Synthesis of Novel N-Rich Polycyclic Skeletons Based on Azoles and Pyridines

Sharma, Sunil K.; Saha, Biswajit; Sawant, Devesh; Kundu, Bijoy

doi:10.1021/cc0700445

Cited by 60 publications

(38 citation statements)

References 26 publications

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“…Recently, the Pictet-Spengler reaction has been successfully extended to arylamine substrates [11][12][13][14][15][16][17]. These substrates are designed by replacing the aliphatic amine side chain attached to activated heterocycles, for example tryptamine (1), by aromatic amines [11].…”

Section: Resultsmentioning

confidence: 99%

“…These reactions are generally termed as modified Pictet-Spengler reaction [11]. This modifi-cation of the conventional reaction led to the synthesis of a polyheterocyclic skeleton that mimics the natural products [12][13][14][15][16][17]. The 6-endo cyclization is the rate-limiting step in the Pictet-Spengler reaction and electrophilicity of the imine is the driving force of the reaction [1].…”

Section: Introductionmentioning

confidence: 99%

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Pictet‐Spengler Reaction

2010

Comprehensive Organic Name Reactions and Reagents

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A practical, mild and efficient protocol for the Pictet-Spengler reaction catalyzed by cyanuric chloride (trichloro-1,3,5-triazine, TCT) is described. The 6-endo cyclization of tryptophan/tryptamine and modified Pictet-Spengler substrates with both electronwithdrawing and electron-donating aldehydes was carried out by using a catalytic amount of TCT (10 mol %) in DMSO under a nitrogen atmosphere. TCT catalyzed the Pictet-Spengler reaction involving electron-donating aldehydes in excellent yield. Thus, it has a distinct advantage over the existing methodologies where electron-donating aldehydes failed to undergo 6-endo cyclization. Our methodology provided broad substrate scope and diversity. This is indeed the first report of the use of TCT as a catalyst for the Pictet-Spengler reaction.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pictet‐Spengler Reaction

2010

Comprehensive Organic Name Reactions and Reagents

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“…On the other hand, arylamines linked to an activated aromatic nucleus, such as imidazole, might be treated with aldehydes to give imidazo-quinoxalines (n = 0) after DDQ oxidation [306] or triazabenzoazulenes (n = 1) [307] (Scheme 89). Several novel N-rich polycyclic skeletons have been synthesized by application of this P-S variation [308][309][310][311][312][313], for which we propose the name of aza-Pictet-Spengler. About these presences and more we may talk in the third Act.…”

Section: Conclusion: Drawing a Veil Over Act IImentioning

confidence: 99%

“…been synthesized by application of this P-S variation [308][309][310][311][312][313], for which we propose the name of aza-Pictet-Spengler. About these presences and more we may talk in the third Act.…”

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confidence: 99%

The Pictet-Spengler Reaction Updates Its Habits

et al. 2020

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The Pictet-Spengler reaction (P-S) is one of the most direct, efficient, and variable synthetic method for the construction of privileged pharmacophores such as tetrahydro-isoquinolines (THIQs), tetrahydro-β-carbolines (THBCs), and polyheterocyclic frameworks. In the lustro (five-year period) following its centenary birthday, the P-S reaction did not exit the stage but it came up again on limelight with new features. This review focuses on the interesting results achieved in this period (2011–2015), analyzing the versatility of this reaction. Classic P-S was reported in the total synthesis of complex alkaloids, in combination with chiral catalysts as well as for the generation of libraries of compounds in medicinal chemistry. The P-S has been used also in tandem reactions, with the sequences including ring closing metathesis, isomerization, Michael addition, and Gold- or Brønsted acid-catalyzed N-acyliminium cyclization. Moreover, the combination of P-S reaction with Ugi multicomponent reaction has been exploited for the construction of highly complex polycyclic architectures in few steps and high yields. The P-S reaction has also been successfully employed in solid-phase synthesis, affording products with different structures, including peptidomimetics, synthetic heterocycles, and natural compounds. Finally, the enzymatic version of P-S has been reported for biosynthesis, biotransformations, and bioconjugations.

