MCDCalc: Markov Chain Molecular Descriptors Calculator for Medicinal Chemistry

Aim: Cheminformatics models are able to predict different outputs (activity, property, chemical reactivity) in single molecules or complex molecular systems (catalyzed organic synthesis, metabolic reactions, nanoparticles, etc.). Background: Cheminformatics models are able to predict different outputs (activity, property, chemical reactivity) in single molecules or complex molecular systems (catalyzed organic synthesis, metabolic reactions, nanoparticles, etc.). Objective: Cheminformatics prediction of complex catalytic enantioselective reactions is a major goal in organic synthesis research and chemical industry. Markov Chain Molecular Descriptors (MCDs) have been largely used to solve Cheminformatics problems. There are different types of Markov chain descriptors such as Markov-Shannon entropies (Shk), Markov Means (Mk), Markov Moments (πk), etc. However, there are other possible MCDs that have not been used before. In addition, the calculation of MCDs is done very often using specific software not always available for general users and there is not an R library public available for the calculation of MCDs. This fact, limits the availability of MCMDbased Cheminformatics procedures. Methods: We studied the enantiomeric excess ee(%)[Rcat] for 324 α-amidoalkylation reactions. These reactions have a complex mechanism depending on various factors. The model includes MCDs of the substrate, solvent, chiral catalyst, product along with values of time of reaction, temperature, load of catalyst, etc. We tested several Machine Learning regression algorithms. The Random Forest regression model has R2 > 0.90 in training and test. Secondly, the biological activity of 5644 compounds against colorectal cancer was studied. Results: We developed very interesting model able to predict with Specificity and Sensitivity 70-82% the cases of preclinical assays in both training and validation series. Conclusion: The work shows the potential of the new tool for computational studies in organic and medicinal chemistry.

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Cascade CuH-Catalyzed Conversion of Alkynes to Enantioenriched 1,1-Disubstituted Products

10.26434/chemrxiv.7961633.v1 ◽

2019 ◽

Author(s):

De-Wei Gao ◽

Yang Gao ◽

Huiling Shao ◽

Tian-Zhang Qiao ◽

Xin Wang ◽

...

Keyword(s):

Organic Synthesis ◽

Medicinal Chemistry ◽

Proteasome Inhibitors ◽

Building Blocks ◽

Unique Role ◽

Efficient Strategy ◽

Carbon Centers ◽

Rapid Access ◽

Cascade Catalysis ◽

Privileged Scaffolds

Enantioenriched α-aminoboronic acids play a unique role in medicinal chemistry and have emerged as privileged pharmacophores in proteasome inhibitors. Additionally, they represent synthetically useful chiral building blocks in organic synthesis. Recently, CuH-catalyzed asymmetric alkene hydrofunctionalization has become a powerful tool to construct stereogenic carbon centers. In contrast, applying CuH cascade catalysis to achieve reductive 1,1-difunctionalization of alkynes remains an important, but largely unaddressed, synthetic challenge. Herein, we report an efficient strategy to synthesize α-aminoboronates via CuH-catalyzed hydroboration/hydroamination cascade of readily available alkynes. Notably, this transformation selectively delivers the desired 1,1-heterodifunctionalized product in favor of alternative homodifunctionalized, 1,2-heterodifunctionalized, or reductively monofunctionalized byproducts, thereby offering rapid access to these privileged scaffolds with high chemo-, regio- and enantioselectivity.

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Catalytic, Enantioselective Syn-Diamination of Alkenes

10.26434/chemrxiv.9894416 ◽

2019 ◽

Author(s):

Zhonglin Tao ◽

Brad Gilbert ◽

Scott Denmark

Keyword(s):

General Solution ◽

Organic Synthesis ◽

Medicinal Chemistry ◽

Catalytic Cycle ◽

Bifunctional Nucleophile

The enantioselective, vicinal diamination of alkenes represents one of the stereocontrolled additions that remains an outstanding challenge in organic synthesis. A general solution to this problem would enable the efficient and selective preparation of widely useful, enantioenriched diamines for applications in medicinal chemistry and catalysis. In this Article we describe the first enantioselective, syn-diamination of simple alkenes mediated by a chiral, enantioenriched organoselenium catalyst together with a N,N’-bistosyl urea as the bifunctional nucleophile and N-fluorocollidinium tetrafluoroborate as the stoichiometric oxidant. Diaryl, aryl-alkyl, and alkyl-alkyl olefins bearing a variety of substituents are all diaminated in consistently high enantioselectivities selectivities but variable yields. The reaction likely proceeds through a Se(II)/Se(IV) redox catalytic cycle reminiscent of the syn-dichlorination reported previously. Furthermore, the syn-stereospecificity of the transformation shows promise for highly enantioselective diaminations of alkenes with no strong steric or electronic bias.

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General Theory for Multiple Input-Output Perturbations in Complex Molecular Systems. 1. Linear QSPR Electronegativity Models in Physical, Organic, and Medicinal Chemistry

Current Topics in Medicinal Chemistry ◽

10.2174/1568026611313140011 ◽

2013 ◽

Vol 13 (14) ◽

pp. 1713-1741 ◽

Cited By ~ 63

Author(s):

Humberto Gonzalez-Diaz ◽

Sonia Arrasate ◽

Asier Gomez-SanJuan ◽

Nuria Sotomayor ◽

Esther Lete ◽

...

