General Cyclopropane Assembly via Enantioselective Redox-Active Carbene Transfer to Aliphatic Olefins

2018 ◽  
Author(s):  
Marc Montesinos-Magraner ◽  
Matteo Costantini ◽  
Rodrigo Ramirez-Contreras ◽  
Michael E. Muratore ◽  
Magnus J. Johansson ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Asymmetric Synthesis ◽  
Chemical Space ◽  
Synthetic Approach ◽  
Asymmetric Cyclopropanation ◽  
Redox Active ◽  
Wide Range ◽  
Leaving Group ◽  
Stereoelectronic Properties ◽  
Carbene Transfer

Asymmetric cyclopropane synthesis currently requires bespoke strategies, methods, substrates and reagents, even when targeting similar compounds. This limits the speed and chemical space available for discovery campaigns. Here we introduce a practical and versatile diazocompound, and we demonstrate its performance in the first unified asymmetric synthesis of functionalized cyclopropanes. We found that the redox-active leaving group in this reagent enhances the reactivity and selectivity of geminal carbene transfer. This effect enabled the asymmetric cyclopropanation of a wide range of olefins including unactivated aliphatic alkenes, enabling the 3-step total synthesis of (–)-dictyopterene A. This unified synthetic approach delivers high enantioselectivities that are independent of the stereoelectronic properties of the functional groups transferred. Our results demonstrate that orthogonally-differentiated diazocompounds are viable and advantageous equivalents of single-carbon chirons<i>.</i>

General Cyclopropane Assembly via Enantioselective Redox-Active Carbene Transfer to Aliphatic Olefins

2018 ◽  
Author(s):  
Marc Montesinos-Magraner ◽  
Matteo Costantini ◽  
Rodrigo Ramirez-Contreras ◽  
Michael E. Muratore ◽  
Magnus J. Johansson ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Asymmetric Synthesis ◽  
Chemical Space ◽  
Synthetic Approach ◽  
Asymmetric Cyclopropanation ◽  
Redox Active ◽  
Wide Range ◽  
Leaving Group ◽  
Stereoelectronic Properties ◽  
Carbene Transfer

Asymmetric cyclopropane synthesis currently requires bespoke strategies, methods, substrates and reagents, even when targeting similar compounds. This limits the speed and chemical space available for discovery campaigns. Here we introduce a practical and versatile diazocompound, and we demonstrate its performance in the first unified asymmetric synthesis of functionalized cyclopropanes. We found that the redox-active leaving group in this reagent enhances the reactivity and selectivity of geminal carbene transfer. This effect enabled the asymmetric cyclopropanation of a wide range of olefins including unactivated aliphatic alkenes, enabling the 3-step total synthesis of (–)-dictyopterene A. This unified synthetic approach delivers high enantioselectivities that are independent of the stereoelectronic properties of the functional groups transferred. Our results demonstrate that orthogonally-differentiated diazocompounds are viable and advantageous equivalents of single-carbon chirons<i>.</i>

Total Synthesis of Axially-Chiral Cannabinols: A New Platform for Cannabinoid-Based Drug Discovery

2019 ◽  
Author(s):  
Primali Navaratne ◽  
Jenny Wilkerson ◽  
Kavindri Ranasinghe ◽  
Evgeniya Semenova ◽  
Lance McMahon ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Total Synthesis ◽  
Ground State ◽  
Chemical Space ◽  
Modern Medicine ◽  
The Novel ◽  
Pharmaceutical Development ◽  
Bioactive Component ◽  
Axially Chiral ◽  
New Directions

<div> <div> <div> <p>Phytocannabinoids, molecules isolated from cannabis, are gaining attention as promising leads in modern medicine, including pain management. Considering the urgent need for combating the opioid crisis, new directions for the design of cannabinoid-inspired analgesics are of immediate interest. In this regard, we have hypothesized that axially-chiral-cannabinols (ax-CBNs), unnatural (and unknown) isomers of cannabinol (CBN) may be valuable scaffolds for cannabinoid-inspired drug discovery. There are multiple reasons for thinking this: (a) ax-CBNs would have ground-state three-dimensionality akin to THC, a key bioactive component of cannabis, (b) ax-CBNs at their core structure are biaryl molecules, generally attractive platforms for pharmaceutical development due to their ease of functionalization and stability, and (c) atropisomerism with respect to phytocannabinoids is unexplored “chemical space.” Herein we report a scalable total synthesis of ax-CBNs, examine physical properties experimentally and computationally, and provide preliminary behavioral and analgesic analysis of the novel scaffolds. </p> </div> </div> </div>

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.

