scholarly journals One-step catalytic asymmetric synthesis of all-syn deoxypropionate motif from propylene: Total synthesis of (2R,4R,6R,8R)-2,4,6,8-tetramethyldecanoic acid

2016 ◽  
Vol 113 (11) ◽  
pp. 2857-2861 ◽  
Author(s):  
Yusuke Ota ◽  
Toshiki Murayama ◽  
Kyoko Nozaki
Keyword(s):  
Building Blocks ◽  
Single Step ◽  
Enzymatic Reactions ◽  
Stereogenic Centers ◽  
Complex Building ◽  
One Step ◽  
Simple Molecules ◽  
Catalyzed Reactions ◽  
Enzyme Catalyzed Reactions ◽  
Major Acid

In nature, many complex structures are assembled from simple molecules by a series of tailored enzyme-catalyzed reactions. One representative example is the deoxypropionate motif, an alternately methylated alkyl chain containing multiple stereogenic centers, which is biosynthesized by a series of enzymatic reactions from simple building blocks. In organic synthesis, however, the majority of the reported routes require the syntheses of complex building blocks. Furthermore, multistep reactions with individual purifications are required at each elongation. Here we show the construction of the deoxypropionate structure from propylene in a single step to achieve a three-step synthesis of (2R,4R,6R,8R)-2,4,6,8-tetramethyldecanoic acid, a major acid component of a preen-gland wax of the graylag goose. To realize this strategy, we focused on the coordinative chain transfer polymerization and optimized the reaction condition to afford a stereo-controlled oligomer, which is contrastive to the other synthetic strategies developed to date that require 3–6 steps per unit, with unavoidable byproduct generation. Furthermore, multiple oligomers with different number of deoxypropionate units were isolated from one batch, showing application to the construction of library. Our strategy opens the door for facile synthetic routes toward other natural products that share the deoxypropionate motif.

Design of an in vitro biocatalytic cascade for the manufacture of islatravir

Science ◽  
2019 ◽  
Vol 366 (6470) ◽  
pp. 1255-1259 ◽  
Author(s):  
Mark A. Huffman ◽  
Anna Fryszkowska ◽  
Oscar Alvizo ◽  
Margie Borra-Garske ◽  
Kevin R. Campos ◽  
...  
Keyword(s):  
Chemical Synthesis ◽  
Directed Evolution ◽  
Building Blocks ◽  
Hiv Treatment ◽  
Pharmaceutical Manufacturing ◽  
Enzymatic Reactions ◽  
Catalyzed Reactions ◽  
Enzyme Catalyzed Reactions

Enzyme-catalyzed reactions have begun to transform pharmaceutical manufacturing, offering levels of selectivity and tunability that can dramatically improve chemical synthesis. Combining enzymatic reactions into multistep biocatalytic cascades brings additional benefits. Cascades avoid the waste generated by purification of intermediates. They also allow reactions to be linked together to overcome an unfavorable equilibrium or avoid the accumulation of unstable or inhibitory intermediates. We report an in vitro biocatalytic cascade synthesis of the investigational HIV treatment islatravir. Five enzymes were engineered through directed evolution to act on non-natural substrates. These were combined with four auxiliary enzymes to construct islatravir from simple building blocks in a three-step biocatalytic cascade. The overall synthesis requires fewer than half the number of steps of the previously reported routes.

Enantioselective synthesis of structurally intricate and complementary polyoxygenated building blocks of Spongistatin 1 (Altohyrtin A)

2009 ◽  
Vol 74 (5) ◽  
pp. 651-769 ◽  
Author(s):  
Alain Braun ◽  
Il Hwan Cho ◽  
Stephane Ciblat ◽  
Dean Clyne ◽  
Pat Forgione ◽  
...  
Keyword(s):  
Suzuki Coupling ◽  
Building Blocks ◽  
Enantioselective Synthesis ◽  
Side Chain ◽  
Spongistatin 1 ◽  
Enantiomerically Pure ◽  
Altohyrtin A ◽  
Stereogenic Centers ◽  
Complex Building ◽  
Synthetic Effort

