The <i>N</i>-Acyliminium Pictet−Spengler Condensation as a Multicomponent Combinatorial Reaction on Solid Phase and Its Application to the Synthesis of Demethoxyfumitremorgin C Analogues

Wang, Haishan; Ganesan, A.

doi:10.1021/ol991030d

Cited by 114 publications

(73 citation statements)

References 11 publications

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“…The first truly solid-supported N-acyliminium ion-mediated Pictet-Spengler reaction was reported a year later by Wang and Ganesan in their synthesis of demethoxyfumitremorgin C analogues (Scheme 2). 15 The authors' strategy was based on the immobilization of tryptophan derivatives on the Wang resin. Sequential treatment of the N-terminal with aldehydes and then acid chlorides generated transient N-acyliminium ions for Pictet-Spengler cyclization by attack of the indole moiety, affording a mixture of cis-and trans-tetrahydro-b-carbolines (THBCs).…”

Section: Intramolecular Reactionsmentioning

confidence: 99%

N‐acyliminium intermediates in solid‐phase synthesis

et al. 2010

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N-Acyliminium ions are powerful intermediates in synthetic organic chemistry. Examples of their use are numerous in solution-phase synthesis, but there are unmerited few reports on these highly reactive electrophiles in solid-phase synthesis. The present review covers the literature to date and illustrates the methods used to generate N-acyliminium intermediates on solid support and their further elaboration to a range of pharmacologically interesting peptidomimetics, heterocycles, and other small molecules.

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Section: Intramolecular Reactionsmentioning

confidence: 99%

N‐acyliminium intermediates in solid‐phase synthesis

et al. 2010

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“…This is consistent with previous results indicating about a 1:1 cis/trans ratio during the solidphase Pictet-Spengler reaction, followed by epimerization of the cis isomer. [46] …”

Section: Synthesis Of Tetrahydro-b-carboline Derivativesmentioning

confidence: 99%

Old Molecules for New Receptors: Trp(Nps) Dipeptide Derivatives as Vanilloid TRPV1 Channel Blockers

et al. 2006

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The transient receptor potential vanilloid member 1 (TRPV1), an integrator of multiple pain-producing stimuli, is regarded nowadays as an important biological target for the discovery of novel analgesics. Here, we describe the first experimental evidence for the behavior of an old family of analgesic dipeptides, namely Xaa-Trp(Nps) and Trp(Nps)-Xaa (Xaa=Lys, Arg) derivatives, as potent TRPV1 channel blockers. We also report the synthesis and biological investigation of a series of new conformationally restricted Trp(Nps)-dipeptide derivatives with improved TRPV1/NMDA selectivity. Compound 15 b, which incorporates an N-terminal 2S-azetidine-derived Arg residue, was the most selective compound in this series. Collectively, a new family of TRPV1 channel blockers emerged from our results, although further modifications are required to fine-tune the potency/selectivity/toxicity balance.

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“…21,178 A similar solidphase approach has been described for the synthesis of demethoxyfumitremorgin (158a), the most active of this series of alkaloids, allowing the use of a larger variety of aldehydes for the Pictet-Spengler condensation with Nacyliminium species. 179 With the aim to generate libraries of potential activators and/or inhibitors of protein kinase C (PKC), 180,181 Waldmann and co-workers 182 established a methodology for the solidphase synthesis of analogues of (-)-indolactam V (163), a metabolite that possess the core structure of the tumor promoting teleocidins and has been recognised as a PKC activator. 180,183 Based on known structural requirements of indolactams to their binding ability to PKC, these authors have prepared a 31-membered library of analogues (166) with diversified substituents at C-12, C-7 and N-13 ( Figure 44).…”

Section: Alkaloidsmentioning

confidence: 99%

Natural Product‐Like Combinatorial Libraries

Abreu

Branco

2004

ChemInform

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A química combinatorial emergiu ao longo dos últimos anos como uma importante ferramenta na pesquisa de moléculas pioneiras para a modelagem de novos fármacos. Nesta perspectiva, a diversidade estrutural e a vasta gama de propriedades biológicas exibidas pelos metabolitos secundários, constituem um desafio à implementação de estratégias combinatórias na síntese e derivatização de produtos naturais. Este artigo ilustra a aplicação das técnicas combinatórias no desenho e formação de bibliotecas baseadas em produtos naturais de diversa origem biossintética, e seus análogos estruturais.Combinatorial chemistry has emerged over the last few years as an important tool for drug discovery and lead optimisation. In this approach, the molecular diversity and range of biological properties displayed by secondary metabolites constitutes a challenge to combinatorial strategies for natural products synthesis and derivatization. This article surveys the application of combinatorial techniques to the design of "natural product-looking" libraries covering a wide range of structural diversities.

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The N-Acyliminium Pictet−Spengler Condensation as a Multicomponent Combinatorial Reaction on Solid Phase and Its Application to the Synthesis of Demethoxyfumitremorgin C Analogues

Cited by 114 publications

References 11 publications

N‐acyliminium intermediates in solid‐phase synthesis

N‐acyliminium intermediates in solid‐phase synthesis

Old Molecules for New Receptors: Trp(Nps) Dipeptide Derivatives as Vanilloid TRPV1 Channel Blockers

Natural Product‐Like Combinatorial Libraries

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