Regioselective Functionalization of N-Fused Heteroaromatics via FeCl3-Catalyzed Nucleophilic Addition to Activated N-Heterocycles

Synthesis ◽  
2020 ◽  
Author(s):  
Ikyon Kim ◽  
Sung June Kim ◽  
Sunhee Lee
Keyword(s):  
Aromatic Compounds ◽  
Nucleophilic Addition ◽  
Chemical Space ◽  
Wide Range ◽  
Regioselective Functionalization

AbstractBroadening of nitrogen-fused heteroaromatic chemical space such as indolizine and pyrrolo[1,2-a]pyrazine was achieved via FeCl­3-catalyzed nucleophilic addition of these N-fused aromatic compounds to a wide range of azolinium systems generated in situ, leading to novel N-fused heteroaromatic scaffolds with dearomatized N-heterocyclic substituents regioselectively. Nucleophilic addition of indolizines and pyrrolo[1,2-a]pyrazines mainly occurred at the C1 position of the isoquinoliniums and at the C4 site of the quinoliniums.

Historical Dynamics

2018 ◽  
Author(s):  
Peter Turchin
Keyword(s):  
Religious Conversion ◽  
Synthetic Approach ◽  
Dynamical Processes ◽  
Factors Affecting ◽  
Historical Processes ◽  
Wide Range ◽  
Historical Dynamics ◽  
State Breakdown ◽  
Political Economic ◽  
High Degree

Many historical processes are dynamic. Populations grow and decline. Empires expand and collapse. Religions spread and wither. Natural scientists have made great strides in understanding dynamical processes in the physical and biological worlds using a synthetic approach that combines mathematical modeling with statistical analyses. Taking up the problem of territorial dynamics—why some polities at certain times expand and at other times contract—this book shows that a similar research program can advance our understanding of dynamical processes in history. The book develops hypotheses from a wide range of social, political, economic, and demographic factors: geopolitics, factors affecting collective solidarity, dynamics of ethnic assimilation/religious conversion, and the interaction between population dynamics and sociopolitical stability. It then translates these into a spectrum of mathematical models, investigates the dynamics predicted by the models, and contrasts model predictions with empirical patterns. The book's highly instructive empirical tests demonstrate that certain models predict empirical patterns with a very high degree of accuracy. For instance, one model accounts for the recurrent waves of state breakdown in medieval and early modern Europe. And historical data confirm that ethno-nationalist solidarity produces an aggressively expansive state under certain conditions (such as in locations where imperial frontiers coincide with religious divides). The strength of the book's results suggests that the synthetic approach advocated can significantly improve our understanding of historical dynamics.

Alkene Difunctionalization Directed by Free Amines: Diamine Synthesis via Nickel-Catalyzed 1,2-Carboamination

2021 ◽  
Author(s):  
Taeho Kang ◽  
José Manuel González ◽  
Zi-Qi Li ◽  
Klement Foo ◽  
Peter Cheng ◽  
...  
Keyword(s):  
Nickel Catalyst ◽  
Room Temperature ◽  
Kinetic Studies ◽  
Fine Tuning ◽  
Secondary Amines ◽  
Protecting Group ◽  
Wide Range ◽  
Leaving Group ◽  
Primary And Secondary Amines ◽  
Reaction Proceeds

A versatile method to access differentially substituted 1,3- and 1,4-diamines via a nickel-catalyzed three-component 1,2-carboamination of alkenyl amines with aryl/alkenylboronic ester nucleophiles and N–O electrophiles is reported. The reaction proceeds efficiently with free primary and secondary amines without needing a directing auxiliary or protecting group, and is enabled by fine-tuning the leaving group on the N–O reagent. The transformation is highly regioselective and compatible with a wide range of coupling partners and alkenyl amine substrates, all performed at room temperature. A series of kinetic studies support a mechanism in which alkene coordination to the nickel catalyst is turnover-limiting.

scholarly journals Non-Stoichiometric Redox Active Perovskite Materials for Solar Thermochemical Fuel Production: A Review

Catalysts ◽  
2018 ◽  
Vol 8 (12) ◽  
pp. 611 ◽  
Author(s):  
Anita Haeussler ◽  
Stéphane Abanades ◽  
Julien Jouannaux ◽  
Anne Julbe
Keyword(s):  
Carbon Dioxide ◽  
Solar Energy ◽  
Energy Conversion ◽  
Operating Conditions ◽  
Solar Fuel ◽  
Fuel Production ◽  
Concentrated Solar Energy ◽  
Redox Active ◽  
Conversion Rates ◽  
Wide Range

Due to the requirement to develop carbon-free energy, solar energy conversion into chemical energy carriers is a promising solution. Thermochemical fuel production cycles are particularly interesting because they can convert carbon dioxide or water into CO or H2 with concentrated solar energy as a high-temperature process heat source. This process further valorizes and upgrades carbon dioxide into valuable and storable fuels. Development of redox active catalysts is the key challenge for the success of thermochemical cycles for solar-driven H2O and CO2 splitting. Ultimately, the achievement of economically viable solar fuel production relies on increasing the attainable solar-to-fuel energy conversion efficiency. This necessitates the discovery of novel redox-active and thermally-stable materials able to split H2O and CO2 with both high-fuel productivities and chemical conversion rates. Perovskites have recently emerged as promising reactive materials for this application as they feature high non-stoichiometric oxygen exchange capacities and diffusion rates while maintaining their crystallographic structure during cycling over a wide range of operating conditions and reduction extents. This paper provides an overview of the best performing perovskite formulations considered in recent studies, with special focus on their non-stoichiometry extent, their ability to produce solar fuel with high yield and performance stability, and the different methods developed to study the reaction kinetics.