Enantioselective approaches to the construction of four complex building blocks of the structurally intricate marine macrolide known as spongistatin 1 are presented. The first phase of the synthetic effort relies on a practical approach to a desymmetrized, enantiomerically pure spiroketal ring system incorporating rings A and B. Concurrently, the C17–C28 subunit, which houses one-fifth of the stereogenic centers of the target in the form of rings C and D, was assembled via a composite of stereocontrolled aldol condensations. Once arrival at the entire C1–C28 sector had been realized, routes were devised to provide two additional highly functionalized sectors consisting of C29–C44 and C38–C51. A series of subsequent transformations including cyclization of the E ring and hydroboration to afford the B-alkyl intermediate for the key Suzuki coupling to append the side chain took advantage of efficient stereocontrol. Ultimately, complete assembly and functionalization of the western EF sector of spongistatin was thwarted by an inoperative Suzuki coupling step intended to join the side chain to the C29–C44 sector, and later because of complications due to protecting groups, which precluded the complete elaboration of the late stage C29–C51 intermediate.

scholarly journals Ionic liquids as (co)solvents for enzymatic reactions

2006 ◽  
Vol 12 (3) ◽  
pp. 181-186 ◽  
Author(s):  
Muzafera Paljevac ◽  
Maja Habulin ◽  
Zeljko Knez
Keyword(s):  
Ionic Liquid ◽  
Ionic Liquids ◽  
Immobilized Lipase ◽  
Rhizomucor Miehei ◽  
Reaction Rates ◽  
Synthetic Activity ◽  
Enzymatic Reactions ◽  
Lipozyme Rm Im ◽  
Catalyzed Reactions ◽  
Enzyme Catalyzed Reactions

Ionic liquids are low melting point salts that represent an exciting new class of reaction solvents. Many reactions show advantages when carried out in ionic liquids, either with regard to enhanced reaction rates, improved selectivity, or easier reuse of catalysts. To ascertain the influence of ionic liquids on the enzyme activity, three different ionic liquids 1-butyl-3-methylimidazolium chloride ([bmim] [CI]) 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim] [PF6]) and 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF4]) were synthesized and investigated as potential media for the hydrolysis of carboxymethyl cellulose, catalyzed by non-immobilized cellulase from Humicola insolens (Celluzyme 0,7T) and for ester synthesis, catalyzed by immobilized lipase from Rhizomucor miehei (Lipozyme RM IM). Enzyme-catalyzed reactions were performed in a batch stirred reactor at atmospheric pressure. Celluzyme 0,7T showed better activity in hydrophobic ionic liquid ([bmim] [PF6]), as compared to hydrophilic ionic liquid ([bmim] [BF4]). In the case of Lipozyme RM IM, the synthetic activity of the enzyme was strongly reduced by incubating the enzyme in ionic liquids.

Recent Advance in Organocatalyzed Asymmetric Reduction of Prochiral Ketones: An Update

Synthesis ◽  
2021 ◽  
Author(s):  
Xu-Long Qin ◽  
Li-Jun Xu ◽  
Fu-She Han
Keyword(s):  
Asymmetric Reduction ◽  
Building Blocks ◽  
Short Review ◽  
Chiral Alcohols ◽  
Comprehensive Overview ◽  
Synthetic Intermediates ◽  
Prochiral Ketones ◽  
Catalyzed Reactions ◽  
Enzyme Catalyzed Reactions ◽  
Easy Operation

Chiral alcohols are important synthetic intermediates or building blocks for the diverse synthesis of drugs, agrochemicals, and natural products. Asymmetric reduction of prochiral ketones has been the most popularly investigated method for accessing chiral alcohols. In this regard, the organocatalyzed asymmetric reduction as a complementary of transition-metal- and enzyme-catalyzed reactions have attracted tremendous interest in the past decades due to the nature of metal-free and easy operation, as well as, principly, the ease of recovery and reuse of catalysts. Following up a comprehensive overview on organocatalyzed asymmetric reduction of prochiral ketones in early 2018, this short review is intended to summarize the recent progress in this area from the beginning of the year 2018 to the end of Aug. 2021.

scholarly journals Factors like Dilution and Mixing Influence Enzymatic Reactions

