scholarly journals Structural Contributions to Autocatalysis and Asymmetric Amplification in the Soai Reaction

2020 ◽  
Author(s):  
Soumitra Athavale ◽  
Adam Simon ◽  
Kendall N Houk ◽  
Scott Denmark
Keyword(s):  
Organic Chemistry ◽  
Substrate Binding ◽  
New Paradigm ◽  
Unique Position ◽  
Structure Activity ◽  
Alkyl Groups ◽  
Mixed Catalyst ◽  
Substrate Reactivity ◽  
Asymmetric Autocatalysis ◽  
Soai Reaction

Diisopropylzinc alkylation of pyrimidine aldehydes – the Soai reaction, with its astonishing attribute of amplifying asymmetric autocatalysis, occupies a unique position in organic chemistry and stands as an eminent challenge for mechanistic elucidation. A new paradigm of ‘mixed catalyst substrate’ experiments with pyrimidine and pyridine systems allows a disconnection of catalysis from autocatalysis, providing insights into the role played by reactant and alkoxide structure. The alkynyl substituent favorably tunes catalyst solubility, aggregation and conformation while modulating substrate reactivity and selectivity. The alkyl groups and the heteroaromatic core play further complementary roles in catalyst aggregation and substrate binding. In the study of these structure activity relationships, novel pyridine substrates demonstrating amplifying autocatalysis were identified. Comparison of three autocatalytic systems representing a continuum of nitrogen Lewis basicity strength suggests how the strength of N-Zn binding events is a predominant contributor towards the rate of autocatalytic progression.<br><div> </div>

scholarly journals Structural Contributions to Autocatalysis and Asymmetric Amplification in the Soai Reaction

2020 ◽  
Author(s):  
Soumitra Athavale ◽  
Adam Simon ◽  
Kendall N Houk ◽  
Scott Denmark
Keyword(s):  
Organic Chemistry ◽  
Substrate Binding ◽  
New Paradigm ◽  
Unique Position ◽  
Structure Activity ◽  
Alkyl Groups ◽  
Mixed Catalyst ◽  
Substrate Reactivity ◽  
Asymmetric Autocatalysis ◽  
Soai Reaction

Diisopropylzinc alkylation of pyrimidine aldehydes – the Soai reaction, with its astonishing attribute of amplifying asymmetric autocatalysis, occupies a unique position in organic chemistry and stands as an eminent challenge for mechanistic elucidation. A new paradigm of ‘mixed catalyst substrate’ experiments with pyrimidine and pyridine systems allows a disconnection of catalysis from autocatalysis, providing insights into the role played by reactant and alkoxide structure. The alkynyl substituent favorably tunes catalyst solubility, aggregation and conformation while modulating substrate reactivity and selectivity. The alkyl groups and the heteroaromatic core play further complementary roles in catalyst aggregation and substrate binding. In the study of these structure activity relationships, novel pyridine substrates demonstrating amplifying autocatalysis were identified. Comparison of three autocatalytic systems representing a continuum of nitrogen Lewis basicity strength suggests how the strength of N-Zn binding events is a predominant contributor towards the rate of autocatalytic progression.<br><div> </div>

Carbohydrazide analogues: a review of synthesis and biological activities

2021 ◽  
Vol 21 ◽  
Author(s):  
Ebuka Leonard Onyeyilim ◽  
Mercy Amarachi Ezeokonkwo ◽  
David Izuchukwu Ugwu ◽  
Chiamaka Peace Uzoewulu ◽  
Florence Uchenna Eze ◽  
...  
Keyword(s):  
Organic Chemistry ◽  
Inorganic Chemistry ◽  
Schiff Bases ◽  
Bioactive Compounds ◽  
Biological Activities ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Important Class ◽  
Synthetic Route ◽  
Structure Activity

: Carbohydrazides and their Schiff bases are important class of heterocycles that are not only employed in the area of organic chemistry, but also have tremendous applications in physical and inorganic chemistry. A series of potential bioactive compounds, containing carbohydrazide functionality and their hydrazone derivatives have been synthesized and screened for antibacterial, anticancer, antifungal and anti-inflammatory etc. This brief review discloses some synthetic route to so many reported carbohydrazides, their Schiff bases, their biological activities and their structure activity relationship.

scholarly journals Shifting the Education Paradigm: Why International Borrowing is No Longer Sufficient for Improving Education in China

