Depsidone synthesis. XII. Some exploratory synthetic routes to highly functionalized depsidones

1978 ◽  
Vol 31 (6) ◽  
pp. 1383 ◽  
Author(s):  
T Sala ◽  
MV Sargent

Attempts to synthesize the depsidones virensic acid (1), physciosporin (2), and pannarin (3) by routes based on the Ullmann ether condensation and the Hems reaction are described. Selective functionalization of highly substituted p-xylenes by photobromination is reported.

2022 ◽  
Author(s):  
Sebastian Gergel ◽  
Jordi Soler ◽  
Alina Klein ◽  
Kai Schülke ◽  
Bernhard Hauer ◽  
...  

The direct regioselective oxidation of internal alkenes to ketones could simplify synthetic routes and solve a longstanding challenge in synthesis. This reaction is of particular importance because ketones are predominant moieties in valuable products as well as crucial intermediates in synthesis. Here we report the directed evolution of a ketone synthase that oxidizes internal alkenes directly to ketones with several thousand turnovers. The evolved ketone synthase benefits from more than a dozen crucial mutations, most of them distal to the active site. Computational analysis reveals that all these mutations collaborate to facilitate the formation of a highly reactive carbocation intermediate by generating a confined, rigid and preorganized active site through an enhanced dynamical network. The evolved ketone synthase fully exploits a catalytic cycle that has largely eluded small molecule catalysis and consequently enables various challenging functionalization reactions of internal alkenes. This includes the first catalytic, enantioselective oxidation of internal alkenes to ketones, as well as the formal asymmetric hydration and hydroamination of unactivated internal alkenes in combination with other biocatalysts.


2010 ◽  
Vol 38 (1) ◽  
pp. 80-98 ◽  
Author(s):  
M. Gerster ◽  
C. Fagouri ◽  
E. Peregi

Abstract One challenge facing green tire technology is to achieve good silica hydrophobation/dispersion within the polymer matrix without a detrimental increase in the rubber compound’s viscosity during compounding. This phenomenon is well known to be induced by premature and unwanted coupling and/or crosslinking of the traditional coupling agents. The current state-of-the-art polysulfides silanes, bis(3-triethoxysilylpropyl)tetrasulfide and to a lesser extent bis(3-triethoxysilylpropyl)disulfide (“Product Application—VP Si 75/VP X 75-S in the Rubber Industry,” Degussa Hüls Report No. PA 723.1E), need to be carefully incorporated with careful temperature control during the rubber compounding to prevent this “scorchy” behavior. This paper will present novel monofunctional silanes which are suited for preparing highly silica-loaded rubber compounds of superior processability, while applying fewer mixing passes, thereby reducing mixing times which can lead to improved productivity and cost savings. Additionally, these safer coupling agents can be processed at higher temperatures which can, again, lead to reduced mixing time and better ethanol removal thereby improving the tire’s physical properties and reducing the volatile organic compounds generated during the tire’s use. The rubber compounds produced using these monofunctional silanes are characterized by lower Mooney viscosity and improved processability. Advantageously, within these novel chemical classes of coupling agents, selective functionalization of the silanes allows production of tailor-made coupling agents which can respond to the specific requirements of the tire industry (Vilgis, T. A. and Heinrich, G., “Die Physic des Autoreifens,” Physikalische Blätter, Vol. 57, 2001, pp. 1–7).


2019 ◽  
Author(s):  
Sandeep Pimparkar ◽  
Trisha Bhattacharya ◽  
Arun Maji ◽  
Argha Saha ◽  
Ramasamy Jayarajan ◽  
...  

The significance of site selective functionalization stands upon the superior selectivity, easy synthesis and diverse product utility. In this work we demonstrate the <i>para</i>-selective introduction of versatile nitrile moiety, enabled by detachable and reusable H-bonded auxiliary. The methodology holds its efficiency irrespective of substrate electronic bias. The conspicuous shift in the step energetics was probed by both experimental and computational mechanistic tools heralds the inception of <i>para</i>-deuteration. The synthetic impact of the methodology was highlighted with reusability of directing group and post synthetic modifications


2019 ◽  
Author(s):  
Sandeep Pimparkar ◽  
Trisha Bhattacharya ◽  
Arun Maji ◽  
Argha Saha ◽  
Ramasamy Jayarajan ◽  
...  

The significance of site selective functionalization stands upon the superior selectivity, easy synthesis and diverse product utility. In this work we demonstrate the <i>para</i>-selective introduction of versatile nitrile moiety, enabled by detachable and reusable H-bonded auxiliary. The methodology holds its efficiency irrespective of substrate electronic bias. The conspicuous shift in the step energetics was probed by both experimental and computational mechanistic tools heralds the inception of <i>para</i>-deuteration. The synthetic impact of the methodology was highlighted with reusability of directing group and post synthetic modifications


2020 ◽  
Author(s):  
Tsuyoshi Mita ◽  
Yu Harabuchi ◽  
Satoshi Maeda

The systematic exploration of synthetic pathways to afford a desired product through quantum chemical calculations remains a considerable challenge. In 2013, Maeda et al. introduced ‘quantum chemistry aided retrosynthetic analysis’ (QCaRA), which uses quantum chemical calculations to search systematically for decomposition paths of the target product and propose a synthesis method. However, until now, no new reactions suggested by QCaRA have been reported to lead to experimental discoveries. Using a difluoroglycine derivative as a target, this study investigated the ability of QCaRA to suggest various synthetic paths to the target without relying on previous data or the knowledge and experience of chemists. Furthermore, experimental verification of the seemingly most promising path led to the discovery of a synthesis method for the difluoroglycine derivative. The extent of the hands-on expertise of chemists required during the verification process was also evaluated. These insights are expected to advance the applicability of QCaRA to the discovery of viable experimental synthetic routes.


