scholarly journals Enzymatic spiroketal formation via oxidative rearrangement of pentangular polyketides

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Britta Frensch ◽  
Thorsten Lechtenberg ◽  
Michel Kather ◽  
Zeynep Yunt ◽  
Martin Betschart ◽  
...  
Keyword(s):  
Structural Complexity ◽  
Dna Helicase ◽  
Hiv Reverse Transcriptase ◽  
One Pot ◽  
Enzymatic Production ◽  
Aromatic Polyketides ◽  
Oxidative Rearrangement ◽  
Polycyclic Aromatic ◽  
The One

AbstractThe structural complexity and bioactivity of natural products often depend on enzymatic redox tailoring steps. This is exemplified by the generation of the bisbenzannulated [5,6]-spiroketal pharmacophore in the bacterial rubromycin family of aromatic polyketides, which exhibit a wide array of bioactivities such as the inhibition of HIV reverse transcriptase or DNA helicase. Here we elucidate the complex flavoenzyme-driven formation of the rubromycin pharmacophore that is markedly distinct from conventional (bio)synthetic strategies for spiroketal formation. Accordingly, a polycyclic aromatic precursor undergoes extensive enzymatic oxidative rearrangement catalyzed by two flavoprotein monooxygenases and a flavoprotein oxidase that ultimately results in a drastic distortion of the carbon skeleton. The one-pot in vitro reconstitution of the key enzymatic steps as well as the comprehensive characterization of reactive intermediates allow to unravel the intricate underlying reactions, during which four carbon-carbon bonds are broken and two CO2 become eliminated. This work provides detailed insight into perplexing redox tailoring enzymology that sets the stage for the (chemo)enzymatic production and bioengineering of bioactive spiroketal-containing polyketides.

PTSA-Catalyzed One Pot Domino Synthesis of Dihydropyrido[2,3-d]pyrimidine Derivatives and their Antimicrobial Activity

2021 ◽  
Vol 6 (3) ◽  
pp. 222-227
Author(s):  
Krishna A. Bhensdadia ◽  
Prakash L. Kalavadiya ◽  
Nilam H. Lalavani ◽  
Shipra H. Baluja
Keyword(s):  
Antimicrobial Activity ◽  
Spectral Analysis ◽  
Pyrimidine Derivatives ◽  
One Pot ◽  
In Vitro Antimicrobial Activity ◽  
Aryl Aldehydes ◽  
Three Component Reaction ◽  
The One

A novel series of dihydropyrido[2,3-d]pyrimidine derivatives were synthesized by multicomponent domino cyclization via the one-pot three component reaction of 6-amino uracil, substituted aryl aldehydes and N-methyl-1-(methylthio)-2-nitroethenamine in the presence of PTSA 10 mol% as a catalyst. The structures of these synthesized compounds were characterized by spectral analysis. Further the synthesized compounds screened for in vitro antimicrobial activity. Among all the compounds, compound 4b containing flouro substitution exhibited good inhibition against the tested species.

scholarly journals Microwave Assisted One Pot Synthesis of Tetrazole Based 3-hydroxy-4H-chromen-4-ones by modified Algar-Flynn-Oyamada reaction and their Antimicrobial activity

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
ASHOK DONGAMANTI ◽  
Nagaraju Nalaparaju ◽  
Sarasija Madderla ◽  
Vijaya Lakshmi Bommidi
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Activity ◽  
Klebsiella Pneumonia ◽  
Good Activity ◽  
One Pot ◽  
Microwave Assisted ◽  
One Pot Synthesis ◽  
Antimicrobial Studies ◽  
The One

In the present work, we report the one pot synthesis of tetrazole based 3-hydroxy-4H-chromen-4-ones 3(a-g) from  4-(1H-tetrazol-5-yl)benzaldehyde and 2-hydroxy acetophenone using KOH and H2O2 by modified Algar-Flynn-Oyamada reaction under conventional and microwave irradiation conditions. In this technique, flavonols are synthesized without isolating chalcones, in good yields. All the synthesized compounds were characterized by IR, NMR, MS and elemental. All newly synthesized compounds were screened for their in-vitro antimicrobial activity against strains such as Staphylococcus aurous, Bacillus subtilis, Klebsiella pneumonia, Escherichia coli, Aspergillus Niger, Aspergillus flavus, and Fusarium oxysporum. The results of antimicrobial studies revealed that most of the compounds exhibit good activity.

scholarly journals Designing Modular Cell-free Systems for Tunable Biotransformation of l-phenylalanine to Aromatic Compounds