2018 ◽  
Vol 1 (1) ◽  
pp. 76-106 ◽  
Author(s):  
Yong Zhao
Keyword(s):  
Educational Policies ◽  
Chinese Education ◽  
Assessment Data ◽  
New Paradigm ◽  
The West ◽  
Unique Position ◽  
The World ◽  
International Assessment ◽  
International Borrowing ◽  
Education In China

Purpose —The purpose of this article is to examine the consequences of mutual borrowing of educational policies and practices between the East and the West and implications for Chinese education. Design/Approach/Methods —This paper draws upon a wide variety of historical, cultural, and international assessment data. Findings —The analyses found that the mutual borrowing is unlikely to improve education to the extent that the future world demands. Originality/Value —Thus, the article concludes that instead of wasting resources and time on learning from each other's past, education systems around the world should work on inventing a new paradigm of education. China is in a unique position to work on the new paradigm.

scholarly journals Synergistic Lethality of a Binary Inhibitor ofMycobacterium tuberculosisKasA

mBio ◽  
2018 ◽  
Vol 9 (6) ◽  
Author(s):  
Pradeep Kumar ◽  
Glenn C. Capodagli ◽  
Divya Awasthi ◽  
Riju Shrestha ◽  
Karishma Maharaja ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Cell Wall ◽  
Mycobacterium Tuberculosis ◽  
Substrate Binding ◽  
Content Type ◽  
X Ray ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Transcriptional Pattern

ABSTRACTWe report GSK3011724A (DG167) as a binary inhibitor of β-ketoacyl-ACP synthase (KasA) inMycobacterium tuberculosis. Genetic and biochemical studies established KasA as the primary target. The X-ray crystal structure of the KasA-DG167 complex refined to 2.0-Å resolution revealed two interacting DG167 molecules occupying nonidentical sites in the substrate-binding channel of KasA. The binding affinities of KasA to DG167 and its analog, 5g, which binds only once in the substrate-binding channel, were determined, along with the KasA-5g X-ray crystal structure. DG167 strongly augmented thein vitroactivity of isoniazid (INH), leading to synergistic lethality, and also synergized in an acute mouse model ofM. tuberculosisinfection. Synergistic lethality correlated with a unique transcriptional signature, including upregulation of oxidoreductases and downregulation of molecular chaperones. The lead structure-activity relationships (SAR), pharmacokinetic profile, and detailed interactions with the KasA protein that we describe may be applied to evolve a next-generation therapeutic strategy for tuberculosis (TB).IMPORTANCECell wall biosynthesis inhibitors have proven highly effective for treating tuberculosis (TB). We discovered and validated members of the indazole sulfonamide class of small molecules as inhibitors ofMycobacterium tuberculosisKasA—a key component for biosynthesis of the mycolic acid layer of the bacterium’s cell wall and the same pathway as that inhibited by the first-line antitubercular drug isoniazid (INH). One lead compound, DG167, demonstrated synergistic lethality in combination with INH and a transcriptional pattern consistent with bactericidality and loss of persisters. Our results also detail a novel dual-binding mechanism for this compound as well as substantial structure-activity relationships (SAR) that may help in lead optimization activities. Together, these results suggest that KasA inhibition, specifically, that shown by the DG167 series, may be developed into a potent therapy that can synergize with existing antituberculars.

Quantitative Structure-Activity Relationships (QSARs) for Materials Science

2001 ◽  
Vol 700 ◽  
Author(s):  
Krishna Rajan ◽  
Changwon Suh ◽  
Arun Rajagopalan ◽  
Xiang Li
Keyword(s):  
Organic Chemistry ◽  
Materials Science ◽  
Molecular Level ◽  
Combinatorial Synthesis ◽  
Quantitative Structure ◽  
New Materials ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Computational Aspects ◽  
Quantitative Structure Activity Relationships

AbstractThe field of combinatorial synthesis and “artificial intelligence” in materials science is still in its infancy. In order to develop and accelerated strategy in the discovery of new materials and processes, requires the need to integrate both the experimental aspects of combinatorial synthesis with the computational aspects of information based design of materials. In biology and organic chemistry, this has been accomplished by developing descriptors which help to specify “quantitative structure- activity relationships” at the molecular level. If materials science is to adopt these strategies as well, a similar framework of “QSARs” is required. In this paper, we outline some approaches that can lay the foundations for QSARs in materials science.

Sign in / Sign up

Export Citation Format

Share Document