Consecutive multicomponent reactions for the synthesis of complex molecules

2019 ◽  
Vol 17 (33) ◽  
pp. 7632-7650 ◽  
Author(s):  
Sanjun Zhi ◽  
Xiaoming Ma ◽  
Wei Zhang
Keyword(s):  
Multicomponent Reactions ◽  
Structural Diversity ◽  
Complex Molecules ◽  
Molecular Complexity ◽  
Synthetic Efficiency

Consecutive multicomponent reactions (MCRs) combine two or more MCRs to achieve high synthetic efficiency, product structural diversity, and molecular complexity.

scholarly journals 6’-Amino-5,7-Dibromo-2-Oxo-3’-(Trifluoromethyl)-1’H-Spiro[Indoline-3,4’-Pyrano[2,3-c]Pyrazole]-5’-Carbonitrile

Molbank ◽  
10.3390/m1309 ◽  
2021 ◽  
Vol 2022 (1) ◽  
pp. M1309
Author(s):  
Yuliya E. Ryzhkova ◽  
Varvara M. Kalashnikova ◽  
Michail N. Elinson
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Biological Activity ◽  
Infrared Spectroscopy ◽  
Sodium Acetate ◽  
Multicomponent Reactions ◽  
Structural Diversity ◽  
Synthetic Methods ◽  
Environmentally Benign ◽  
Complex Molecules ◽  
Synthetic Target

The multicomponent reactions are environmentally benign synthetic methods of building-up of complex molecules and several levels of structural diversity for diverse applications. Spirooxindoles are an important synthetic target possessing extended biological activity and drug discovery applications. In this communication, the multicomponent transformation of 5,7-dibromoisatin, malononitrile, and 5-(trifluoromethyl)-2,4-dihydro-3H-pyrazol-3-one in EtOH at reflux in the presence of sodium acetate was carefully investigated to give 6’-amino-5,7-dibromo-2-oxo-3’-(trifluoromethyl)-1’H-spiro[indoline-3,4’-pyrano[2,3-c]pyrazole]-5’-carbonitrile in excellent yield. The structure of the new compound was established by means of elemental analysis, mass and nuclear magnetic resonance, and infrared spectroscopy.

Metal-, and Organocatalyst-Free One-Pot Assembly of Chiral Aza-Tricyclic Molecules: Creating Six Contiguous Stereocenters from 2-D-Structures and an Amino Acid

2020 ◽  
Author(s):  
Dung Do
Keyword(s):  
Amino Acid ◽  
Chemical Space ◽  
Structural Diversity ◽  
Therapeutic Agents ◽  
Chiral Molecules ◽  
One Pot ◽  
Complex Molecules ◽  
Chiral Catalyst ◽  
Chiral Complex ◽  
Free Process

<p>Chiral molecules with their defined 3-D structures are of paramount importance for the study of chemical biology and drug discovery. Having rich structural diversity and unique stereoisomerism, chiral molecules offer a large chemical space that can be explored for the design of new therapeutic agents.<sup>1</sup> Practically, chiral architectures are usually prepared from organometallic and organocatalytic processes where a transition metal or an organocatalyst is tailor-made for desired reactions. As a result, developing a method that enables rapid assembly of chiral complex molecules under metal- and organocatalyst-free condition represents a daunting challenge. Here we developed a straightforward route to create a chiral 3-D structure from 2-D structures and an amino acid without any chiral catalyst. The center of this research is the design of a <a>special chiral spiroimidazolidinone cyclohexadienone intermediate</a>, a merger of a chiral reactive substrate with multiple nucleophillic/electrophillic sites and a transient organocatalyst. <a>This unique substrate-catalyst (“subcatalyst”) dual role of the intermediate enhances </a><a>the coordinational proximity of the chiral substrate and catalyst</a> in the key Aza-Michael/Michael cascade resulting in a substantial steric discrimination and an excellent overall diastereoselectivity. Whereas the “subcatalyst” (hidden catalyst) is not present in the reaction’s initial components, which renders a chiral catalyst-free process, it is strategically produced to promote sequential self-catalyzed reactions. The success of this methodology will pave the way for many efficient preparations of chiral complex molecules and aid for the quest to create next generation of therapeutic agents.</p>

scholarly journals Identifying molecules as biosignatures with assembly theory and mass spectrometry