2020 ◽  
Vol 19 (4) ◽  
Author(s):  
Mahin Basha Syed ◽  
Venkatanagraraju Erumalla
Keyword(s):  
Enzyme Activity ◽  
Substrate Concentration ◽  
Enzymatic Reaction ◽  
Enzyme Reaction ◽  
Enzyme Concentration ◽  
Enzymatic Reactions ◽  
First Report ◽  
Enzyme Substrate ◽  
Catalyzed Reactions ◽  
Enzyme Catalyzed Reactions

Enzyme-catalyzed reactions were influenced by many factors. The enzyme reacts with the substrate and converts it into products. Enzymes are influenced by temperature, pH, enzyme concentration, and substrate concentration. This paper evaluates the hypothesis of factors that may influence enzyme activity. Two more factors that affects enzyme activity are dilution and mixing. In enzyme-substrate reactions, the small amount of dilution and mixing will not affect the enzyme activity. Dilution and mixing do not slowdowns the enzyme reaction but it enhances the enzymatic reaction up to a certain limit. Increase in dilution results in less interaction of enzyme substrate, which causes a decrease in the rate of reactions. To the best of our knowledge, this is the first report to shows that, factors like mixing and dilution also affect enzyme and substrate reactions.

scholarly journals Formation Mechanism and Biomedical Applications of Protease-Manipulated Peptide Assemblies

2021 ◽  
Vol 9 ◽  
Author(s):  
Tianyue Jiang ◽  
Chendan Liu ◽  
Xiao Xu ◽  
Bingfang He ◽  
Ran Mo
Keyword(s):  
Biomedical Applications ◽  
Enzymatic Catalysis ◽  
Building Blocks ◽  
Molecular Assembly ◽  
Bond Forming ◽  
Peptide Assembly ◽  
Non Covalent Interactions ◽  
Catalyzed Reactions ◽  
Enzyme Catalyzed Reactions ◽  
Matrix Construction

Exploiting enzyme-catalyzed reactions to manipulate molecular assembly has been considered as an attractive bottom-up nanofabrication approach to developing a variety of nano-, micro-, and macroscale structures. Upon enzymatic catalysis, peptides and their derivatives transform to assemblable building blocks that form ordered architecture by non-covalent interactions. The peptide assemblies with unique characteristics have great potential for applications in bionanotechnology and biomedicine. In this mini review, we describe typical mechanisms of the protease-instructed peptide assembly via bond-cleaving or bond-forming reactions, and outline biomedical applications of the peptide assemblies, such as drug depot, sustained release, controlled release, gelation-regulated cytotoxicity, and matrix construction.

Photochemical Evolution of Interstellar/Precometary Organic Material

1997 ◽  
Vol 161 ◽  
pp. 23-47 ◽  
Author(s):  
Louis J. Allamandola ◽  
Max P. Bernstein ◽  
Scott A. Sandford
Keyword(s):  
Origin Of Life ◽  
Building Blocks ◽  
Complex Species ◽  
Infrared Observations ◽  
Interstellar Ice ◽  
Polycyclic Aromatic ◽  
Ultraviolet Photolysis ◽  
The Origin Of Life ◽  
Simple Molecules ◽  
Complex Organic

AbstractInfrared observations, combined with realistic laboratory simulations, have revolutionized our understanding of interstellar ice and dust, the building blocks of comets. Since comets are thought to be a major source of the volatiles on the primative earth, their organic inventory is of central importance to questions concerning the origin of life. Ices in molecular clouds contain the very simple molecules H2O, CH3OH, CO, CO2, CH4, H2, and probably some NH3and H2CO, as well as more complex species including nitriles, ketones, and esters. The evidence for these, as well as carbonrich materials such as polycyclic aromatic hydrocarbons (PAHs), microdiamonds, and amorphous carbon is briefly reviewed. This is followed by a detailed summary of interstellar/precometary ice photochemical evolution based on laboratory studies of realistic polar ice analogs. Ultraviolet photolysis of these ices produces H2, H2CO, CO2, CO, CH4, HCO, and the moderately complex organic molecules: CH3CH2OH (ethanol), HC(= O)NH2(formamide), CH3C(= O)NH2(acetamide), R-CN (nitriles), and hexamethylenetetramine (HMT, C6H12N4), as well as more complex species including polyoxymethylene and related species (POMs), amides, and ketones. The ready formation of these organic species from simple starting mixtures, the ice chemistry that ensues when these ices are mildly warmed, plus the observation that the more complex refractory photoproducts show lipid-like behavior and readily self organize into droplets upon exposure to liquid water suggest that comets may have played an important role in the origin of life.

