Extending Synthetic Routes for Oligosaccharides by Enzyme, Substrate and Reaction Engineering

2010 ◽  
pp. 163-193 ◽  
Author(s):  
Jürgen Seibel ◽  
Hans-Joachim Jördening ◽  
Klaus Buchholz
Keyword(s):  
Reaction Engineering ◽  
Enzyme Substrate ◽  
Synthetic Routes

Discovery of a Difluoroglycine Synthesis Method through Quantum Chemical Calculations

2020 ◽  
Author(s):  
Tsuyoshi Mita ◽  
Yu Harabuchi ◽  
Satoshi Maeda
Keyword(s):  
Quantum Chemical Calculations ◽  
Experimental Verification ◽  
Quantum Chemical ◽  
Synthesis Method ◽  
Target Product ◽  
Systematic Exploration ◽  
Hands On ◽  
Retrosynthetic Analysis ◽  
Synthetic Routes ◽  
Verification Process

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.

Discovery of a Difluoroglycine Synthesis Method through Quantum Chemical Calculations

2020 ◽  
Author(s):  
Tsuyoshi Mita ◽  
Yu Harabuchi ◽  
Satoshi Maeda
Keyword(s):  
Quantum Chemical Calculations ◽  
Experimental Verification ◽  
Quantum Chemical ◽  
Synthesis Method ◽  
Target Product ◽  
Systematic Exploration ◽  
Hands On ◽  
Retrosynthetic Analysis ◽  
Synthetic Routes ◽  
Verification Process

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.

Three-Component [1+1+1] Cyclopropanation with Ruthenium(II)

2018 ◽  
Author(s):  
Tanner C. Jankins ◽  
Robert R. Fayzullin ◽  
Eugene Khaskin
Keyword(s):  
Quaternary Carbon ◽  
Poor Control ◽  
One Step ◽  
Synthetic Routes ◽  
Mechanistic Investigations ◽  
Chiral Centers ◽  
Metal Catalyzed ◽  
The Right ◽  
Substituted Cyclopropanes

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.

Cell-Specific Chemical Delivery Using a Selective Nitroreductase–Nitroaryl Pair

2018 ◽  
Author(s):  
Todd D. Gruber ◽  
Chithra Krishnamurthy ◽  
Jonathan B. Grimm ◽  
Michael R. Tadross ◽  
Laura M. Wysocki ◽  
...  
Keyword(s):  
Small Molecules ◽  
Mammalian Cells ◽  
Target Cells ◽  
Specific Chemical ◽  
E Coli ◽  
Enzyme Substrate ◽  
Cell Specificity ◽  
General Chemical ◽  
Increased Activity ◽  
Enzyme Variant

<p>The utility of<b> </b>small molecules to probe or perturb biological systems is limited by the lack of cell-specificity. ‘Masking’ the activity of small molecules using a general chemical modification and ‘unmasking’ it only within target cells could overcome this limitation. To this end, we have developed a selective enzyme–substrate pair consisting of engineered variants of <i>E. coli</i> nitroreductase (NTR) and a 2‑nitro-<i>N</i>-methylimidazolyl (NM) masking group. To discover and optimize this NTR–NM system, we synthesized a series of fluorogenic substrates containing different nitroaromatic masking groups, confirmed their stability in cells, and identified the best substrate for NTR. We then engineered the enzyme for improved activity in mammalian cells, ultimately yielding an enzyme variant (enhanced NTR, or eNTR) that possesses up to 100-fold increased activity over wild-type NTR. These improved NTR enzymes combined with the optimal NM masking group enable rapid, selective unmasking of dyes, indicators, and drugs to genetically defined populations of cells.</p>

Voltage Gated Sodium Channel Blockers: Synthesis of Mexiletine Analogues and Homologues

2020 ◽  
Vol 27 ◽  
Author(s):  
Alessia Catalano ◽  
Carlo Franchini ◽  
Alessia Carocci
Keyword(s):  
Sodium Channel ◽  
Channel Blocker ◽  
Parent Compound ◽  
Channel Blockers ◽  
Sodium Channel Blocker ◽  
Starting Point ◽  
Channel Blocking ◽  
Blocking Activity ◽  
Synthetic Routes ◽  
Lateral Sclerosis

: 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.

Evaluation of Different Synthetic Routes to (2R,3R)-3-Hydroxymethyl-2-(4-hydroxy- 3-methoxyphenyl)-1,4-Benzodioxane-6-Carbaldehyde

2020 ◽  
Vol 23 (26) ◽  
pp. 2960-2968
Author(s):  
Renáta Kertiné Ferenczi ◽  
Tünde-Zita Illyés ◽  
Sándor Balázs Király ◽  
Gyula Hoffka ◽  
László Szilágyi ◽  
...  
Keyword(s):  
Absolute Configuration ◽  
Stereoselective Synthesis ◽  
Cotton Effect ◽  
Enantioselective Synthesis ◽  
Aryl Group ◽  
Target Molecule ◽  
Synthetic Routes ◽  
The Absolute

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.

Synthetic Routes to 2-Iminothiazolidines: State-of-the-Art 2006-2020

2020 ◽  
Vol 24 (24) ◽  
pp. 2823-2844
Author(s):  
Aditya Bhattacharyya
Keyword(s):  
State Of The Art ◽  
Biological Significance ◽  
Review Article ◽  
Synthetic Methods ◽  
Pharmacological Properties ◽  
Cyclic Molecules ◽  
Synthetic Routes

: Multiheteroatom-containing small-sized cyclic molecules such as 2- iminothiazolidines are often found to possess beneficial pharmacological properties. In this review article, the biological significance of 2-iminothiazolidines is discussed and the literature reports published in the last 15 years spanning from 2006 to 2020 describing various preparative routes to access 2-iminothiazolidine derivatives have been categorically and chronologically described. The notable synthetic methods discussed here involve ringexpansion transformations of nonactivated and activated aziridines, thiiranes, epoxides, and other miscellaneous reactions.

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