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Stuart M. Marshall ◽  
Cole Mathis ◽  
Emma Carrick ◽  
Graham Keenan ◽  
Geoffrey J. T. Cooper ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
De Novo ◽  
Outer Space ◽  
Molecular Assembly ◽  
Detection Experiment ◽  
Complex Molecules ◽  
The World ◽  
Life Detection ◽  
Molecular Complexity ◽  
The Universe

AbstractThe search for alien life is hard because we do not know what signatures are unique to life. We show why complex molecules found in high abundance are universal biosignatures and demonstrate the first intrinsic experimentally tractable measure of molecular complexity, called the molecular assembly index (MA). To do this we calculate the complexity of several million molecules and validate that their complexity can be experimentally determined by mass spectrometry. This approach allows us to identify molecular biosignatures from a set of diverse samples from around the world, outer space, and the laboratory, demonstrating it is possible to build a life detection experiment based on MA that could be deployed to extraterrestrial locations, and used as a complexity scale to quantify constraints needed to direct prebiotically plausible processes in the laboratory. Such an approach is vital for finding life elsewhere in the universe or creating de-novo life in the lab.

scholarly journals A hidden catalysis: metal-, and organocatalyst-free one-pot assembly of chiral aza-tricyclic molecules containing six contiguous stereocenters

2020 ◽  
Author(s):  
Dung Do
Keyword(s):  
Chemical Space ◽  
Structural Diversity ◽  
Therapeutic Agents ◽  
Chiral Molecules ◽  
One Pot ◽  
Complex Molecules ◽  
Chiral Complex ◽  
Enamine Catalysis ◽  
Daunting Challenge

<p></p><p>Chiral molecules with their defined 3-D structures are of paramount importance for the study of chemical biology and drug discovery. Having rich structural diversity and unique stereoisomerism, chiral molecules offer a large chemical space that can be explored for the design of new therapeutic agents.<sup>1</sup> In practice, chiral architectures are usually prepared from organometallic and organocatalytic processes where a transition metal or an organocatalyst is tailor-made for a desired reaction. As a result, developing a method that enables rapid assembly of chiral complex molecules under a metal- and organocatalyst-free condition represents a daunting challenge. Here we developed a straightforward one-pot procedure to create a chiral 3-D structure from 2-D structures and an amino acid without any chiral catalyst. The center of this research is the design of a <a>special chiral spiroimidazolidinone cyclohexadienone intermediate</a>, a merger of a chiral reactive substrate with multiple nucleophillic/electrophillic sites and a transient organocatalyst. <a>This unique substrate-catalyst (“sub-catalyst”) dual role of the intermediate was displayed in its aza-Michael/Michael cascade reaction with an </a>α,β-unsaturated aldehyde under an iminium/enamine catalysis. <a>The enhanced co-ordinational proximity of the chiral substrate and catalyst</a> in the transition state resulted in a substantial steric discrimination and an excellent overall diastereoselectivity. Aza-tricylic molecules with six contiguous stereocenters were assembled from <i>N</i>-alkylated aminophenols, α,β-unsaturated aldehydes and chiral α-amino acids under a hidden “sub-catalysis” where the strategically produced “sub-catalyst” does not present in initial components of the reaction. The success of this methodology will pave the way for many efficient preparations of chiral complex molecules.</p><br><p></p>

scholarly journals A hidden catalysis: metal-, and organocatalyst-free one-pot assembly of chiral aza-tricyclic molecules containing six contiguous stereocenters

2020 ◽  
Author(s):  
Dung Do
Keyword(s):  
Chemical Space ◽  
Structural Diversity ◽  
Therapeutic Agents ◽  
Chiral Molecules ◽  
One Pot ◽  
Complex Molecules ◽  
Chiral Complex ◽  
Enamine Catalysis ◽  
Daunting Challenge

