Stereospecific Synthesis of <i>syn</i>-α-Oximinoamides by a Three-Component Reaction of Isocyanides, <i>syn</i>-Chlorooximes, and Carboxylic Acids

Pirali, Tracey; Mossetti, Riccardo; Galli, Simona; Tron, Gian Cesare

doi:10.1021/ol201397x

Cited by 30 publications

(16 citation statements)

References 40 publications

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“…The key step in the synthesis of isoxazole‐derived inhibitor 2b was Ru(II)‐catalyzed cycloaddition between alkyne 21 (see Scheme ) and N ‐hydroxybenzimidoyl chloride 34 (Scheme ) . The latter was obtained from 1‐bromo‐4‐ n ‐pentylbenzene in a reaction sequence comprising metallation with n ‐BuLi and quench of the transient aryllithium with DMF, subsequent condensation of the formed aldehyde 33 with hydroxylamine and chlorination of the intermediate oxime with NCS .…”

Section: Resultsmentioning

confidence: 99%

Azole‐based non‐peptidomimetic plasmepsin inhibitors

Kinena

Leitis

Kanepe

et al. 2018

Archiv der Pharmazie

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The spread of drug-resistant malaria parasites urges the search for new antimalarial drugs. Malarial aspartic proteases - plasmepsins (Plms) - are differentially expressed in multiple stages of the Plasmodium parasite's lifecycle and are considered as attractive drug targets. We report the development of novel azole-based non-peptidomimetic plasmepsin inhibitors that have been designed by bioisosteric substitution of the amide moiety in the Actelion amino-piperazine inhibitors. The best triazole-based inhibitors show submicromolar potency toward Plm II, which is comparable to that of the parent Actelion compounds. The new inhibitors can be used as a starting point for the development of a resistance-free antimalarial drug targeting the non-digestive Plm IX or X, which are essential for the malaria parasite life cycle.

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Section: Resultsmentioning

confidence: 99%

Azole‐based non‐peptidomimetic plasmepsin inhibitors

Kinena

Leitis

Kanepe

et al. 2018

Archiv der Pharmazie

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“…To our surprise, no reaction occurred when pyridine, quinoline, t-butyl isocyanide, and 1,1,3,3-tetramethylbutyl isocyanide were used under similar reaction conditions. Characterization of all the synthesized compounds was done by IR, 1 H NMR, 13 C NMR, and mass in agreement with the proposed structures. The 1 H NMR spectra of all compounds showed several signals about at d = 0.80-2.00 (CH 2 ) and 3.00-4.80 (CH) corresponding to cyclohexyl ring that confirmed the presence of two-molecule cyclohexyl isocyanide in the structures.…”

Section: Resultsmentioning

confidence: 78%

“…Mechanistically, the reaction may be considered to proceed via the initial formation of the nitrile N-oxide 6 from the reaction between isoquinoline and chlorooxime 3 [13,14]. This intermediate is intercepted by the carbon of cyclohexyl isocyanide to give 7.…”

Section: Resultsmentioning

confidence: 99%

A diastereoselective synthesis of (Z)-3-[(aryl)(hydroxyimino)methyl]-2-cyclohexyl-1-(cyclohexylamino)imidazo[5,1-a]isoquinolinium chlorides from isoquinoline, chlorooximes, and cyclohexyl isocyanide

Khalili

2015

Monatsh Chem

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“…The tactic to expand the scope of Passerini reaction was to use surrogates of the carbonyl partners. As described in Scheme , syn ‐chlorooximes, diazoketones, alcohols, azirines and isatins could be employed instead of aryl or alkyl aldehydes (Scheme ). Besides, in 2018, Zhang and co‐workers have firstly reported asymmetric phosphoric acid‐catalyzed four‐component Ugi reaction, which solved the long‐standing stereochemical challenges of the Ugi reaction.…”

Section: Electrophilic Acidsmentioning

confidence: 99%

Arylacetic Acids in Organic Synthesis

et al. 2019

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Arylacetic acids are widely used in organic reactions and their recent advances are summarized in six categories according to their triggered pathways: (1) the acid as directing group in ortho-or meta-CÀ H activation; (2) decarboxylation; (3) deprotonation; (4) nucleophilic methylenes; (5) nucleophilic acids; (6) electrophilic acids. Reactions with alkenes, alkynes, aldehydes, amines, water, Grignard reagents, silanes and so forth are discussed. We hope this Minireview will promote future research in this area. Recently, the Zeng group [3g] reported a weakly coordinationassisted alkynylation of arylacetic acids with iridium catalysis under air atmosphere (Eq. 2-2). It was supported the sixmembered ring cycloiridiated 2.5 acted as the key intermediate. The alkynylation of indole, thiophene, pyrrole, and benzo[b] thiophene afforded better yields than phenylacetic acids. The acid moiety could also participated in the intramolecular ortho-CÀ H activation, which was developed by the Shi group to obtain lactonization 2.6 (Eq. 2-3) (Scheme 2). Meta-CÀ H ArylationThe study of Yu group [3e] in 2017 revealed a successful control of meta selectivity 3.1 of arylation from aryl iodides (Eq. 3-1). The use of mono-protected 3-amino-2-hydroxypyridine (as ligand) and 2-carbomethoxynorbornene (NBE-CO 2 Me) were crucial. In the absence of NBE-CO 2 Me, only ortho-arylated product was obtained. This method was still efficient in a gramsale (Scheme 3). Decarboxylation Decarboxylative CouplingAs shown in Scheme 4, the decarboxylation could generate benzyl radicals 4.1. Then, direct couplings of 4.1 with diverse [ + ] These authors contributed equally. Scheme 1. Six categories based on triggered mechanism. 2 3 4 5 6 7 8 . Passerini Three-Component ReactionThe Passerini reaction was the oldest multicomponent reaction (MCR) [37d] in which isocyanides, carboxylic acids and aldehydes were used. It was powerful for the rapid construction of complex molecules. The tactic to expand the scope of Passerini reaction was to use surrogates of the carbonyl partners. As described in Scheme 51, syn-chlorooximes, [37b] diazoketones, [37c] alcohols, [37d,e] azirines [37f] and isatins [37g] could be employed instead of aryl or alkyl aldehydes [37a] (Scheme 51). Besides, in 2018, Zhang and co-workers [37] have firstly reported asymmetric phosphoric acid-catalyzed four-component Ugi reaction, which Scheme 45. BTM-catalyzed cycloaddition. Scheme 46. HBTM-catalyzed cycloaddition. Scheme 47. TFA-catalyzed reaction. Scheme 48. Friedel-Crafts triggered tandem reactions. Scheme 49. C-acylation of 1,3-diones. Scheme 50. C-acylation of 1,3-indandiones.

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Stereospecific Synthesis of syn-α-Oximinoamides by a Three-Component Reaction of Isocyanides, syn-Chlorooximes, and Carboxylic Acids

Abstract: A stereospecific multicomponent reaction among isocyanides, syn-chlorooximes, and carboxylic acids provides an efficient synthesis of biologically relevant syn-α-oximinoamides.

Cited by 30 publications

References 40 publications

Azole‐based non‐peptidomimetic plasmepsin inhibitors

Azole‐based non‐peptidomimetic plasmepsin inhibitors

A diastereoselective synthesis of (Z)-3-[(aryl)(hydroxyimino)methyl]-2-cyclohexyl-1-(cyclohexylamino)imidazo[5,1-a]isoquinolinium chlorides from isoquinoline, chlorooximes, and cyclohexyl isocyanide

Arylacetic Acids in Organic Synthesis

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