Construction of Substituted <i>N</i>‐Hydroxyindoles: Synthesis of a Nocathiacin I Model System

Nicolaou, K. C.; Lee, Sang Hyup; Estrada, Anthony A.; Zak, Mark

doi:10.1002/anie.200500724

Cited by 57 publications

(52 citation statements)

References 17 publications

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“…The reaction seemed to be directed into an undesired pathway decreasing the speed of formation of 6a. This pathway involves nucleophilic attack of the nitrogen of the hydroxylamine intermediate 3a onto the carbonyl group of the pyruvate to form the hydroxyindole side product 5a prior to complete reduction of the hydroxylamine intermediate 3a into arylamine 4a [14]. This latter intermediate was never observed during this study presumably because of its high reactivity toward spontaneous cyclization giving the desired indole product 6a upon dehydration.…”

Section: Study Of the Mechanism And Chemoselectivity Of The Reissert mentioning

confidence: 81%

“…Subsequent catalytic reduction of the nitro group of ethyl o-nitrophenylpyruvate leads to spontaneous cyclization and formation of indole-2-carboxylic ester (Scheme 1). The reaction conditions remain strongly dependent on the nature of the chosen o-nitrotoluene substrates and the use of different alkylation conditions (NaH/ DMF [14], EtONa/EtOH [15], and neat DBU [16]) was necessary. Some ethyl o-nitrophenylpyruvate derivatives have therefore been obtained in moderate to good yields but none of these conditions proved to be sufficiently versatile to prepare a broad range of substrates.…”

Section: Study Of the Mechanism And Chemoselectivity Of The Reissert mentioning

confidence: 99%

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Reissert Indole Synthesis Using Continuous-Flow Hydrogenation

et al. 2011

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A series of substituted indole-2-carboxylic acid ethyl esters and aza-indole analogs have been prepared using continuous-flow hydrogenation. The identification of some key parameters using a design of experiments (DoE)-based approach allowed efficient optimization of each synthesis. The scale-up study for the multigram preparation of one model indole substrate showed the importance of working at steady state with the H-Cube apparatus. A new useful method for the easy preparation of substituted indoles in various quantities is presented.

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Section: Study Of the Mechanism And Chemoselectivity Of The Reissert mentioning

confidence: 81%

Section: Study Of the Mechanism And Chemoselectivity Of The Reissert mentioning

confidence: 99%

Reissert Indole Synthesis Using Continuous-Flow Hydrogenation

et al. 2011

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“…[94] A new synthesis of N-hydroxyindoles 121 by reduction of the nitro compounds 120 has recently been reported as part of model studies towards the nocathiacins (Scheme 28). [95] …”

Section: Indolesmentioning

confidence: 97%

From Amino Acids to Heteroaromatics—Thiopeptide Antibiotics, Nature's Heterocyclic Peptides

2007

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Amino acids, the building blocks of proteins, also serve as precursors to a wide range of other naturally occurring substances including alkaloids, antibiotics, and, the subject of this Review, heterocyclic peptides. Simple alpha-amino acids are converted into complex arrays of heteroaromatic rings that display interesting and potent biological activity. The thiopeptide antibiotics, with their complex molecular architectures, are wonderful examples. In this Review we show how organic chemists have developed innovative methods for the synthesis of the heterocyclic ring systems, including routes inspired by the likely biosynthetic processes, and successfully assembled such building blocks into the final target molecule by application of orthogonal protecting groups and coupling methodologies.

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“…Recently, we reported the synthesis of 1-hydroxyindole-2-carboxylates, [16][17][18][19][20] and 1-hydroxy-2-phenylindoles 21,22 with a limited number of derivatives. These initial successes prompted us to expand our studies for the construction of diverse derivatives.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of new 3-[(alkylthio)methyl]-1-hydroxy-2-(4'-substituted phenyl)indoles and their mechanistic studies on substituent effects

Cho¹,

Kim²,

Lim³

et al. 2017

Arkivoc

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The synthesis and mechanistic studies of new 3-[(alkylthio)methyl]-1-hydroxy-2-(4'-substituted phenyl)indoles 1 were presented. New substrates 2 were prepared by the application of efficient three-step synthesis with minor modifications, and used to produce target 1-hydroxyindoles 1. Substrates 2 were reacted with thiol nucleophiles in the presence of SnCl2·2H2O and 4Å molecular sieves to afford sixteen novel 1-hydroxyindoles 1, by a consecutive process involving nitro reduction, intramolecular cyclization, and nucleophilic 1,5-addition. Studies on the mechanistic aspects of these reactions with focus on the effects of p-substituent (X) in phenyl ring at C(1) in 2 were performed.

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Construction of Substituted N‐Hydroxyindoles: Synthesis of a Nocathiacin I Model System

Abstract: Generation (1→2) and trapping (2→3) of the fleeting α,β‐unsaturated nitrone system 2 leads to the rare, biologically important N‐hydroxyindole 3 in synthetically useful yields. This structural motif is found within the molecule of the antibiotic nocathiacin I.

Cited by 57 publications

References 17 publications

Reissert Indole Synthesis Using Continuous-Flow Hydrogenation

Reissert Indole Synthesis Using Continuous-Flow Hydrogenation

From Amino Acids to Heteroaromatics—Thiopeptide Antibiotics, Nature's Heterocyclic Peptides

Synthesis of new 3-[(alkylthio)methyl]-1-hydroxy-2-(4'-substituted phenyl)indoles and their mechanistic studies on substituent effects

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