A kinetic analysis of coupled sequential enzyme reactions

2018 ◽  
Author(s):  
Justin Eilertsen ◽  
Santiago Schnell
Keyword(s):  
Enzyme Assay ◽  
Sequential Reaction ◽  
Enzyme Reactions ◽  
Indicator Reaction ◽  
Single Substrate ◽  
Complex Sequences ◽  
Catalyzed Reactions ◽  
Enzyme Catalyzed Reactions ◽  
Single Enzyme

<div>As a case study, we consider a coupled enzyme assay of sequential enzyme reactions obeying the Michaelis--Menten reaction mechanism. The sequential reaction consists of a single-substrate, single-enzyme non-observable reaction followed by another single-substrate, single-enzyme observable reaction (indicator reaction). In this assay, the product of the non-observable reaction becomes the substrate of the indicator reaction. A mathematical analysis of the reaction kinetics is performed, and it is found that after an initial fast transient, the sequential reaction is described by a pair of interacting Michaelis--Menten equations. Timescales that approximate the respective lengths of the indicator and non-observable reactions, as well as conditions for the validity of the Michaelis--Menten equations are derived. The theory can be extended to deal with more complex sequences of enzyme catalyzed reactions.</div>

A kinetic analysis of coupled sequential enzyme reactions

2018 ◽  
Author(s):  
Justin Eilertsen ◽  
Santiago Schnell
Keyword(s):  
Enzyme Assay ◽  
Sequential Reaction ◽  
Enzyme Reactions ◽  
Indicator Reaction ◽  
Single Substrate ◽  
Complex Sequences ◽  
Catalyzed Reactions ◽  
Enzyme Catalyzed Reactions ◽  
Single Enzyme

<div>As a case study, we consider a coupled enzyme assay of sequential enzyme reactions obeying the Michaelis-Menten reaction mechanism. The sequential reaction consists of a single-substrate, single enzyme non-observable reaction followed by another single-substrate, single enzyme observable reaction (indicator reaction). In this assay, the product of the non-observable reaction becomes the substrate of the indicator reaction. A mathematical analysis of the reaction kinetics is performed, and it is found that after an initial fast transient, the sequential reaction is described by a pair of interacting Michaelis-Menten equations. Timescales that approximate the respective lengths of the indicator and non-observable reactions, as well as conditions for the validity of the Michaelis-Menten equations are derived. The theory can be extended to deal with more complex sequences of enzyme catalyzed reactions.</div>

Computationally Augmented Retrosynthesis: Total Synthesis of Paspaline A and Emindole PB

2018 ◽  
Author(s):  
Timothy Newhouse ◽  
Daria E. Kim ◽  
Joshua E. Zweig
Keyword(s):  
Chemical Synthesis ◽  
Total Synthesis ◽  
Small Molecules ◽  
First Principles ◽  
Quantum Chemical ◽  
Computational Analysis ◽  
Empirical Evaluation ◽  
Synthetic Strategy ◽  
Catalyzed Reactions ◽  
Enzyme Catalyzed Reactions

The diverse molecular architectures of terpene natural products are assembled by exquisite enzyme-catalyzed reactions. Successful recapitulation of these transformations using chemical synthesis is hard to predict from first principles and therefore challenging to execute. A means of evaluating the feasibility of such chemical reactions would greatly enable the development of concise syntheses of complex small molecules. Herein, we report the computational analysis of the energetic favorability of a key bio-inspired transformation, which we use to inform our synthetic strategy. This approach was applied to synthesize two constituents of the historically challenging indole diterpenoid class, resulting in a concise route to (–)-paspaline A in 9 steps from commercially available materials and the first pathway to and structural confirmation of emindole PB in 13 steps. This work highlights how traditional retrosynthetic design can be augmented with quantum chemical calculations to reveal energetically feasible synthetic disconnections, minimizing time-consuming and expensive empirical evaluation.

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