The Chemistry of Oxindole.

Sumpter, Ward C.

doi:10.1021/cr60118a003

Cited by 62 publications

(18 citation statements)

References 99 publications

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“…[25] Indoles are regarded as one of the privileged skeletons in bioactive compounds, thus the combination of an indole and a dihydropyranone motif in one molecule will be interesting not only to synthetic but also to medicinal chemists. [26] It was found that the reaction conditions of tri-A C H T U N G T R E N N U N G fluoromethyl ketones were also good for isatins, except that 1.5 equivalents of acyl chloride were required for full consumption of isatins 7, and a reaction temperature of À40 8C instead of À78 8C was applied to make the reaction go smoothly in most cases. The reaction of isatin 7a reacted well with acyl chlorides 1a, 1c, 1e, 1f, 1g and lj, with either phenyl, 4-bromophenyl, 4-methylphenyl, 4-methoxylphenyl, 3-chlorophenyl or 2-thienyl substituents, to give the spirocyclic product 8 in moderate to good yield with good to high enantioselectivity (entries 1-6).…”

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N‐Heterocyclic Carbene‐Catalyzed Cyclization of Unsaturated Acyl Chlorides and Ketones

2011

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A straightforward synthesis of optically active trifluoromethyl dihydropyranones and spirocyclic oxindole-dihydropyranones has been realized by the chiral N-heterocyclic carbenes-catalyzed cy-A C H T U N G T R E N N U N G clization of a,b-unsaturated b-methylacyl chlorides with activated trifluoromethyl ketones or isatin derivatives.Keywords: asymmetric catalysis; cyclization; dihy-A C H T U N G T R E N N U N G dropyranones; N-heterocyclic carbenes; organocatalysis; vinylketenes Since Staudingers discovery of ketenes and the cycloaddition of ketene with imines to form b-lactams in early 1900s, [1] the cycloaddition reactions of ketene have become one of the powerful methodologies for construction of cyclic compounds.[2] In last decades, the catalytic enantioselective [2 + 2] or [2 + 4] cycloaddition of ketenes with aldehydes, [3] imines, [4] azo compounds, [5] nitro compounds, [6] oxadienes, [7] and azadienes [8] had been well established. In 2008 and later, we, [9] independently with Smith et al., [10] have demonstrated that N-heterocyclic carbenes (NHCs) [11] were efficient catalysts for the formal cycloaddition reactions of ketenes. The enolates I generated by the addition of NHC to ketenes are considered as the key intermediate for these reaction [Scheme 1, reaction (a)]. We conjecture that vinyl enolates II will be generated if vinylketenes are employed instead of ketenes, thus opening a new possibility of NHC-catalyzed reaction of vinylketenes [Scheme 1, reaction (b)].A literature survey revealed that Peters et al. reported a pioneering asymmetric Cinchona alkaloidscatalyzed cyclization of unsaturated acyl halides with aldehydes (Scheme 2). [12] In this paper, we wish to report an N-heterocyclic carbene-catalyzed cyclization of unsaturated acyl chlorides with activated ketones, which did not work when Cinchona alkaloids were used as the catalysts.[13]5,6-Dihydropyran-2-ones (a,b-unsaturated d-lactones) are widely present in a number of natural and unnatural compounds which possess potent biological Scheme 1. NHC-catalyzed cycloadditions of ketenes and vinylketenes.Scheme 2. Cinchona alkaloids-catalyzed annulation of unsaturated acyl chlorides by Peters et al.

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N‐Heterocyclic Carbene‐Catalyzed Cyclization of Unsaturated Acyl Chlorides and Ketones

2011

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“…Buchwald-Hartwing cross coupling was utilized to synthesize the N-aryl derivatives (27)(28)(29)(30). Two condensation products 24-25 were also synthesized via Knoevenagel condensation of the corresponding aldehydes (31,32) with oxindole, which in turn was prepared by the one-pot Wolff-Kishner like reduction in isatin with hydrazine hydrate (33,34). All the synthesized compounds (Table 1) The characterized isatin derivatives were then subjected to MTB CM enzyme inhibition study by adapting a previously reported protocol (5) to a 96-well plate format, as detailed in the experimental section of supporting information (Appendix S1) and the IC 50 values reported in Table 1.…”

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Discovery and Structure Optimization of a Series of Isatin Derivatives as Mycobacterium tuberculosis Chorismate Mutase Inhibitors

et al. 2014

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In this study, the crystal structure of the Mycobacterium tuberculosis (MTB) enzyme chorismate mutase (CM) bound to transition state analogue (PDB: 2FP2) was used as a framework for virtual screening of the BITS-Pilani in-house database (2500 compounds) to identify new scaffold. We identified isatin as novel small molecule MTB CM inhibitors; further twenty-four isatin derivatives were synthesized and evaluated in vitro for their ability to inhibit MTB CM, and activity against M. tuberculosis as steps towards the derivation of structure-activity relationships (SAR) and lead optimization. Compound 3-(4-nitrobenzylidene)indolin-2-one, 24 emerged as the most promising lead with an IC50 of 1.01 ± 0.22 μm for purified CM and MIC of 23.5 μm for M. tuberculosis, with little or no cytotoxicity.

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“…[1] As a subtype, spirocyclic oxindoles are of great interest and have been reported. Among them, the synthesis, synthetic application and bioactivity of spirocyclic oxindole-oxiranes [2] and oxindole-g-lactones [3] have been well-documented ( Figure 1).…”

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“…[b] Total yield of isolated the trans-and cis-isomers. [c] Determined by 1 H NMR of the reaction mixture. [d] The ee of trans-isomer followed by that of cis-isomer.…”

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Enantioselective Synthesis of Spirocyclic Oxindole‐β‐lactones via N‐Heterocyclic Carbene‐Catalyzed Cycloaddition of Ketenes and Isatins

2010

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Chiral N-heterocyclic carbenes were found to be efficient catalysts for the formal [2 + 2] cycloaddition reaction of disubstituted ketenes and isatins to give the corresponding spirocyclic oxindole-b-lactones in good yields with good diastereoselectivities and excellent enantioselectivities. Ring opening with Grignard reagents or decarboxylation of the oxindole spirocyclic-b-lactone gave the corresponding 3-hydroxy-or 3-alkylenyloxindoles in good yields.

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The Chemistry of Oxindole.

Cited by 62 publications

References 99 publications

N‐Heterocyclic Carbene‐Catalyzed Cyclization of Unsaturated Acyl Chlorides and Ketones

N‐Heterocyclic Carbene‐Catalyzed Cyclization of Unsaturated Acyl Chlorides and Ketones

Discovery and Structure Optimization of a Series of Isatin Derivatives as Mycobacterium tuberculosis Chorismate Mutase Inhibitors

Enantioselective Synthesis of Spirocyclic Oxindole‐β‐lactones via N‐Heterocyclic Carbene‐Catalyzed Cycloaddition of Ketenes and Isatins

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