Short Synthesis Research Articles

Synthesis, structural characterization of optical isomers and potential impurities in Alalevonadifloxacin mesylate

A short and efficient synthesis of three stereoisomeric and three process impurities of Alalevonadifloxacin mesylate (WCK 2349), a novel anti-methicillin-resistant Staphylococcus aureus (MRSA) antibiotic, has been disclosed. The synthesis and characterization of these impurities are discussed in detail to provide access to the reference standards for the impurity profile of the drug substance as well as the drug product. Moreover, systematic analytical method development for stereospecific separation between alalevonadifloxacin mesylate (1) and an enantiomer, WCK 6577 (2) in the presence of other process impurities for accurate quantification using liquid chromatography is also discussed.

Organocatalytic aldol approach for the protecting group-free asymmetric synthesis of (7R')-parabenzlactone, (-)-hinokinin, (-)-yatein, (-)-bursehernin, (-)-pluviatolide, (+)-isostegane and allied lignans.

A short and efficient catalytic asymmetric protection-free synthesis of dibenzylbutyrolactone lignans, such as (-)-hinokinin, (-)-yatein, (-)-bursehernin, (-)-pluviatolide, and their 7'-hydroxylignans - (7'R)-parabenzlactone, (7'R)-hydroxyyatein, (7'R)-hydroxybursehernin, and (7'R)-hydroxy pluviatolide, respectively, is described. The syntheses of (+)-isostegane and the formal synthesis of (-)-podophyllotoxin and bicubebins are also described. Organocatalytic aldol-reduction-lactonization and Pd/C-catalyzed hydrogenative debromination are two-pot sequential reactions for the enantioselective synthesis of hydroxybutyrolactone 13b with excellent diastereo- and enantioselectivity (dr 33 : 1 and >99% ee). The protecting group-free chemoselective α-alkylation of 13b directly led to 7'-hydroxydibenzylbutyrolactone lignans, followed by hydrogenative dehydroxylation, which led to their (deoxy) dibenzylbutyrolactone lignans, and the syntheses were completed in three to five steps from 6-bromopiperonal.

Short and scalable synthesis of cynandione A.

A two-step gram-scale synthesis of cynandione A is described. The key to success is the one-pot tandem oxidation/regioselective arylation of 1,4-hydroquinone in the presence of an excess amount of oxidant. Natural bond orbital charge analysis was performed in order to understand the regioselectivity of the arylation step. The highly practical and scalable synthesis developed herein is expected to assist the in-depth biological evaluation of cynandione A in various animal models.

Crystal structure and properties of anhydrous 5-nitroaminotetrazole

5-Nitraminotetrazole (5-NAT) is a high-energy and green explosive material that has attracted extensive attention due to its short synthesis steps and decomposition products consisting mainly of nitrogen and water. However, the presence of a crystal water molecule in the current crystal structure of 5-nitroaminotetrazole significantly affects its detonation performance and mechanical sensitivity. In this study, we report the successful synthesis of an anhydrous crystal form of 5-NAT through slow volatilization of an ethyl acetate solution under dry conditions. The anhydrous crystal form of 5-NAT exhibited increased density and detonation velocity compared to the monohydrate crystal form. Furthermore, quantum chemical analysis showed that the anhydrous crystal form exhibited increased sensitivity to external force stimulation due to stronger oxygen-oxygen and nitrogen-oxygen repulsion. In conclusion, the anhydrous crystal form of 5-NAT shows promise as a high-energy and green primary explosive.

Chemoselective Nozaki-Hiyama-Takai-Kishi and Grignard reaction: short synthesis of some carbahexopyranoses.

A common, divergent, efficient, stereoselective and short approach for the total syntheses of some carbahexopyranoses namely, MK7607, (-)-gabosine A, (-)-conduritol E, (-)-conduritol F, 6a-carba-β-d-fructopyranose and other carbasugars using chemoselective Grignard or Nozaki-Hiyama-Takai-Kishi (NHTK) reactions and RCM. Herein, the Grignard and NHTK reactions are able to differentiate the reactivity difference between lactol or lactolacetate and aldehyde of 2 & 6 under given conditions to give the desired skeleton chemoselectivity.

Zr-MOF membranes with ultra-fast water-selective permeation towards intensification of esterification reaction.

Well-intergrown polycrystalline UiO-66 membranes were successfully synthesized on a polymeric substrate under mild synthesis conditions of a lower temperature and short synthesis time. The resulted UiO-66 membranes with fast water selective transport channels exhibited unprecedentedly high solvent dehydration performance with a permeation flux of ∼6100 g m-2 h-1 and a separation factor of ∼7500, showing great potential for intensification of esterification reaction.