2021 ◽  
Vol 9 ◽  
Author(s):  
Chen Yang ◽  
Yushi Liu ◽  
Wan-Qiu Liu ◽  
Changzhu Wu ◽  
Jian Li
Keyword(s):  
Aromatic Compounds ◽  
Value Added ◽  
Resource Limitation ◽  
Biosynthetic Pathways ◽  
One Pot ◽  
Conversion Rates ◽  
The One ◽  
Free Modules ◽  
Enzymatic Pathways

Cell-free systems have been used to synthesize chemicals by reconstitution of in vitro expressed enzymes. However, coexpression of multiple enzymes to reconstitute long enzymatic pathways is often problematic due to resource limitation/competition (e.g., energy) in the one-pot cell-free reactions. To address this limitation, here we aim to design a modular, cell-free platform to construct long biosynthetic pathways for tunable synthesis of value-added aromatic compounds, using (S)-1-phenyl-1,2-ethanediol ((S)-PED) and 2-phenylethanol (2-PE) as models. Initially, all enzymes involved in the biosynthetic pathways were individually expressed by an E. coli-based cell-free protein synthesis (CFPS) system and their catalytic activities were confirmed. Then, three sets of enzymes were coexpressed in three cell-free modules and each with the ability to complete a partial pathway. Finally, the full biosynthetic pathways were reconstituted by mixing two related modules to synthesize (S)-PED and 2-PE, respectively. After optimization, the final conversion rates for (S)-PED and 2-PE reached 100 and 82.5%, respectively, based on the starting substrate of l-phenylalanine. We anticipate that the modular cell-free approach will make a possible efficient and high-yielding biosynthesis of value-added chemicals.

scholarly journals Three Multi-Components Reaction: Synthesis and X-Ray Single-Crystal of Hydroacridinone-Based Hydrazino-S-Triazine Derivative as a New Class of Urease Inhibitor

Crystals ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 14 ◽  
Author(s):  
Assem Barakat ◽  
Saied M. Soliman ◽  
Ayman El-Faham ◽  
M. Ali ◽  
Abdullah Mohammed Al-Majid ◽  
...  
Keyword(s):  
Structural Features ◽  
Acetohydroxamic Acid ◽  
Orthorhombic Crystal System ◽  
Orthorhombic Crystal ◽  
One Pot ◽  
X Ray ◽  
New Class ◽  
Hirshfeld Surfaces ◽  
The One

The one-pot fashion of three multi-component reaction provides the desired hydroacridinone-based hydrazino-s-triazine scaffold 4. Compound 4 was crystallized in an orthorhombic crystal system and Pbca space group with a = 11.6271(2) Å, b = 18.2018(4) Å, c = 32.4721(6) Å, and α = β = γ = 90° with one formula unit per asymmetric unit and eight molecules per unit cell. Additionally, structural features, Hirshfeld surfaces, and DFT studies were also investigated. Its packing in the crystal is controlled by H…H (63.4%), O…H (12.7%), Cl…H (7.2%), N…H (4.7%), and C…H (10.2%) contacts, where the O…H and Cl…H contacts were found the strongest. In vitro urease inhibition evaluation showed that the hydroacridinone-based hydrazino-s-triazine is more active (IC50 = 17.9 ± 0.47 µM) than the standard acetohydroxamic acid (IC50 = 20.3 ± 0.43 µM).

scholarly journals 2-Ketoglutarate-Generated In Vitro Enzymatic Biosystem Facilitates Fe(II)/2-Ketoglutarate-Dependent Dioxygenase-Mediated C–H Bond Oxidation for (2s,3r,4s)-4-Hydroxyisoleucine Synthesis

2020 ◽  
Vol 21 (15) ◽  
pp. 5347
Author(s):  
Xiao-Ran Jing ◽  
Huan Liu ◽  
Yao Nie ◽  
Yan Xu
Keyword(s):  
Amino Acids ◽  
Raw Materials ◽  
Cascade Reaction ◽  
Single Step ◽  
One Pot ◽  
Bond Functionalization ◽  
Hydroxy Amino ◽  
Enzymatic Systems ◽  
The One

