacterial activity of this compound class. 120 Rhizoxin is a natural product produced by species of the bacterial genus Burkholderia.…”

Section: Scheme 30 Total Synthesis Of Siladenoserinol a 15 By Doi And Coworkersmentioning

confidence: 99%

Applications of the Horner–Wadsworth–Emmons Olefination in Modern Natural Product Synthesis

Roman¹,

Sauer²,

Beemelmanns³

2021

Synthesis

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Here, we have summarized more than 30 representative natural product syntheses published in 2015 to 2020 that employ one or more Horner-Wadsworth-Emmons (HWE) reactions. We comprehensively describe the applied phosphonate reagents, HWE reaction conditions and key steps of the total synthetic approaches. Our comprehensive review will support future synthetic approaches and serve as guideline to find the best HWE conditions for the most complicated natural products known

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Asymmetric Total Synthesis Enables Discovery of Antibacterial Activity of Siladenoserinols A and H

Cited by 18 publications

References 35 publications

Achmatowicz Rearrangement-Inspired Development of Green Chemistry, Organic Methodology, and Total Synthesis of Natural Products

Achmatowicz Rearrangement-Inspired Development of Green Chemistry, Organic Methodology, and Total Synthesis of Natural Products

Asymmetric Total Syntheses of (+)-Penostatins A and C

Applications of the Horner–Wadsworth–Emmons Olefination in Modern Natural Product Synthesis

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