Upgrading furanic platforms to α-enaminones: tunable continuous flow hydrogenation of bio-based cyclopentenones

Continuous flow hydrogenation of trans-4,5-diamino cyclopentenones to diamino cyclopentanones and base-promoted elimination originates α-enaminones. The strategy is applied to the short synthesis of reported ATP-sensitive potassium channel agonist.

Synthesis and Evaluation of Reactive Oxygen Species Sensitive Prodrugs of a NAMPT Inhibitor FK866

NAMPT is an attractive target in cancer therapy and numerous NAMPT inhibitors have been developed. However, the clinical activities of NAMPT inhibitors have displayed disappointing results in clinical trials for their dose-limiting toxicities. In this study, reactive oxygen species (ROS)-responsive prodrugs of a NAMPT inhibitor FK866 were designed and synthesized. A short synthesis method was developed to shield the activity of FK866 through a quaternary ammonium connection. Two prodrugs, with boronic acid as a responsive group to ROS, were prepared and one of the prodrugs 122-066 also contained a fluorescence carrier. Both of the prodrugs released the active compound by the treatment of H2O2,, and the biological evaluation showed that they exhibited a higher potency in cells with high levels of ROS. Moreover, prodrug 122-066 had the ability to release FK866 and simultaneously induce the fluorescence activation under the stimulation of H2O2. This method has the potential to improve the therapeutic window of NAMPT inhibitors.

The synthesis of Broccoli RNA fluorescent aptamer in <i>Saccharomyces cerevisiae</i> yeast cells

BACKGROUND: RNA aptamers are short, single-stranded oligonucleotides, with remarkable binding ability to target molecules characterized by high specificity and affinity. Such targets are vastly diverse and range from specific ions to entire cells. RNA aptamers are widely used in biology and medicine for basic research, as well as for practical purposes as in therapy and diagnostics. At present, chemical or in vitro methods of synthesis are mainly used to obtain RNA aptamers. However, such methods are expensive and time-consuming with low productivity. Therefore, in vivo methods are becoming more attractive to researchers working on optimizing high-scale production of RNA aptamers.
 AIM: The aim of this work is to develop a reporter system for optimizing the synthesis of small RNA molecules in Saccharomyces cerevisiae yeast cells.
 MATERIALS AND METHODS: We used the Broccoli fluorescent RNA aptamer to develop a reporter system allowing us to optimize the conditions for in vivo short RNA synthesis in yeast cells. This aptamer is about 112 bp in size and binds to the fluorogenic dye DFHBI-1T. Only upon binding, the aptamer-dye complex exhibits fluorescence properties. After excitation using light with a wavelength of 482 nm, the aptamer-dye complex emission is observed with a peak at 505 nm.
 RESULTS: We have designed a reporter system providing the synthesis of the fluorescent Broccoli RNA aptamer in S. cerevisiae yeast cells. Transcription of RNA molecules containing the aptamer is carried out by the regulated promoter of the GAL1 gene. The synthesized transcripts contain the HH and HDV ribozymes to ensure precise cleavage of the RNA aptamer sequences.
 CONCLUSIONS: This reporter system is based on the Broccoli RNA aptamer, and it can be used to optimize the in vivo synthesis of RNA aptamers in S. cerevisiae yeast cells. This work serves an urgent task in connection with the active use of such aptamers in scientific research, biotechnology and medicine.

Ultra-rapid microwave-assisted synthesis of gallium doped zinc oxide for enhanced photocurrent generation

Ultra-rapid microwave-assisted hydrothermal synthesis was performed, zinc oxide nanoparticles were fabricated and doped with gallium. Different times (5, 15, and 30 min) and concentrations of doped Ga (1, 3, and 6%) were used to improve their characteristic properties. In addition, the relation between time/dopant was analyzed. The samples were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), Raman spectroscopy, and UV–Vis diffuse reflectance spectroscopy. Photoluminescence (PL) to verify number of defects. SEM analysis showed the formation of nanorods morphology even with a short synthesis time. The X-ray diffractograms and Raman spectra suggest the successful insertion of Ga into the ZnO lattice. The crystallite size obtained by doping was between 36 and 50 nm. The lattice parameters determined by the Rietveld refinement confirmed the formation of a wurtzite hexagonal structure. The band gap range found was 3.12–3.22 eV, which increases the potential of ZnO for optical applications. The presence of defects as result of doping was confirmed by PL. The microstructural changes of the material are enhanced by doping, which causes the photocurrent to increase from 0,002 to 0.012 mA/cm2 in doped ZnO. The synthesis time and Ga doping facilitated the production of ZnO nanoparticles with improved properties.