Fe(II)/2-ketoglutarate-dependent dioxygenase (Fe(II)/2-KG DO)-mediated hydroxylation is a critical type of C–H bond functionalization for synthesizing hydroxy amino acids used as pharmaceutical raw materials and precursors. However, DO activity requires 2-ketoglutarate (2-KG), lack of which reduces the efficiency of Fe(II)/2-KG DO-mediated hydroxylation. Here, we conducted multi-enzymatic syntheses of hydroxy amino acids. Using (2s,3r,4s)-4-hydroxyisoleucine (4-HIL) as a model product, we coupled regio- and stereo-selective hydroxylation of l-Ile by the dioxygenase IDO with 2-KG generation from readily available l-Glu by l-glutamate oxidase (LGOX) and catalase (CAT). In the one-pot system, H2O2 significantly inhibited IDO activity and elevated Fe2+ concentrations of severely repressed LGOX. A sequential cascade reaction was preferable to a single-step process as CAT in the former system hydrolyzed H2O2. We obtained 465 mM 4-HIL at 93% yield in the two-step system. Moreover, this process facilitated C–H hydroxylation of several hydrophobic aliphatic amino acids to produce hydroxy amino acids, and C–H sulfoxidation of sulfur-containing l-amino acids to yield l-amino acid sulfoxides. Thus, we constructed an efficient cascade reaction to produce 4-HIL by providing prerequisite 2-KG from cheap and plentiful l-Glu and developed a strategy for creating enzymatic systems catalyzing 2-KG-dependent reactions in sustainable bioprocesses that synthesize other functional compounds.

Artificial in Vitro Synthetic Enzymatic Biosystem for the One-Pot Sustainable Biomanufacturing of Glucosamine from Starch and Inorganic Ammonia

ACS Catalysis ◽  
2020 ◽  
Vol 10 (23) ◽  
pp. 13809-13819
Author(s):  
Dongdong Meng ◽  
Xinlei Wei ◽  
Xue Bai ◽  
Wei Zhou ◽  
Chun You
Keyword(s):  
One Pot ◽  
The One

scholarly journals One-Pot Multicomponent Synthesis of Methoxybenzo[h]quinoline-3-carbonitrile Derivatives; Anti-Chagas, X-ray, and In Silico ADME/Tox Profiling Studies

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6977
Author(s):  
Hegira Ramírez ◽  
Katiuska Charris ◽  
Esteban Fernandez-Moreira ◽  
Benjamín Nogueda-Torres ◽  
Mario V. Capparelli ◽  
...  
Keyword(s):  
In Silico ◽  
Ammonium Acetate ◽  
Aromatic Aldehydes ◽  
Multicomponent Synthesis ◽  
Activity Profile ◽  
One Pot ◽  
X Ray ◽  
Elemental Analyses ◽  
The One

Several methoxybenzo[h]quinoline-3-carbonitrile analogs were designed and synthesized in a repositioning approach to developing compounds with anti-prostate cancer and anti-Chagas disease properties. The compounds were synthesized through a sequential multicomponent reaction of aromatic aldehydes, malononitrile, and 1-tetralone in the presence of ammonium acetate and acetic acid (catalytic). The effect of the one-pot method on the generation of the target product has been studied. The compounds were in vitro screened against bloodstream trypomastigotes of T. cruzi (NINOA and INC-5 strains) and were most effective at showing a better activity profile than nifurtimox and benznidazole (reference drugs). A study in silico on absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) profiling to help describe the molecular properties related to the pharmacokinetic aspects in the human body of these compounds was reported. In addition, X-ray data for the compound 2-Amino-5,6-dihydro-4-(3-hydroxy-4-methoxy-phenyl)-8-methoxybenzo[h]quinoline-3-carbonitrile 6 was being reported. Spectral (IR, NMR, and elemental analyses) data on all final compounds were consistent with the proposed structures.

Mild and efficient 64Cu labeling of perhydro-1, 4-diazepine derivatives for potential use with large peptides, proteins and antibodies

2020 ◽  
Vol 108 (7) ◽  
pp. 555-563 ◽  
Author(s):  
Lukas Greifenstein ◽  
Denise Späth ◽  
Jean Phillip Sinnes ◽  
Tilmann Grus ◽  
Frank Rösch
Keyword(s):  
Energy Barrier ◽  
Radioactive Isotope ◽  
One Pot ◽  
One Pot Synthesis ◽  
Novel Approach ◽  
The One ◽  
Cyclic Part ◽  
Potential Use

AbstractDATA (6-Amino-1,4-diazapine-triacetate) and AAZTA (6-Amino-1,4-diazapine-tetracetate) chelators represent a novel approach representing hybrid-chelates: possessing significant cyclic and acyclic character. It is believed that flexibility of the acyclic part facilitates rapid complexation, whilst the preorganized cyclic part minimizes the energy barrier to complexation and inhibits decomplexation processes. So far, these chelators have been used exclusively with 44Sc and 68Ga only. Recent results with natCu predict high stabilities for Cu-AAZTA, yet no radioactive labeling of AAZTA or DATA with 64Cu or any additional radioactive isotope has been reported. We present the one pot synthesis of the bifunctional derivatives AAZTA5OMe and DATA5mOMe and their labeling with 64Cu. In addition, in vitro stability of the respective complexes are presented.

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