β-Substituted γ-butyrolactams from mucochloric acid: synthesis of (±)-baclofen and other γ-aminobutyric acids and useful building blocks

RSC Advances ◽  
2014 ◽  
Vol 4 (5) ◽  
pp. 2538-2545 ◽  
Author(s):  
Kallolmay Biswas ◽  
Rajesh Gholap ◽  
Padakanti Srinivas ◽  
Sachin Kanyal ◽  
Koushik Das Sarma
Keyword(s):  
Building Blocks ◽  
Acid Synthesis ◽  
Mucochloric Acid

scholarly journals Rapid approach to complex boronic acids

2019 ◽  
Vol 5 (7) ◽  
pp. eaaw4607 ◽  
Author(s):  
Constantinos G. Neochoritis ◽  
Shabnam Shaabani ◽  
Maryam Ahmadianmoghaddam ◽  
Tryfon Zarganes-Tzitzikas ◽  
Li Gao ◽  
...  
Keyword(s):  
Small Molecules ◽  
Boronic Acid ◽  
Multicomponent Reactions ◽  
Chemical Space ◽  
Building Blocks ◽  
Acid Synthesis ◽  
Success Rates ◽  
Boronic Acid Derivatives ◽  
Low Coverage ◽  
Target Synthesis

The compatibility of free boronic acid building blocks in multicomponent reactions to readily create large libraries of diverse and complex small molecules was investigated. Traditionally, boronic acid synthesis is sequential, synthetically demanding, and time-consuming, which leads to high target synthesis times and low coverage of the boronic acid chemical space. We have performed the synthesis of large libraries of boronic acid derivatives based on multiple chemistries and building blocks using acoustic dispensing technology. The synthesis was performed on a nanomole scale with high synthesis success rates. The discovery of a protease inhibitor underscores the usefulness of the approach. Our acoustic dispensing–enabled chemistry paves the way to highly accelerated synthesis and miniaturized reaction scouting, allowing access to unprecedented boronic acid libraries.

scholarly journals 6’-Fluoro[4.3.0]bicyclo nucleic acid: synthesis, biophysical properties and molecular dynamics simulations

2018 ◽  
Vol 14 ◽  
pp. 3088-3097 ◽  
Author(s):  
Sibylle Frei ◽  
Andrei Istrate ◽  
Christian J Leumann
Keyword(s):  
Molecular Dynamics ◽  
Cyclopropane Ring ◽  
Building Blocks ◽  
Acid Synthesis ◽  
Rnase H ◽  
Dynamics Simulation ◽  
Biophysical Properties ◽  
Dna And Rna ◽  
Dynamics Simulations ◽  
Thermal Melting

Here we report on the synthesis, biophysical properties and molecular modeling of oligonucleotides containing unsaturated 6’-fluoro[4.3.0]bicyclo nucleotides (6’F-bc4,3-DNA). Two 6’F-bc4,3 phosphoramidite building blocks (T and C) were synthesized starting from a previously described [3.3.0]bicyclic sugar. The conversion of this sugar to a gem-difluorinated tricyclic intermediate via difluorocarbene addition followed either by a NIS-mediated or Vorbrüggen nucleosidation yielded in both cases the β-tricyclic nucleoside as major anomer. Subsequent desilylation and cyclopropane ring opening of these tricyclic intermediates afforded the unsaturated 6’F-bc4,3 nucleosides. The successful incorporation of the corresponding phosphoramidite building blocks into oligonucleotides was achieved with tert-butyl hydroperoxide as oxidation agent. Thermal melting experiments of the modified duplexes disclosed a destabilizing effect versus DNA and RNA complements, but with a lesser degree of destabilization versus complementary DNA (ΔT m/mod = −1.5 to −3.7 °C). Molecular dynamics simulation on the nucleoside and oligonucleotide level revealed the preference of the C1’-exo/C2’-endo alignment of the furanose ring. Moreover, the simulation of duplexes with complementary RNA disclosed a DNA/RNA-type duplex structure suggesting that this modification might be a substrate for RNase H.