scholarly journals Oxazolidinones as Chiral Auxiliaries in the Asymmetric 1,4-Conjugate Addition Reaction Applied to the Total Synthesis of Natural Products: A Supplemental Mini-Review

2018 ◽  
Vol 15 (1) ◽  
pp. 3-20 ◽  
Author(s):  
Vahideh Zadsirjan ◽  
Majid M. Heravi
Keyword(s):  
Total Synthesis ◽  
Biological Activities ◽  
Conjugate Addition ◽  
Chiral Auxiliary ◽  
Addition Reactions ◽  
Chiral Auxiliaries ◽  
Complex Molecules ◽  
Total Syntheses ◽  
Naturally Occurring ◽  
Wide Range

Background: The most frequently used chiral auxiliaries, oxazolidinones (Evans' oxazolidinones) have been employed in 1,4-congugate addition reactions to α,β-unsaturated carbonyl compounds. Supplementary to our previous reports in this mini-review, we attempted to underscore the applications of this strategy in a step (steps) in the total synthesis of some naturally occurring compounds exhibiting diverse biological activities. Objective: In this mini-review, we try to underscore the applications of oxazolidinones (Evans’ oxazolidinones) in 1,4-congugate addition reactions to α,β-unsaturated carbonyl in the total synthesis of some naturally occurring compounds exhibiting diverse biological activities. Conclusion: In spite of well-known superiority of asymmetric catalyzed reactions, the use of auxiliarycontrolled reactions are still considered as commanding, vital and sometimes as only tools in the generation of stereogenic centers during the construction of complex molecules and total synthesis of naturally occurring compounds. The commercial availability, or readily accessibility of a wide variety of chiral amino alcohols as starting materials to synthesize a wide range of oxazolidinones is the merits of them. In addition, the ease of removal and subjection to various and diverse stereoselective reactions make oxazolidinones as the ideal and superior chiral auxiliaries. In this regard, they were successfully used in asymmetric 1,4-conjugate addition reactions with high stereoselectivities. The high degree of asymmetric induction can be attributed to the rigid chelation of N-acyloxazolidinones with metal ions, as well as the covering of one face of the system by the bulkiness of 4-substituent. In summary, in this report, the importance of the applications of chiral oxazolidinones as suitable chiral auxiliaries in the stereoselective, 1,4-conjugate addition reactions in asymmetric synthesis and in particular, the total synthesis of naturally occurring compounds and some complex molecules were underscored. Noticeably, in these total syntheses, this chiral auxiliary is controlling the stereochemistry of a newly created stereogenic center as well as preserving the configuration of other chiral centers, which already have been presented in the precursor. General methods have been established for the attachment of the chiral auxiliary as a moiety to the substrate molecule in high to excellent yields. At the end of these reactions, this auxiliary can be easily removed leaving various desired reactive motifs for the next step in multi-step synthesis.

scholarly journals Heronapyrrole D: A case of co-inspiration of natural product biosynthesis, total synthesis and biodiscovery

2014 ◽  
Vol 10 ◽  
pp. 1228-1232 ◽  
Author(s):  
Jens Schmidt ◽  
Zeinab Khalil ◽  
Robert J Capon ◽  
Christian B W Stark
Keyword(s):  
Antibacterial Activity ◽  
Natural Products ◽  
Total Synthesis ◽  
Asymmetric Synthesis ◽  
Natural Product ◽  
Joint Effort ◽  
Natural Product Biosynthesis ◽  
New Members ◽  
Degree Of Oxidation ◽  
Rare Class

The heronapyrroles A–C have first been isolated from a marine-derived Streptomyces sp. (CMB-0423) in 2010. Structurally, these natural products feature an unusual nitropyrrole system to which a partially oxidized farnesyl chain is attached. The varying degree of oxidation of the sesquiterpenyl subunit in heronapyrroles A–C provoked the hypothesis that there might exist other hitherto unidentified metabolites. On biosynthetic grounds a mono-tetrahydrofuran-diol named heronapyrrole D appeared a possible candidate. We here describe a short asymmetric synthesis of heronapyrrole D, its detection in cultivations of CMB-0423 and finally the evaluation of its antibacterial activity. We thus demonstrate that biosynthetic considerations and the joint effort of synthetic and natural product chemists can result in the identification of new members of a rare class of natural products.

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