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“…In the literature, several examples for this condensation reaction are given, differing in solvent, reaction time, and purification approach with a wide range in yield (20-86%) depending on the choice of reactants [21][22][23][24][25]. For the purpose of this study, ethanol and a reflux time of 22 h resulted in superior yield and purity of the product after crystallization compared to e.g.…”

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confidence: 99%

Synthesis of Four SIRT1 Activators Based on an Imidazo[1,2-b]thiazole Structure, in vitro Derived Metabolites and Deuterated Analogs

Höppner¹,

Schlörer²,

Schänzer³

et al. 2014

TOOCJ

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Abstract:The enzyme sirtuin 1 (SIRT1) is a major target for the treatment of various metabolic disorders. Herein, a practical synthesis of imidazo [1,2-b]thiazole derivatives, one of the most comprehensively studied class of synthetic SIRT1 activators, is presented. The synthesized SIRT1 activators, the in vitro-identified metabolite of SRT1720, and the eightfold deuterated analytical standards were obtained through a six-step protocol yielding model compounds with a conserved core structure and two variable moieties. A multiplicity of potential SIRT1 activators and metabolites can be prepared with substituents enabling the modification of biological effects.Keywords: Isotope labeling, metabolite, SIRT1 activator, SRT1720, SRT2104.The enzyme sirtuin 1 (SIRT1) is an important metabolic key regulator and therefore a promising target for the treatment of metabolic disorders such as type II diabetes mellitus [1,2]. Since the naturally occurring polyphenol resveratrol was discovered as a SIRT1 activator in 2003 [3] several new artificial SIRT1 activators were developed based on a common template exhibiting different substituents, some of which are exemplified in Fig. (1) [4].In this context, SIRT1 activators based on an imidazo[1,2-b]thiazole nucleus represent the best studied class of SIRT1 activators including SRT1720, SRT1460 and SRT2104, which were tested in several in vitro and in vivo studies within the last seven years [5][6][7]. Even though the *Address correspondence to this author at the Center for Preventive Doping Research/Institute of Biochemistry, German Sport University Cologne, Germany; Tel: +49 221 4982 7070; Fax: +49 221 4982 7071; E-mail: thevis@dshs-koeln.de activation of the enzyme SIRT1 by these low molecular mass compounds was controversially discussed [8][9][10][11][12], a variety of SIRT1 activators is at present undergoing preclinical and clinical studies (SRT2104 [13,14], SRT2379 [15,16] and SRT3025) concerning their utility in the treatment of metabolic, inflammatory and cardiovascular diseases. In addition to SIRT1 activators, the synthesis of metabolites and deuterated analogs of known activators (e.g. SRT1720) for mass spectrometric characterization and quantification is of great interest [17,18]. Therefore an alternative, efficient and simple route to synthesize SIRT1 activators (Fig. 2) based on an imidazo [1,2-b] thiazole structure (related to SRT1720 and SRT2104) (Fig. 1) is presented. Four SIRT1 activators and an in vitro observed hydroxy metabolite of SRT1720 (1b, 2a, 3a, 4a, 5a; Fig. 2) as well as the eightfold deuterated standards (6a), were synthesized by the procedure described in the following [19].The alternative synthesis employed a six-step reaction protocol utilizing intermediates (7, 9, 10a-b, Scheme 1) Fig. (1). Selected SIRT1 activators known from literature.

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Synthesis of Novel N-Rich Polycyclic Skeletons Based on Azoles and Pyridines

Abstract: An efficient method for the synthesis of new polycyclic skeletons: triaza-benzofluorenes and triaza-pentalenonaphthalene from bicyclic privileged structures imidazopyridine and imidazothiazole, respectively, has been described using the Pictet-Spengler cyclization.

Cited by 60 publications

References 26 publications

Pictet‐Spengler Reaction

Pictet‐Spengler Reaction

The Pictet-Spengler Reaction Updates Its Habits

Synthesis of Four SIRT1 Activators Based on an Imidazo[1,2-b]thiazole Structure, in vitro Derived Metabolites and Deuterated Analogs

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