scholarly journals Adenosine: a partially discovered medicinal agent

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Rohit Batra ◽  
Vinay Jain ◽  
Pankaj Sharma
Keyword(s):  
Immune Response ◽  
Ribonucleic Acid ◽  
Viral Infections ◽  
Inflammatory Diseases ◽  
Building Blocks ◽  
Acid Synthesis ◽  
Host Immune Response ◽  
Post Traumatic Stress ◽  
Pentose Sugar ◽  
Nitrogenous Base

Abstract Background A plethora of chemicals exists in human body which can alter physiology in one way or other. Scientists have always been astounded by such abilities of chemicals but as the technology advances, even the chemical which was once expected to be well known changes its status to not really well known. Adenosine is one of the chemicals which is in consonance with the aforementioned statements, although previous articles have covered vast information on role of adenosine in cardiovascular physiology, bacterial pathophysiology and inflammatory diseases. In this review we have discussed adenosine and its congeners as potential promising agents in the treatment of Huntington’s disease, post-traumatic stress disorder, erectile dysfunction, viral infections (SARS-CoV) and anxiety. Main text Adenosine is a unique metabolite of ATP; which serves in signalling as well. It is made up of adenine (a nitrogenous base) and ribo-furanose (pentose) sugar linked by β-N9-glycosidic bond. Adenosine on two successive phosphorylation forms ATP (Adenosine Triphosphate) which is involved in several active processes of cell. It is also one of the building blocks (nucleotides) involved in DNA (Deoxy-ribonucleic Acid) and RNA (Ribonucleic Acid) synthesis. It is also a component of an enzyme called S-adenosyl-L-methionine (SAM) and cyano-cobalamin (vitamin B-12). Adenosine acts by binding to G protein-coupled receptor (GPCR: A1, A2A, A2B and A3) carries out various responses some of which are anti-platelet function, hyperaemic response, bone remodelling, involvement in penile erection and suppression of inflammation. On the other hand, certain microorganisms belonging to genus Candida, Staphylococcus and Bacillus utilize adenosine in order to escape host immune response (phagocytic clearance). These microbes evade host immune response by synthesizing and releasing adenosine (with the help of an enzyme: adenosine synthase-A), at the site of infection. Conclusion With the recent advancement in attribution of adenosine in physiology and pathological states, adenosine and its congeners are being looked forward to bringing a revolution in treatment of inflammation, viral infections, psychiatric and neurodegenerative disorders.

scholarly journals DTYMK is essential for genome integrity and neuronal survival

2021 ◽  
Author(s):  
Jo M. Vanoevelen ◽  
Jörgen Bierau ◽  
Janine C. Grashorn ◽  
Ellen Lambrichs ◽  
Erik-Jan Kamsteeg ◽  
...  
Keyword(s):  
Neurodegenerative Disease ◽  
Genome Stability ◽  
Neuronal Survival ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Cerebral Atrophy ◽  
Building Blocks ◽  
Acid Synthesis ◽  
Nucleotide Metabolism ◽  
Loss Of Function

AbstractNucleotide metabolism is a complex pathway regulating crucial cellular processes such as nucleic acid synthesis, DNA repair and proliferation. This study shows that impairment of the biosynthesis of one of the building blocks of DNA, dTTP, causes a severe, early-onset neurodegenerative disease. Here, we describe two unrelated children with bi-allelic variants in DTYMK, encoding dTMPK, which catalyzes the penultimate step in dTTP biosynthesis. The affected children show severe microcephaly and growth retardation with minimal neurodevelopment. Brain imaging revealed severe cerebral atrophy and disappearance of the basal ganglia. In cells of affected individuals, dTMPK enzyme activity was minimal, along with impaired DNA replication. In addition, we generated dtymk mutant zebrafish that replicate this phenotype of microcephaly, neuronal cell death and early lethality. An increase of ribonucleotide incorporation in the genome as well as impaired responses to DNA damage were observed in dtymk mutant zebrafish, providing novel pathophysiological insights. It is highly remarkable that this deficiency is viable as an essential component for DNA cannot be generated, since the metabolic pathway for dTTP synthesis is completely blocked. In summary, by combining genetic and biochemical approaches in multiple models we identified loss-of-function of DTYMK as the cause of a severe postnatal neurodegenerative disease and highlight the essential nature of dTTP synthesis in the maintenance of genome stability and neuronal survival.