2020 ◽  
Author(s):  
Tsuyoshi Mita ◽  
Yu Harabuchi ◽  
Satoshi Maeda

The systematic exploration of synthetic pathways to afford a desired product through quantum chemical calculations remains a considerable challenge. In 2013, Maeda et al. introduced ‘quantum chemistry aided retrosynthetic analysis’ (QCaRA), which uses quantum chemical calculations to search systematically for decomposition paths of the target product and propose a synthesis method. However, until now, no new reactions suggested by QCaRA have been reported to lead to experimental discoveries. Using a difluoroglycine derivative as a target, this study investigated the ability of QCaRA to suggest various synthetic paths to the target without relying on previous data or the knowledge and experience of chemists. Furthermore, experimental verification of the seemingly most promising path led to the discovery of a synthesis method for the difluoroglycine derivative. The extent of the hands-on expertise of chemists required during the verification process was also evaluated. These insights are expected to advance the applicability of QCaRA to the discovery of viable experimental synthetic routes.


2020 ◽  
Author(s):  
Bapurao Bhoge ◽  
Ishu Saraogi

Chemo- and site-specific modifications in oligonucleotides have wide applicability as mechanistic probes in chemical biology. Here we have employed a classical reaction in organic chemistry, reductive amination, to selectively functionalize the N<sup>2</sup>-amine of guanine/2’-deoxyguanine monophosphate. This method specifically modifies guanine in several tested DNA oligonucleotides, while leaving the other bases unaffected. Using this approach, we have successfully incorporated desired handles chemoselectively into DNA oligomers.


2018 ◽  
Author(s):  
Tanner C. Jankins ◽  
Robert R. Fayzullin ◽  
Eugene Khaskin

We report a one-step, Ru(II)-catalyzed cyclopropanation reaction that is conceptually different from the previously reported protocols that include Corey-Chaykovsky, Simmons-Smith, and metal catalyzed carbene attack on olefins. Under the current protocol, various alcohols are transformed into sulfone substituted cyclopropanes with excellent isolated yields and diastereoselectivities. This new reaction forms highly congested cyclopropane products with three new C–C bonds, three or two new chiral centers and one new quaternary carbon center. 22 examples of isolated substrates are given. Previously reported synthetic routes for similar substrates are all multi-step, linear routes that proceed with overall low yields and poor control of stereochemistry. Experimental mechanistic investigations suggest initial metal-catalyzed dehydrogenation of the alcohol substrate and catalyst independent stepwise attack of two equivalents of sulfone on the aldehyde under basic conditions. While the Ru(II) is only responsible for the initial dehydrogenation step, the rate of aldehyde formation is crucial to maintaining the right balance of intermediates needed to afford the cyclopropane product.


2020 ◽  
Vol 27 ◽  
Author(s):  
Alessia Catalano ◽  
Carlo Franchini ◽  
Alessia Carocci

: Mexiletine is an antiarrhythmic drug belonging to IB class, acting as sodium channel blocker. Besides its well-known activity on arrhythmias, its usefulness in the treatment of myotonia, myotonic distrophy and amyotrophic lateral sclerosis is now widely recognized. Nevertheless, it has been retired from the market in several countries because of its undesired effects. Thus, several papers were reported in the last years about analogues and homologues of mexiletine being endowed with a wider therapeutic ratio and a more selectivity of action. Some of them showed sodium channel blocking activity higher than the parent compound. It is noteworthy that mexiletine is used in therapy as a racemate even though a difference in the activities of the two enantiomers were widely demonstrated, with (–)-(R)-enantiomer being more active: this finding led several research groups to study mexiletine and its analogues and homologues in their optically active forms. This review summarizes the different synthetic routes used to obtain these compounds. They could represent an interesting starting point to new mexiletine-like compounds without common side effects related to the use of mexiletine.


2020 ◽  
Vol 23 (26) ◽  
pp. 2960-2968
Author(s):  
Renáta Kertiné Ferenczi ◽  
Tünde-Zita Illyés ◽  
Sándor Balázs Király ◽  
Gyula Hoffka ◽  
László Szilágyi ◽  
...  

The reported enantioselective synthesis for the preparation of (+)-(2R,3R)-2-(4- hydroxy-3-methoxyphenyl)-3-hydroxymethyl-1,4-benzodioxane-6-carbaldehyde, precursor for the stereoselective synthesis of bioactive flavanolignans, could not be reproduced. Thus, the target molecule was prepared via the synthesis and separation of diastereomeric O-glucosides. TDDFT-ECD calculations and the 1,4-benzodioxane helicity rule were utilized to determine the absolute configuration. ECD calculations also confirmed that the 1Lb Cotton effect is governed by the helicity of the heteroring, while the higher-energy ECD transitions reflect mainly the orientation of the equatorial C-2 aryl group.


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