scholarly journals Assessing the possibilities of designing a unified multistep continuous flow synthesis platform

2018 ◽  
Vol 14 ◽  
pp. 1917-1936 ◽  
Author(s):  
Mrityunjay K Sharma ◽  
Roopashri B Acharya ◽  
Chinmay A Shukla ◽  
Amol A Kulkarni
Keyword(s):  
Detailed Analysis ◽  
Continuous Flow ◽  
Next Generation ◽  
One Pot ◽  
Complex Molecules ◽  
Flow Synthesis ◽  
One Pot Synthesis ◽  
Wide Range ◽  
Line Separation

The multistep flow synthesis of complex molecules has gained momentum over the last few years. A wide range of reaction types and conditions have been integrated seamlessly on a single platform including in-line separation as well as monitoring. Beyond merely getting considered as ‘flow version’ of conventional ‘one-pot synthesis’, multistep flow synthesis has become the next generation tool for creating libraries of new molecules. Here we give a more ‘engineering’ look at the possibility of developing a ‘unified multistep flow synthesis platform’. A detailed analysis of various scenarios is presented considering 4 different classes of drugs already reported in the literature. The possible complexities that an automated and controlled platform needs to handle are also discussed in detail. Three different design approaches are proposed: (i) one molecule at a time, (ii) many molecules at a time and (iii) cybernetic approach. Each approach would lead to the effortless integration of different synthesis stages and also at different synthesis scales. While one may expect such a platform to operate like a ‘driverless car’ or a ‘robo chemist’ or a ‘transformer’, in reality, such an envisaged system would be much more complex than these examples.

Indium Bromide-catalyzed Unprecedented Hydrogenolysis: A Novel One-Pot Synthesis of Per-O-Acetylated β-carboxymethyl O and S-glycosides

2020 ◽  
Vol 24 (8) ◽  
pp. 900-908
Author(s):  
Ram Naresh Yadav ◽  
Amrendra K Singh ◽  
Bimal Banik
Keyword(s):  
Asymmetric Synthesis ◽  
Chiral Auxiliary ◽  
Bioactive Molecules ◽  
One Pot ◽  
Enantiomerically Pure ◽  
Stereoselective Glycosylation ◽  
One Pot Synthesis ◽  
Wide Range

Numerous O (oxa)- and S (thia)-glycosyl esters and their analogous glycosyl acids have been accomplished through stereoselective glycosylation of various peracetylated bromo sugar with benzyl glycolate using InBr3 as a glycosyl promotor followed by in situ hydrogenolysis of resulting glycosyl ester. A tandem glycosylating and hydrogenolytic activity of InBr3 has been successfully investigated in a one-pot procedure. The resulting synthetically valuable and virtually unexplored class of β-CMGL (glycosyl acids) could serve as an excellent potential chiral auxiliary in the asymmetric synthesis of a wide range of enantiomerically pure medicinally prevalent β-lactams and other bioactive molecules of diverse medicinal interest.

scholarly journals Continuous-Flow Synthesis of Thioureas, Enabled by Aqueous Polysulfide Solution

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 303
Author(s):  
András Gy. Németh ◽  
Renáta Szabó ◽  
György Orsy ◽  
István M. Mándity ◽  
György M. Keserű ◽  
...  
Keyword(s):  
Multicomponent Reaction ◽  
Continuous Flow ◽  
Flow Synthesis ◽  
Mild Conditions ◽  
Wide Range ◽  
Simple Filtration

We have developed the continuous-flow synthesis of thioureas in a multicomponent reaction starting from isocyanides, amidines, or amines and sulfur. The aqueous polysulfide solution enabled the application of sulfur under homogeneous and mild conditions. The crystallized products were isolated by simple filtration after the removal of the co-solvent, and the sulfur retained in the mother liquid. Presenting a wide range of thioureas synthesized by this procedure confirms the utility of the convenient continuous-flow application of sulfur.

scholarly journals Thioesters Provide a Robust Path to Prebiotic Peptides

2021 ◽  
Author(s):  
Moran Frenkel-Pinter ◽  
Marcos Bouza ◽  
Facundo M. Fernández ◽  
Luke J. Leman ◽  
Loren Dean Williams ◽  
...  
Keyword(s):  
Building Blocks ◽  
Peptide Bond ◽  
Side Reactions ◽  
Peptide Bond Formation ◽  
One Pot ◽  
Complex Molecules ◽  
Peptide Formation ◽  
Wide Range ◽  
Amide Exchange ◽  
Prebiotic Earth

The condensation of building blocks into oligomers and polymers was an early and important stage in the origins of life. High activation energies, unfavorable thermodynamics and side reactions are bottlenecks for abiotic formation of peptides. Thioesters are hypothesized to have played key roles in prebiotic chemistry on early Earth, serving as energy storing molecules, as synthetic intermediates, and as catalysts in the formation of more complex molecules, including polypeptides. However, all abiotic reactions reported thus far for peptide formation via thioester intermediates have relied on activated building blocks or condensing agents, which are of questionable prebiotic relevance. We report robust, plausible prebiotic reactions of mercaptoacids with amino acids that result in the formation of peptides and thiodepsipeptides, which contain both peptide and thioester bonds. Peptide bond formation proceeds by the condensation of mercaptoacids to form thioesters followed by thioester-amide exchange. Mercaptoacids catalyze thiodepsipeptides and peptide formation under a wide range of pH conditions and at mild temperatures. Our results offer the most robust one-pot pathway for peptide formation ever reported. These results support the hypothesis that thiodepsipeptides formed robustly on prebiotic Earth and were possible contributors to early chemical evolution.

