Base-Promoted Transannulation of Heterocyclic Enamines and 2,3-Epoxypropan-1-ones: Regio- and Stereoselective Synthesis of Fused Pyridines and Pyrroles

Zheng, Yang; Hao, Wen‐Juan; Xu, Haiwei; Wang, Shuliang; Jiang, Bo; Li, Guigen

doi:10.1021/acs.joc.5b00067

Cited by 20 publications

(3 citation statements)

References 39 publications

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“…In fact, the only tetronamide known to occur in nature is basidalin ( 2 ), an antitumor antibiotic isolated from terrestrial fungi . Synthetic tetronamides are frequently used as building blocks for the construction of complex molecules, as well as in chemical, medicinal and agrochemical research . Many such compounds possess significant antibacterial (e.g.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of new tetronamides displaying inhibitory activity against bloom‐forming cyanobacteria

Acosta

Karak

Barbosa

et al. 2019

Pest Management Science

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BACKGROUND: The increasing frequency and intensity of cyanobacterial blooms pose a serious threat to aquatic ecosystems. These blooms produce potent toxins that can contaminate drinking water and endanger the life of wild and domestic animals as well as humans. Consequently, the development of effective methods for their control is a matter of high priority. We have previously shown that some -benzylidenebutenolides, related to the rubrolide family of natural products, are capable of inhibiting the photosynthetic electron transport chain (Hill reaction), a target of commercial herbicides. Here we report the synthesis and biological properties of a new class of rubrolide-inspired molecules featuring a tetronamide motif.RESULTS: A total of 47 N-aryl tetronamides, including 38 aldol adducts, were prepared bearing phenyl, biphenyl, naphthyl, aliphatic and heteroaromatic groups. Some of the aldol adducts were dehydrated to the corresponding -benzylidenetetronamides, although satisfactory yields were obtained in only three cases (52-97%). None of the synthesized compounds were capable of blocking the Hill reaction. This notwithstanding, several aldol adducts equipped with a biphenyl substituent displayed excellent inhibitory activity against Synechococcus elongatus and other cyanobacterial strains (IC 50 = 1-5 M). Further, these tetronamides were found to be essentially inactive against eukaryotic microorganisms. CONCLUSION: Several newly synthesized biphenyl-containing tetronamides were shown to display potent and selective inhibitory activity against cyanobacteria. These compounds appear to exert their biological effects without interfering with the Hill reaction. As such, they represent novel leads in the search of environmentally benign agents for controlling cyanobacterial blooms.

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Section: Introductionmentioning

confidence: 99%

Synthesis of new tetronamides displaying inhibitory activity against bloom‐forming cyanobacteria

Acosta

Karak

Barbosa

et al. 2019

Pest Management Science

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“…Compounds containing the 4-aminofuran-2(5 H )-one scaffold, commonly known as tetronamides (Figure , I ), include the natural product basidalin ( III ) − and various synthetic molecules − (e.g., II and IV ), which are considered important templates for the development of agrochemicals , and pharmaceuticals − Because of the diverse biological properties of tetronamides, extensive studies of the synthesis of both chiral and achiral derivatives of such compounds have been conducted in recent years. − …”

Section: Introductionmentioning

confidence: 99%

Substituent-Modulated Conformation and Supramolecular Assembly of Tetronamides

Karak

Acosta

Barbosa

et al. 2016

Crystal Growth & Design

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The crystal structures of nine compounds (1−9) bearing the 4-aminofuran-2(5H)-one scaffold (commonly known as tetronamide, C 4 H 5 NO 2) and two decorating aromatic/ heteroaromatic moieties with two stereocenters have been determined. Tetronamides bearing at the 5-position a phenyl moiety (1 and 2, 3-chloro derivatives with either a 4-p-tolylamino or 4-p-bromophenylamino substituent), an o-bromopyridyl moiety (3, a 3-bromo-4-p-tolylamino derivative), or an o-tolyl moiety (4, a 3-bromo-4-p-tolylamino derivative) adopt a U-shaped conformation. This conformation is stabilized by an intramolecular contact involving either the phenyl o-CH moiety (1 and 2) or the substituent at the ortho position (3 and 4) and the π system of the N-phenyl ring. The other five tetronamides (5−9) are not present with such an intramolecular contact. In fact, these last five compounds are not U-shaped and feature the presence at the 5-position of a p-biphenyl moiety (5 and 7, 3-bromo-4-p-tolylamino diastereomers differing as 5R and 5S), a p-methoxyphenyl moiety (6, a 3-chloro-4-pbromophenylamino derivative), or a 5-chlorofuran-2-yl moiety (8 and 9, 3-chloro-4-p-tolylamino diastereomers differing as 5R and 5S). Crystal structures of a 5,5-disubstituted tetronamide bearing m-nitrophenyl moieties (10) and a parent tetronamide without a substituent at the 5-position (11d) reinforce the conformational trend found in 1−9. Furthermore, OH•••O centrosymmetric dimers are formed only in the crystal structures of the U-shaped tetronamides. Chain motifs assembled through OH•••O and NH•••O hydrogen bonds are preferred in the line-shaped tetronamides. Furthermore, the conformer energies were calculated in both the gas and solution phases (B3LYP/6-31G*). The lowest-energy conformations feature an intramolecular N−H•••O hydrogen bond as in the crystal structure of 7. In the U-shaped tetronamides, the crystal structure conformations are similar to the third or fourth energetically ranked stable calculated conformer. Therefore, it is concluded that the substitution pattern in the U-shaped tetronamides allows for accessible secondary minimum-energy conformations that are easily adopted in the crystal structure as a result of their compatibility with the robust centrosymmetric O−H•••O dimer formation.

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“…Its unique tetronamide structure, including the Z- geometry of the formylmethylidene moiety, was firmly established by X-ray analysis . Notwithstanding the frequent use of tetronamides in chemical, pharmaceutical, and agrochemical research, − basidalin holds the prominent position of being the first, and to date only, tetronamide known to occur in Nature. In addition, 1 possesses antibacterial properties and significant antitumor activity against leukemia, , both in vitro (IC 50 = 0.11 μg/mL) and in vivo, dose-dependently prolonging the survival of mice inoculated with L1210 cells …”

mentioning

confidence: 99%

Total Synthesis of the Antitumor Antibiotic Basidalin

et al. 2016

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The first synthesis of the tetronamide antibiotic basidalin was accomplished in five steps and 39% overall yield from readily available 4-bromo-2-triisopropylsilyloxyfuran and 2-formyl-1,3-dithiane. Highlights include: (i) regio- and stereocontrolled assemblage of a pivotal (Z)-γ-ylidene-β-bromobutenolide intermediate by stereodirected vinylogous aldol condensation (SVAC), (ii) installation of the amino group via aza-Michael addition/elimination, and crucially (iii) facile access to basidalin by late-stage dithiane removal.

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Base-Promoted Transannulation of Heterocyclic Enamines and 2,3-Epoxypropan-1-ones: Regio- and Stereoselective Synthesis of Fused Pyridines and Pyrroles

Cited by 20 publications

References 39 publications

Synthesis of new tetronamides displaying inhibitory activity against bloom‐forming cyanobacteria

Synthesis of new tetronamides displaying inhibitory activity against bloom‐forming cyanobacteria

Substituent-Modulated Conformation and Supramolecular Assembly of Tetronamides

Total Synthesis of the Antitumor Antibiotic Basidalin

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