<p></p><p>Chiral molecules with their defined 3-D structures are of paramount importance for the study of chemical biology and drug discovery. Having rich structural diversity and unique stereoisomerism, chiral molecules offer a large chemical space that can be explored for the design of new therapeutic agents.<sup>1</sup> In practice, chiral architectures are usually prepared from organometallic and organocatalytic processes where a transition metal or an organocatalyst is tailor-made for a desired reaction. As a result, developing a method that enables rapid assembly of chiral complex molecules under a metal- and organocatalyst-free condition represents a daunting challenge. Here we developed a straightforward one-pot procedure to create a chiral 3-D structure from 2-D structures and an amino acid without any chiral catalyst. The center of this research is the design of a <a>special chiral spiroimidazolidinone cyclohexadienone intermediate</a>, a merger of a chiral reactive substrate with multiple nucleophillic/electrophillic sites and a transient organocatalyst. <a>This unique substrate-catalyst (“sub-catalyst”) dual role of the intermediate was displayed in its aza-Michael/Michael cascade reaction with an </a>α,β-unsaturated aldehyde under an iminium/enamine catalysis. <a>The enhanced co-ordinational proximity of the chiral substrate and catalyst</a> in the transition state resulted in a substantial steric discrimination and an excellent overall diastereoselectivity. Aza-tricylic molecules with six contiguous stereocenters were assembled from <i>N</i>-alkylated aminophenols, α,β-unsaturated aldehydes and chiral α-amino acids under a hidden “sub-catalysis” where the strategically produced “sub-catalyst” does not present in initial components of the reaction. The success of this methodology will pave the way for many efficient preparations of chiral complex molecules.</p><br><p></p>

scholarly journals Ultrasound-accelerated arylthiomethylation of indole via multicomponent reaction in water catalyzed by acetic acid

2017 ◽  
Vol 1 (T1) ◽  
pp. 80-85
Author(s):  
Thi Thi Xuan Luu ◽  
Vinh Quang Pham
Keyword(s):  
Acetic Acid ◽  
Multicomponent Reactions ◽  
Main Product ◽  
Step Process ◽  
Magnetic Stirring ◽  
One Step ◽  
Molecular Complexity ◽  
Activation Conditions ◽  
Reaction In Water ◽  
Moderate Yield

Multicomponent reactions (MCRs) play an important role to create the molecular complexity in a one-step process. Based on the mechanism and process of Mannich-type reactions in the synthesis of Grammin, arylthiomethylation reactions of indole were performed by using three components: indole, p-thiocresol and a solution of formaldehyde (36%) under two activation conditions, e.g. magnetic stirring and ultrasonic irradiation. The main product, 3-(p-tolylthiomethyl)-1H-indole, was obtained in a moderate yield (54%) under short irradiation (40 minutes) by probe sonicator.

scholarly journals Bio-Catalysis in Multicomponent Reactions

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 5935
Author(s):  
Ndze Denis Jumbam ◽  
Wayiza Masamba
Keyword(s):  
Organic Chemistry ◽  
Combinatorial Chemistry ◽  
Enzyme Catalysis ◽  
Multicomponent Reactions ◽  
Research Area ◽  
Reaction Conditions ◽  
Complex Molecules ◽  
Diversity Oriented Synthesis ◽  
Active Research ◽  
Active Research Area

Enzyme catalysis is a very active research area in organic chemistry, because biocatalysts are compatible with and can be adjusted to many reaction conditions, as well as substrates. Their integration in multicomponent reactions (MCRs) allows for simple protocols to be implemented in the diversity-oriented synthesis of complex molecules in chemo-, regio-, stereoselective or even specific modes without the need for the protection/deprotection of functional groups. The application of bio-catalysis in MCRs is therefore a welcome and logical development and is emerging as a unique tool in drug development and discovery, as well as in combinatorial chemistry and related areas of research.

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