scholarly journals Subcellular Energetics and Carbon Storage in Chlamydomonas

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1154 ◽  
Author(s):  
Burlacot ◽  
Peltier ◽  
Li-Beisson
Keyword(s):  
Energy Management ◽  
Electron Flow ◽  
Building Blocks ◽  
Acid Synthesis ◽  
Cellular Mechanisms ◽  
Algal Biotechnology ◽  
Atp Production ◽  
Holistic Understanding ◽  
Algal Photosynthesis ◽  
Biotechnology Sector

Microalgae have emerged as a promising platform for production of carbon- and energy- rich molecules, notably starch and oil. Establishing an economically viable algal biotechnology sector requires a holistic understanding of algal photosynthesis, physiology, cell cycle and metabolism. Starch/oil productivity is a combined effect of their cellular content and cell division activities. Cell growth, starch and fatty acid synthesis all require carbon building blocks and a source of energy in the form of ATP and NADPH, but with a different requirement in ATP/NADPH ratio. Thus, several cellular mechanisms have been developed by microalgae to balance ATP and NADPH supply which are essentially produced by photosynthesis. Major energy management mechanisms include ATP production by the chloroplast-based cyclic electron flow and NADPH removal by water-water cycles. Furthermore, energetic coupling between chloroplast and other cellular compartments, mitochondria and peroxisome, is increasingly recognized as an important process involved in the chloroplast redox poise. Emerging literature suggests that alterations of energy management pathways affect not only cell fitness and survival, but also influence biomass content and composition. These emerging discoveries are important steps towards diverting algal photosynthetic energy to useful products for biotechnological applications.

scholarly journals Nitrogen sourcing during viral infection of marine cyanobacteria

2019 ◽  
Vol 116 (31) ◽  
pp. 15590-15595 ◽  
Author(s):  
Jacob R. Waldbauer ◽  
Maureen L. Coleman ◽  
Adriana I. Rizzo ◽  
Kathryn L. Campbell ◽  
John Lotus ◽  
...  
Keyword(s):  
Host Cell ◽  
Isotope Labeling ◽  
De Novo ◽  
Building Blocks ◽  
Acid Synthesis ◽  
Host Protein ◽  
Dependent Manner ◽  
Host Proteins ◽  
Amino Acid Synthesis ◽  
Progeny Phage

The building blocks of a virus derived from de novo biosynthesis during infection and/or catabolism of preexisting host cell biomass, and the relative contribution of these 2 sources has important consequences for understanding viral biogeochemistry. We determined the uptake of extracellular nitrogen (N) and its biosynthetic incorporation into both virus and host proteins using an isotope-labeling proteomics approach in a model marine cyanobacterium Synechococcus WH8102 infected by a lytic cyanophage S-SM1. By supplying dissolved N as 15N postinfection, we found that proteins in progeny phage particles were composed of up to 41% extracellularly derived N, while proteins of the infected host cell showed almost no isotope incorporation, demonstrating that de novo amino acid synthesis continues during infection and contributes specifically and substantially to phage replication. The source of N for phage protein synthesis shifted over the course of infection from mostly host derived in the early stages to more medium derived later on. We show that the photosystem II reaction center proteins D1 and D2, which are auxiliary metabolic genes (AMGs) in the S-SM1 genome, are made de novo during infection in an apparently light-dependent manner. We also identified a small set of host proteins that continue to be produced during infection; the majority are homologs of AMGs in S-SM1 or other viruses, suggesting selective continuation of host protein production during infection. The continued acquisition of nutrients by the infected cell and their utilization for phage replication are significant for both evolution and biogeochemical impact of viruses.

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