Transition-metal-catalyzed site-selective C7-functionalization of indoles: advancement and future prospects

Shah, Tariq; De, Prithwiraj; Pradhan, Sourav; Punniyamurthy, Tharmalingam

doi:10.1039/c8cc04116d

Cited by 122 publications

(36 citation statements)

References 92 publications

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“…In particular, C7‐functionalized indole scaffolds exhibit a number of antiviral activities such as inhibitors of SARS‐CoV, HIV‐1, influenza virus A/Hanfang/359/95 (H3N2), and HSV II . As a consequence, there is a continued high demand for general strategies that provide easy access to C7‐substituted indoles in a sustainable fashion . Major advances in C−H activation have been witnessed in recent years .…”

Section: Introductionmentioning

confidence: 99%

C7‐Indole Amidations and Alkenylations by Ruthenium(II) Catalysis

Choi¹,

Messinis²,

Ackermann³

2020

Angew Chem Int Ed

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C7−H‐functionalized indoles are ubiquitous structural units of biological and pharmaceutical compounds for numerous antiviral agents against SARS‐CoV or HIV‐1. Thus, achieving site‐selective functionalizations of the C7−H position of indoles, while discriminating among other bonds, is in high demand. Herein, we disclose site‐selective C7−H activations of indoles by ruthenium(II) biscarboxylate catalysis under mild conditions. Base‐assisted internal electrophilic‐type substitution C−H ruthenation by weak O‐coordination enabled the C7−H functionalization of indoles and offered a broad scope, including C−N and C−C bond formation. The versatile ruthenium‐catalyzed C7−H activations were characterized by gram‐scale syntheses and the traceless removal of the directing group, thus providing easy access to pharmaceutically relevant scaffolds. Detailed mechanistic studies through spectroscopic and spectrometric analyses shed light on the unique nature of the robust ruthenium catalysis for the functionalization of the C7−H position of indoles.

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Section: Introductionmentioning

confidence: 99%

C7‐Indole Amidations and Alkenylations by Ruthenium(II) Catalysis

Choi¹,

Messinis²,

Ackermann³

2020

Angew Chem Int Ed

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“…Among the limited methods to functionalize the benzene portion of indole, functionalization at C4 and C7 typically rely on coordination of the catalyst to specific directing groups installed on either C3 or N1, respectively [13][14][15]. However, this method suffers from low functional group tolerance and a limited substrate scope [14][15][16][17][18][19][20][21][22]. The few described methods for C5 and C6 indole functionalization provide limited functional group tolerance [19,23].…”

Section: Introductionmentioning

confidence: 99%

Indole C6 Functionalization of Tryprostatin B Using Prenyltransferase CdpNPT

et al. 2020

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Tryprostatin A and B are prenylated, tryptophan-containing, diketopiperazine natural products, displaying cytotoxic activity through different mechanisms of action. The presence of the 6-methoxy substituent on the indole moiety of tryprostatin A was shown to be essential for the dual inhibition of topoisomerase II and tubulin polymerization. However, the inability to perform late-stage modification of the indole ring has limited the structure–activity relationship studies of this class of natural products. Herein, we describe an efficient chemoenzymatic approach for the late-stage modification of tryprostatin B using a cyclic dipeptide N-prenyltransferase (CdpNPT) from Aspergillus fumigatus, which generates novel analogs functionalized with allylic, benzylic, heterocyclic, and diene moieties. Notably, this biocatalytic functionalizational study revealed high selectivity for the indole C6 position. Seven of the 11 structurally characterized analogs were exclusively C6-alkylated, and the remaining four contained predominant C6-regioisomers. Of the 24 accepted substrates, 10 provided >50% conversion and eight provided 20–50% conversion, with the remaining six giving <20% conversion under standard conditions. This study demonstrates that prenyltransferase-based late-stage diversification enables direct access to previously inaccessible natural product analogs.

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“…This intrinsic selectivity is conquered either by employing a bulky DG at N ‐site or blocking the C2 position or reducing it to indolines and then carrying out the regioselective C−H functionalization of the later, followed by late‐stage oxidation. Recently, our group presented a review article featuring all the aspects of C7 functionalization of indoles and their future prospects [3e] . Here we mainly focus the recent developments along with their mechanistic inputs and a succinct summary of the previously covered approaches.…”

Section: Functionalization Of C(7)−h Bondmentioning

confidence: 99%

Recent Advances in Metal‐catalyzed Alkylation, Alkenylation and Alkynylation of Indole/indoline Benzenoid Nucleus

Pradhan

Shah

et al. 2020

Chemistry An Asian Journal

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Selective editing of the benzenoid CÀ H bonds (C4À C7) in indoles/indolines has received great interest because functionalized indoles/indolines are featured in many marketed drugs and natural products. Transition-metalcatalyzed directed CÀ H functionalization has thus been developed to manipulate the benzenoid core through CÀ C and C-heteroatom bond formation. This review covers the recent advances in selective CÀ C bond forming reactions, alkylation, alkenylation and alkynylation, over the benzenoid ring (C4À C7) of indoles/indolines using metal catalysis.

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Transition-metal-catalyzed site-selective C7-functionalization of indoles: advancement and future prospects

Abstract: The advancement and future prospects of transition-metal-catalyzed auxiliary assisted regioselective C7-functionalization of indoles/indolines are covered in this article.

Cited by 122 publications

References 92 publications

C7‐Indole Amidations and Alkenylations by Ruthenium(II) Catalysis

C7‐Indole Amidations and Alkenylations by Ruthenium(II) Catalysis

Indole C6 Functionalization of Tryprostatin B Using Prenyltransferase CdpNPT

Recent Advances in Metal‐catalyzed Alkylation, Alkenylation and Alkynylation of Indole/indoline Benzenoid Nucleus

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