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Since early 2020, scientists have strived to find an effective solution to fight SARS-CoV-2, in particular by developing reliable vaccines that inhibit the spread of the disease and repurposing drugs for combatting its effects on the human body. The antiviral prodrug Remdesivir is still the most widely used therapeutic during the early stages of the infection. However, the current synthetic routes rely on the use of protecting groups, air-sensitive reagents, and cryogenic conditions, thus impeding a cost-efficient supply to patients. We have, therefore, focused on the development of a straightforward, direct addition of (hetero)arenes to unprotected sugars. Here we report a silylium-catalyzed and completely stereoselective C-glycosylation that initially yields the open-chain polyols, which can be selectively cyclized to provide either the kinetic α-furanose or the thermodynamically favored β-anomer. The method significantly expedites the synthesis of Remdesivir precursor GS-441524 after a subsequent Mn-catalyzed C-H oxidation and deoxycyanation., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Various tetrazole and oxadiazole C-nucleoside analogues were synthesized starting from pure α- or β-glycosyl-cyanide. The synthesis of glycosyl-cyanide as key precursor was optimized on gram-scale to furnish crystalline starting material for the assembly of C-nucleosides. Oxadizole C-nucleosides were synthesized via two independent routes. First,  the glycosyl-cyanide was converted into an amidoxime which upon ring closure offered an alternative pathway for the assembly of 1,2,4-oxadizoles in an efficient manner. Second, both anomers of glycosyl-cyanide were transformed into tetrazole nucleosides followed by acylative rearrangement to furnish 1,3,4-oxadiazoles in high yields. These protocols offer an easy access to otherwise difficult to synthesize C-nucleosides in good yield and protecting group compatibility. These C-nucleosides were evaluated for their antitumor activity. This work paves a path for facile assembly of library of new chemical entities useful for drug discovery., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The current portfolio of organoselenium compounds applicable as volatile precursors for atomic layer deposition can be denoted as very limited. Hence, we report herein facile and cost-effective preparation of two bis(trialkylstannyl)selenides as well as one selenole and three bis(trialkylsilyl)selenides. Their syntheses have been optimized to: (i) use readily available and inexpensive starting materials, (ii) involve operationally simple methodology (heating in a pressure vessel), (iii) use a minimum amount of additives and catalysts, and (iv) either exclude additional purification or involve only simple distillation. The chemical structure of prepared Se derivatives was confirmed by multinuclear NMR and GC/MS. Their fundamental thermal properties were investigated by differential scanning calorimetry (DSC) and TGA methods that revealed thermal stability within the range of 160-300 °C.

Stereoselective total synthesis of Patulolide C has been accomplished from easily available and inexpensive ( S ) - chiral epoxide. The key steps involved in the concise synthesis of Patulolide C utilizes ring opening of chiral epoxide, cleavage of 1,2-diol, deprotection of benzyl ether of hydroxyl acid and Yamaguchi macrolactonisation dilution conditions as key steps. The advantage of this method include inexpensive starting material, mild reaction conditions and high purity of products.

This article describes the gram-scale liquid-phase peptide synthesis of C-terminal-modified enkephalin analogues that possess high analgesic efficacy in animals, high potency for mu and delta opioid receptors, and high metabolic stability and potential blood-brain barrier permeability. Despite the long cycle time and tedious purification steps, liquid-phase synthesis is still a preferred method for large-scale peptide synthesis due to its cost effectiveness (i.e., amount of amino acids and reagents required), easy detection, and isolation of impurities compared with solid-phase synthesis. A robust liquid-phase synthesis protocol is described, involving BOP-assisted coupling and Boc deprotection, which has been well established in the laboratory and is a useful synthetic protocol for cost-effective production of peptide drugs. © 2019 by John Wiley & Sons, Inc., (© 2019 John Wiley & Sons, Inc.)

Antisense oligonucleotide (AO)-mediated splice modulation has been established as a therapeutic approach for tackling genetic diseases. Recently, Exondys51, a drug that aims to correct splicing defects in the dystrophin gene was approved by the US Food and Drug Administration (FDA) for the treatment of Duchenne muscular dystrophy (DMD). However, Exondys51 has relied on phosphorodiamidate morpholino oligomer (PMO) chemistry which poses challenges in the cost of production and compatibility with conventional oligonucleotide synthesis procedures. One approach to overcome this problem is to construct the AO with alternative nucleic acid chemistries using solid-phase oligonucleotide synthesis via standard phosphoramidite chemistry. 2'-Fluoro (2'-F) is a potent RNA analogue that possesses high RNA binding affinity and resistance to nuclease degradation with good safety profile, and an approved drug Macugen containing 2'-F-modified pyrimidines was approved for the treatment of age-related macular degeneration (AMD). In the present study, we investigated the scope of 2'-F nucleotides to construct mixmer and gapmer exon skipping AOs with either 2'-O-methyl (2'-OMe) or locked nucleic acid (LNA) nucleotides on a phosphorothioate (PS) backbone, and evaluated their efficacy in inducing exon-skipping in mdx mouse myotubes in vitro. Our results showed that all AOs containing 2'-F nucleotides induced efficient exon-23 skipping, with LNA/2'-F chimeras achieving better efficiency than the AOs without LNA modification. In addition, LNA/2'-F chimeric AOs demonstrated higher exonuclease stability and lower cytotoxicity than the 2'-OMe/2'-F chimeras. Overall, our findings certainly expand the scope of constructing 2'-F modified AOs in splice modulation by incorporating 2'-OMe and LNA modifications.