Keyword(s):

General Theory ◽

Medicinal Chemistry ◽

Input Output ◽

Molecular Systems ◽

Physical Organic ◽

Multiple Input

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ChemInform Abstract: Organic Synthesis and Medicinal Chemistry

ChemInform ◽

10.1002/chin.200102294 ◽

2001 ◽

Vol 32 (2) ◽

pp. no-no

Author(s):

Fulvio Gualtieri

Keyword(s):

Organic Synthesis ◽

Medicinal Chemistry

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Enzymes in organic synthesis. 33. Stereoselective pig liver esterase-catalyzed hydrolyses of meso cyclopentyl-, tetrahydrofuranyl-, and tetrahydrothiophenyl-1,3-diesters

Canadian Journal of Chemistry ◽

10.1139/v85-074 ◽

1985 ◽

Vol 63 (2) ◽

pp. 452-456 ◽

Cited By ~ 29

Author(s):

J. Bryan Jones ◽

R. Scott Hinks ◽

Philip G. Hultin

Keyword(s):

Organic Synthesis ◽

Absolute Configuration ◽

Enantiomeric Excess ◽

Membered Ring ◽

Pig Liver ◽

Pig Liver Esterase ◽

Preparative Scale ◽

Liver Esterase ◽

The Absolute ◽

Enzymes In Organic Synthesis

Preparative-scale pig liver esterase-catalyzed hydrolyses of five-membered ring meso-1,3-diesters are enantiotopically selective. While pro-S enantiotopic selectivity is exhibited in each case, the absolute configuration sense of the hydrolysis in the cyclopentyl series is opposite to that of both the tetrahydrofuranyl and tetrahydrothiophenyl diesters. The enantiomeric excess levels induced are in the 34–46% range.

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Study of the Stability and Chemical Reactivity of a Series of Tetrazole Pyrimidine Hybrids by the Density Functional Theory Method (DFT)

Oriental Journal Of Chemistry ◽

10.13005/ojc/370406 ◽

2021 ◽

Vol 37 (4) ◽

pp. 805-812

Author(s):

Ahissandonatien Ehouman ◽

Adjoumanirodrigue Kouakou ◽

Fatogoma Diarrassouba ◽

Hakim Abdel Aziz Ouattara ◽

Paulin Marius Niamien

Keyword(s):

Density Functional ◽

Theoretical Study ◽

Molecular Descriptors ◽

Chemical Reactivity ◽

Density Functional Theory Method ◽

Functional Theory ◽

Reactivity Descriptors ◽

The Density Functional Theory ◽

The Stability ◽

Global Reactivity Descriptors

Our theoretical study of stability and reactivity was carried out on six (06) molecules of a series of pyrimidine tetrazole hybrids (PTH) substituted with H, F, Cl, Br, OCH3 and CH3 atoms and groups of atoms using the density function theory (DFT). Analysis of the thermodynamic formation quantities confirmed the formation and existence of the series of molecules studied. Quantum chemical calculations at the B3LYP / 6-311G (d, p) level of theory determined molecular descriptors. Global reactivity descriptors were also determined and analyzed. Thus, the results showed that the compound PTH_1 is the most stable, and PTH_5 is the most reactive and nucleophilic. Similarly, the compound PTH_4 is the most electrophilic. The analysis of the local descriptors and the boundary molecular orbitals allowed us to identify the preferred atoms for electrophilic and nucleophilic attacks.

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Construction of N-heterocycles via Pd-mediated C–H activation/annulation strategies

Organic & Biomolecular Chemistry ◽

10.1039/d1ob02146j ◽

2022 ◽

Author(s):

Mengyu Qiu ◽

Xuegang Fu ◽

Peng Fu ◽

Jianhui Huang

Keyword(s):

Natural Products ◽

Organic Synthesis ◽

Material Science ◽

Medicinal Chemistry ◽

Drug Molecules

N-heterocycles can be found in natural products and drug molecules, which are indispensable components in the area of organic synthesis, medicinal chemistry and material science. The construction of these N-containing...

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Metalloporphyrin catalysts for organic synthesis

Journal of Porphyrins and Phthalocyanines ◽

10.1142/s1088424604000507 ◽

2004 ◽

Vol 08 (09) ◽

pp. 1166-1171 ◽

Cited By ~ 31

Author(s):

Gérard Simonneaux ◽

Pietro Tagliatesta

Keyword(s):

Organic Synthesis ◽

Enantiomeric Excess ◽

Catalytic Reactions ◽

Terminal Alkynes ◽

Asymmetric Oxidation ◽

Carbene Transfer ◽

Catalytic Asymmetric ◽

Chiral Systems ◽

Metalloporphyrin Catalysts

Novel chiral systems for the catalytic asymmetric oxidation and cyclopropanation of olefins based on metalloporphyrins containing iron, ruthenium and manganese, have been recently introduced. High catalyst turnover numbers and sometimes high enantiomeric excess were observed. New catalytic reactions with metalloporphyrins have recently been reported; these are the olefination of aldehydes and cyclotrimerization of terminal alkynes. Dendrimers and polymers containing metalloporphyrins, have also been found to be efficient catalysts for oxidation and carbene transfer.

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