Relationship between citrus and stress, citrus and oxidative stress: a short synthesis

Relationship between citrus and stress, citrus and oxidative stress: a short synthesis

Tf2O-Promoted Morgan–Walls Reaction: From a Flexible Approach to Functionalized Phenanthridines and Quinazolines to the Short and Divergent Total Syntheses of Alkaloids

AbstractA new protocol for the direct transformation of secondary amides (N-acyl-o-xenylamines) to phenanthridines under mild conditions is reported. The method features trifluoromethanesulfonic anhydride (Tf2O)/2-fluoropyridine as the efficient amide activation system and MeCN or CH2Cl2 as the solvent. For some substrates, MeCN participated in the reaction, which affords a mild access to polysubstituted quinazolines. By employing a Tf2O/2,4,6-tri-tert-butylpyrimidine (TTBP) combination, the method was extended to an N-formyl-o-xenylamine, which represents a recalcitrant amide substrate type for the dehydrative cyclization reaction. More importantly, a one-pot method was established for the direct and divergent synthesis of four types of phenanthridinoids from o-xenylamines, which features both a tert-N-formyl-o-xenylamine and phenanthridinium salt as key and versatile intermediates. The investigation has resulted in one of the shortest and the most efficient total syntheses of the three natural products trisphaeridine, 5,6-dihydrobicolorine, and N-methylcrinasiadine, and in the formal total syntheses of three other ones: 3-hydroxytrisphaeridine, bicolorine, and zephycandidine A.

Solution combustion synthesis of high-entropy metal spinel oxide as oxygen evolution reaction catalyst

High-entropy metal spinel oxide (HEO) is proved to be a promising oxygen evolution reaction (OER) catalyst with high catalytic performance and stability. A short routine synthesis process based on solution combustion synthesis was proposed to prepare (Co0.25Ni0.25Mn0.25Zn0.25)Fe2O4 spinel HEO in this work. During the process, the products were rapidly synthesized and melted due to the high-temperature reaction, and then quickly crystallized on the surface of nickel foam to form a nano-structure coating. With the aid of nano-scale spinel structure, the overpotential of non-activation HEO electrode reaches 276 mV at the current density of 10 mA·cm−2, and after 100 h i-t test, it can be further reduced to 230 mV, which proves the high activity of OER catalysis. The promotion of OER catalytic performance can be attributed to the surface reconstruction caused by the selective element leaching and the boost of oxygen vacancy, leading to the formation of nano-scale flocculation around spinel core after the long-term OER process. This work indicates a special casting process for functional materials and explores the application of rapid crystallization.

Short Hydroacylation-Based Synthesis of Four Aryl-3-hydroxypropanones, Predictable Biomass-Derived C9 Platform Molecules

A two-step protocol for the synthesis of aryl-3-hydroxypropanones, which were regarded as lignin degradation products, was proposed herein. This protocol provided a more rapid and easier access to aryl-3-hydroxypropanones, and aryl-3-hydroxypropanones were expected to be ideal platform molecules for the synthesis of more complex value-added targets.

Squarephaneic Tetraanhydride: A Conjugated Square-Shaped Cyclophane for the Synthesis of Porous Organic Materials.

Aromatic carboxylic anhydrides are ubiquitous building blocks in organic materials chemistry and have received considerable attention in the synthesis of organic semiconductors, pigments, and battery electrode materials. Here we extend the family of aromatic carboxylic anhydrides with a unique new member, a conjugated cyclophane with four anhydride groups. The cyclophane is obtained in a three-step synthesis and can be functionalised efficiently, as shown by the conversion into tetraimides and an octacarboxylate. Crystal structures reveal the high degree of porosity achievable with the new building block. Excellent electrochemical properties and reversible reduction to the tetraanions are shown for the imides; NMR and EPR measurements confirm the global aromaticity of the dianions and evidence the global Baird aromaticity of the tetraanions. Considering the short synthesis and unique properties, we expect widespread use of the new building block in the development of organic materials.

Short Scalable Route to Apiaceae Sesquiterpene Scaffolds: Total Synthesis of 4-epi-Epiguaidiol A.

The oxy-Cope/ene reaction cascade to form a locked elemane conformer allows the short scalable synthesis of versatile Apiaceae scaffolds. The divergent fate of the obtained macrocyclic germacrane is surveyed under cationic and dioxygen-induced Prins-type reaction conditions to allow the diastereoselective synthesis of oxidized Apiaceae guaiane congeners and the total synthesis of 4-epi-epiguaidiol A. Additionally, the unprecedented reduction of a hydrogen-bond-biased guaiane substrate permits the chemoselective synthesis of desoxo-jungiaguaiane.

