A New Flow Methodology for the Expedient Synthesis of Drug‐Like 3‐Aminoindolizines

Bogdan, Andrew R.; James, K.

doi:10.1002/adsc.201200316

Cited by 34 publications

(11 citation statements)

References 35 publications

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“…Automated liquid dispensing systems can be used to create liquid droplets of different compositions which are transported through a tube like a conveyor belt of individual batch reactors. Though droplet methods have been used before to screen 39 and to generate libraries of compounds, 40 they have yet to be coupled with on-line sampling and nonlinear, mixed integer software optimization to give a tool capable of rapidly and automatically optimizing for all variables-continuous and discrete-of interest to a synthetic chemist.…”

Section: Workup Componentsmentioning

confidence: 99%

Tools for chemical synthesis in microsystems

2014

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Chemical synthesis in microsystems has evolved from simple proof-of-principle examples to become a general technique in academia and industry. Numerous such "flow chemistry" applications are now found in pharmaceutical and fine chemical synthesis. Much of the development has been based on systems employing macroscopic flow components and tubes, rather than the integrated chip technology envisioned by the lab-on-a-chip community. We review the major developments in systems for flow chemistry and discuss limitations underlying the development of chip-scale integrated systems.

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Section: Workup Componentsmentioning

confidence: 99%

Tools for chemical synthesis in microsystems

2014

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“…The respective nicotinamide derivatives were synthesized on the basis of a procedure described in the literature [ 31 ]. Piperazine was protected either with benzoyl or sulfonyl chloride, corresponding to secondary amine precursors “a’” and “b’”, which were used in the following reactions ( Scheme 2 ).…”

Section: Resultsmentioning

confidence: 99%

“…It was then coupled with 3,3 -diethoxy-propyne under Sonogashira reaction conditions, with subsequent ring-closing by the molybdenum complex, resulting in the targeted fluorescent pentathiepin derivative 1 as a red solid in 18% isolated yield after column chromatography purification (35% EtOAc/hexane) (Scheme 1). The purified sample was characterized by 1 The respective nicotinamide derivatives were synthesized on the basis of a procedure described in the literature [31]. Piperazine was protected either with benzoyl or sulfonyl chloride, corresponding to secondary amine precursors "a'" and "b'", which were used in the following reactions (Scheme 2).…”

Section: Resultsmentioning

confidence: 99%

Comprehensive Evaluation of Biological Effects of Pentathiepins on Various Human Cancer Cell Lines and Insights into Their Mode of Action

Wolff

Bandaru

Eger

et al. 2021

IJMS

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Pentathiepins are polysulfur-containing compounds that exert antiproliferative and cytotoxic activity in cancer cells, induce oxidative stress and apoptosis, and inhibit glutathione peroxidase (GPx1). This renders them promising candidates for anticancer drug development. However, the biological effects and how they intertwine have not yet been systematically assessed in diverse cancer cell lines. In this study, six novel pentathiepins were synthesized to suit particular requirements such as fluorescent properties or improved water solubility. Structural elucidation by X-ray crystallography was successful for three derivatives. All six underwent extensive biological evaluation in 14 human cancer cell lines. These studies included investigating the inhibition of GPx1 and cell proliferation, cytotoxicity, and the induction of ROS and DNA strand breaks. Furthermore, selected hallmarks of apoptosis and the impact on cell cycle progression were studied. All six pentathiepins exerted high cytotoxic and antiproliferative activity, while five also strongly inhibited GPx1. There is a clear connection between the potential to provoke oxidative stress and damage to DNA in the form of single- and double-strand breaks. Additionally, these studies support apoptosis but not ferroptosis as the mechanism of cell death in some of the cell lines. As the various pentathiepins give rise to different biological responses, modulation of the biological effects depends on the distinct chemical structures fused to the sulfur ring. This may allow for an optimization of the anticancer activity of pentathiepins in the future.

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“…Similar conditions were also effective in the preparation of indolizines using flow chemistry. [155] A very effective two-component palladium-catalyzed arylation/cyclization cascade protocol toward fused indolizines 105 has been developed by using propargyl-containing pyridines and aryl halides (Scheme 76). It was suggested that the palladium species, prepared via an oxidative addition of halides to palladium(0), activates the carbon-carbon triple bond to pyridyl nitrogen nucleophilic attack, forming the zwitterionic adduct.…”

Section: Palladium-catalyzed Synthesis Of Indolizinesmentioning

confidence: 99%

Recent Developments in the Cyclization of Alkynes and Nitrogen Compounds for the Synthesis of Indole Derivatives

Neto

Zeni

2021

Asian J Org Chem

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This review is intended to highlight the most useful approaches for the synthesis of indole derivatives (azaindoles, carbazoles, carbolines, indazoles, 3H-indoles, indolines, indolizines, isoindoles, and isoindolines), which were described by using transition-metal catalyzed cyclization reactions of alkynes and nitrogen compounds. The methodologies carried out under metal-free conditions will also be illustrated herein. This review will cover the data published mostly in the past decade. Synthesis of 6-AzaindolesAzaindoles, although rare in nature, have attracted a significant attention because some synthetic structures containing this nucleus exhibit biological activities. [17] The synthetic methods describing the preparation of azaindoles are limited. Usually their synthesis was achieved from the cyclization reaction of substrates containing aminopyridines. [18] Transition Metal-Free Synthesis of 6-AzaindolesWe have nominated two methodologies for the preparation of 6-azaindoles, which were developed using alkynes and nitrogen compounds in a metal-free protocol. In the first, an electrophilic cyclization condition, using iodine as an electrophilic source, was applied to 2-(azidomethyl)-3-alkynyl-pyrroles in the preparation of 4-iodo-6-azaindoles 1 (Scheme 1, eq 1). [19] The second approach described the preparation of 2,5-disubstituted 6azaindoles 2 from base-catalyzed intramolecular cyclization of 2-(azidomethyl)-3-alkynyl-pyrroles (Scheme 1, eq 2). [20] 3. Synthesis of 7-Azaindoles Transition Metal-Catalyzed Synthesis of 7-Azaindoles Silver-Catalyzed Synthesis of 7-AzaindolesSilver-catalyzed cyclization reactions of alkynes constitute powerful strategies for the construction of heterocycles. In particular, the 7-azaindoles could be obtained by these approaches. A general method for the preparation of aryl-[a] Dr. J.

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A New Flow Methodology for the Expedient Synthesis of Drug‐Like 3‐Aminoindolizines

Cited by 34 publications

References 35 publications

Tools for chemical synthesis in microsystems

Tools for chemical synthesis in microsystems

Comprehensive Evaluation of Biological Effects of Pentathiepins on Various Human Cancer Cell Lines and Insights into Their Mode of Action

Recent Developments in the Cyclization of Alkynes and Nitrogen Compounds for the Synthesis of Indole Derivatives

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