Molybdenum-Mediated One-Pot Synthesis of Pyrazoles from Isoxazoles

Synthesis ◽  
2019 ◽  
Vol 51 (20) ◽  
pp. 3796-3804 ◽  
Author(s):  
Marine Rey ◽  
Stéphane Beaumont
Keyword(s):  
Bond Cleavage ◽  
Direct Synthesis ◽  
Molybdenum Complex ◽  
One Pot ◽  
One Pot Synthesis ◽  
Wide Range ◽  
Hydrolysis Of ◽  
Substituted Pyrazoles

A one-pot approach for the direct synthesis of substituted pyrazoles from isoxazoles is reported. The process involves isoxazole N–O bond cleavage mediated by a molybdenum complex, in situ hydrolysis of the resulting β-amino enone to the corresponding 1,3-diketone, followed by pyrazole formation in the presence of hydrazine or substituted hydrazine. Good to excellent yields and regioselectivities are obtained with nonsymmetric isoxazoles. By using readily available starting materials, a wide range of substituted pyrazoles may be synthesized by this method.

One-Pot Synthesis of Thiazolo[3,4-a]Quinoxalines from 1,2-Diamines, Aryl Isothiocyanates and Ethyl Bromopyruvate

2017 ◽  
Vol 41 (12) ◽  
pp. 712-714 ◽  
Author(s):  
Mohammad Piltan
Keyword(s):  
Chromatographic Separations ◽  
One Pot ◽  
One Pot Synthesis ◽  
Three Component Reaction ◽  
Wide Range ◽  
Quinoxaline Derivatives ◽  
First Time ◽  
Aryl Isothiocyanates ◽  
Ethyl Bromopyruvate

Some hitherto unreported thiazolo[3,4- a]quinoxaline derivatives have been synthesised in excellent yields via a one-pot, three-component reaction of benzene-1,2-diamines, ethyl bromopyruvate and aryl isothiocyanates in MeCN, for the first time. The protocol avoids the use of any catalysts or chromatographic separations and provides a wide range of novel thiazolo[3,4- a]quinoxalines.

scholarly journals High Yielding Flow Synthesis of a Macrocyclic Molecular Hinge

2021 ◽  
Author(s):  
Christopher Jones ◽  
Laurence J. Kershaw Cook ◽  
David Marquez-Gamez ◽  
Konstantin V. Luzyanin ◽  
Jonathan Steed ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Continuous Flow ◽  
Kinetic Studies ◽  
Molecular Machines ◽  
High Dilution ◽  
Fluoride Ions ◽  
One Pot ◽  
Flow Synthesis ◽  
Single Isomer ◽  
Molecular Hinge

ABSTRACT: Many molecular machines are built from modular components with well-defined motile capabilities, such as axles and wheels. Hinges are particularly useful, as they provide the minimum flexibility needed for a simple and pronounced conformational change. Compounds with multiple stable conformers are common, but molecular hinges almost exclusively operate via dihedral rotations rather than truly hinge-like clamping mechanisms. An ideal molecular hinge would better reproduce the behavior of hinged devices, such as gates and tweezers, while remaining soluble, scalable and synthetically versatile. Herein, we describe two isomeric macrocycles with clamp-like open and closed geometries, which crystallize as separate polymorphs but interconvert freely in solution. An unusual one-pot addition cyclization reaction was used to produce the macrocycles on a multigram scale from inexpensive reagents, without supramolecular templating or high-dilution conditions. Using mechanistic information from NMR kinetic studies and at-line mass spectrometry, we developed a semi-continuous flow synthesis with maximum conversions of 85-93% and over 80% selectivity for a single isomer. The macrocycles feature voids that are sterically protected from guests, including reactive species such as fluoride ions, and could therefore serve as chemically inert hinges for adaptive supramolecular receptors and flexible porous materials.

scholarly journals A Scalable, Combined-Batch, and Continuous-Flow Synthesis of a Bio-Inspired UV-B Absorber

2019 ◽  
Vol 72 (11) ◽  
pp. 860 ◽  
Author(s):  
Mark York ◽  
Karen E. Jarvis ◽  
Jamie A. Freemont ◽  
John H. Ryan ◽  
G. Paul Savage ◽  
...  
Keyword(s):  
Continuous Flow ◽  
Partial Reduction ◽  
One Pot ◽  
Flow Synthesis ◽  
Sample Throughput

A new, chromatography-free synthesis for the preparation of an experimental UV-B absorber is reported. A key step of the process is a one-pot partial reduction of a symmetrical imide with a sequential dehydration step. The synthesis uses several continuous-flow steps to increase sample throughput and was used to prepare sufficient material to support further testing activities in >99% purity.

Engineering multi-functional bacterial outer membrane vesicles as modular nanodevices for biosensing and bioimaging

2017 ◽  
Vol 53 (54) ◽  
pp. 7569-7572 ◽  
Author(s):  
Qi Chen ◽  
Sharon Rozovsky ◽  
Wilfred Chen
Keyword(s):  
Outer Membrane ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Signal Generation ◽  
Antigen Binding ◽  
One Pot ◽  
One Pot Synthesis ◽  
Wide Range ◽  
Bacterial Outer Membrane ◽  
Synthesis Approach

We report here a one-pot synthesis approach to engineer multi-functionalized OMV-based sensors for both antigen binding and signal generation. A virtually unlimited combination of capturing and reporting moieties can be created for a wide range of biosensing and bioimaging applications.

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