Facile Fabrication of α-Alumina Hollow Fiber-Supported ZIF-8 Membrane Module and Impurity Effects on Propylene Separation Performance.

The separation of C3 olefin and paraffin, which is essential for the production of propylene, can be facilitated by the ZIF-8 membrane. However, the commercial application of the membrane has not yet been achieved because the fabrication process does not meet industrial regulatory criteria. In this work, we provide a straightforward and cost-effective membrane fabrication technique that permits the rapid synthesis of ZIF-8 hollow fiber membranes. The scalability of the technology was confirmed by the incorporation of three ZIF-8 hollow fiber membranes into a single module using an introduced fiber mounting methodology. The molecular sieving characteristics of the ZIF-8 membrane module on a binary combination of C3 olefin and paraffin (C3H6/C3H8 selectivity of 110 and a C3H6 permeance of 13 GPU) were examined at atmospheric conditions. In addition, the high-pressure performance of these membranes was demonstrated at a 5 bar of equimolar binary feed pressure with a C3H6/C3H8 selectivity of 55 and a C3H6 permeance of 9 GPU due to propylene adsorption site saturation. To further accurately portray the separation performance of the membrane on an actual industrial feed, the effect of impurities (ethylene, ethane, butylene, i-butane, and n-butane), which can be found in C3 splitters, was investigated and a considerable decrement (~15%) in the propylene permeance upon an interaction with C4 hydrocarbons was confirmed. Finally, the long-term stability of the ZIF-8 membrane was confirmed by continuous operation for almost a month without any loss of its initial performance (C3H6/C3H8 separation factor of 110 and a C3H6 permeance of 13 GPU). From an industrial point of view, this straightforward technique could offer a number of merits such as a short synthesis time, minimal chemical requirements, and excellent reproductivity.

Short, Divergent, and Enantioselective Total Synthesis of Bioactive ent-Pimaranes.

We present the first total synthesis of eight ent-pimaranes via a short and enantioselective route (11-16 steps). Key features of the divergent synthesis are a Sharpless asymmetric dihydroxylation, a Brønsted acid catalyzed cationic bicyclization, and a mild Rh-catalyzed arene hydrogenation for rapid access to a late synthetic branching point. From there on, selective functional group manipulations enable the synthesis of ent-pimaranes bearing different modifications in the A- and C-rings.

3,3-Difluoroallyl Sulfonium Salts: Practical and Bench-Stable Reagents for Highly Regioselective gem-Difluoroallylations.

The site-selective introduction of the difluoromethylene group into organic molecules has important applications in producing pharmaceuticals and agrochemicals. However, the general and efficient methods that can construct both C(sp2 )-CF2 R and C(sp3 )-CF2 R bonds remain challenging. Here, we disclose a new type of practical and bench-stable difluoroalkylating reagent 3,3-difluoroallyl sulfonium salt (DFAS) that can be practically prepared from inexpensive and bulk chemical feedstock 3,3,3-trifluoropropene. This reagent allows highly regioselective gem-difluoroallylation of various organozinc reagents, including aryl, primary, secondary, and tertiary alkyl zinc reagents, via copper catalysis under mild reaction conditions with high efficiency. The reaction can also be extended to a series of substituted DFASs. Application of the approach leads to the short synthesis of complex analogs, showing the prospect of DFASs in medicinal chemistry.

3,3‐Difluoroallyl Sulfonium Salts: Practical and Bench‐Stable Reagents for Highly Regioselective gem ‐Difluoroallylations

The site-selective introduction of the difluoromethylene group into organic molecules has important applications in producing pharmaceuticals and agrochemicals. However, the general and efficient methods that can construct both C(sp2)-CF2R and C(sp3)-CF2R bonds remain challenging. Here, we disclose a new type of practical and bench-stable difluoroalkylating reagent 3,3-difluoroallyl sulfonium salt (DFAS) that can be practically prepared from inexpensive and bulk chemical feedstock 3,3,3-trifluoropropene. This reagent allows highly regioselective gem-difluoroallylation of various organozinc reagents, including aryl, primary, secondary, and tertiary alkyl zinc reagents, via copper catalysis under mild reaction conditions with high efficiency. The reaction can also be extended to a series of substituted DFASs. Application of the approach leads to the short synthesis of complex analogs, showing the prospect of DFASs in medicinal chemistry.