Amphiphilic aminoglycosides have attracted interest due to their novel antifungal activities. A crucial but often neglected factor for drug development in academia is cost of production. Herein is reported a one-step, inexpensive synthesis of amphiphilic alkyl kanamycins constituted with only natural components. The synthetic methodology also enabled the preparation of a series fluorescent amphiphilic aryl kanamycins for direct structure-activity mode of action studies. The lead compounds showed prominent antifungal activities against a panel of fungi, including Fusarium graminearum, Cryptococcus neoformans, and several Candida sp., and also significant antibacterial activities. With fluorescence-based whole cell assays, the aryl amphiphilic kanamycins were observed to permeabilize fungal surface membranes at faster rates than bacterial surface membranes. Also, the antifungal action of the amphiphilic kanamycins was observed to occur in a biphasic mode with an initial fast phase correlated with rapid membrane permeabilization at subminimal inhibitory concentrations and a slower phase membrane permeabilization that elevates the reactive oxygen species production leading to cell death. Inactive hydrophobic amphiphilic kanamycins displayed no membrane permeabilization. The results offer cost-effective methods for producing amphiphilic kanamycins and reveal insights into how nonfungal specific amphiphilic kanamycins can be employed for fungal specific diagnostic and therapeutic applications.

Quinolone 006 is under development as an anti-methicillin-resistant Staphylococcus aureus quinolone antibiotic. A linear synthetic route was utilized to prepare the compound on a multi-kilogram scale with an overall yield of 71%. The process was optimized by controlling the temperature and the vacuum pressure. Examples of parameters examined in an effort to control the polymorphism of the 006 active pharmaceutical ingredient are described.

A simple synthesis, which utilizes a thin film microfluidic reactor for a problematic step, of a potent inhibitor of α-N-acetylhexosaminidases, DGJNAc, has been developed., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Peptides represent a promising source of new medicines, but improved technologies are needed to facilitate discovery and optimization campaigns. In particular, longer peptides with multiple disulfide bridges are challenging to produce, and producing large numbers of structurally related variants is dissuasively costly and time-consuming. The principal cost and time drivers are the multiple column chromatography purification steps that are used during the multistep chemical synthesis procedure, which involves both ligation and oxidative refolding steps. In this study, we developed a method for multiplex parallel synthesis of complex peptide analogs in which the structurally variant region of the molecule is produced as a small peptide on a 384-well synthesizer with subsequent ligation to the longer, structurally invariant region and oxidative refolding carried out in-well without any column purification steps. To test the method, we used a panel of 96 analogs of the chemokine RANTES (regulated on activation normal T cell expressed and secreted)/CCL5 (69 residues, two disulfide bridges), which had been synthesized using standard approaches and characterized pharmacologically in an earlier study. Although, as expected, the multiplex method generated chemokine analogs of lower purity than those produced in the original study, it was nonetheless possible to closely match the pharmacological attributes (anti-HIV potency, capacity to elicit G protein signaling, and capacity to elicit intracellular receptor sequestration) of each chemokine analog to reference data from the earlier study. This rapid, low-cost approach has the potential to support discovery and optimization campaigns based on analogs of other chemokines as well as those of other complex peptide and small protein targets of a similar size., (© 2018 Paolini-Bertrand et al.)

The power of the Cloud has been harnessed for pharmaceutical compound production with remote servers based in Tokyo, Japan being left to autonomously find optimal synthesis conditions for three active pharmaceutical ingredients (APIs) in laboratories in Cambridge, UK. A researcher located in Los Angeles, USA controlled the entire process via an internet connection. The constituent synthetic steps for Tramadol, Lidocaine, and Bupropion were thus optimized with minimal intervention from operators within hours, yielding conditions satisfying customizable evaluation functions for all examples., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In this work, the three-dimensional nitrogen-doped nanostructured carbons with hierarchical architectures (3D-NNCsHAs) with high density of defective sites, high surface area and pluralities of pore size distributions was prepared through the pyrolysis of sea-tangle (Laminaria japonica), an inexpensive, eco-friendly and abundant precursor. Benefitting from their structural uniqueness, a selective and sensitive ascorbic acid (AA) sensor based on 3D-NNCsHAs was developed. Compared to the glassy carbon electrode (GCE) and the carbon nanotubes modified GCE (CNTs/GCE), the 3D-NNCsHAs modified GCE (3D-NNCsHAs/GCE) presents higher performance towards the electrocatalysis and detection of AA, such as lower detection limit (1 μM), wider linear range (10-4410 μM) and lower electrooxidation peak potential (-0.02 V vs. Ag/AgCl). In addition, 3D-NNCsHAs/GCE also exhibits high anti-interference and anti-fouling abilities for AA detection. Particularly, the fabricated 3D-NNCsHAs/GCE is able to determine AA in real samples and the results acquired are satisfactory. Therefore, the 3D-NNCsHAs can be considered as a kind of novel electrode nanomaterial for the fabrication of selective and sensitive AA sensor for the extensive practical applications ranging from food analysis, to pharmaceutical industry and clinical test., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In materials science and engineering, the designing of hydrogels with excellent self-healing and tunable mechanical properties is an inviting issue. In this study, we introduce the sacrificial bonds interactions in a hybrid hydrogel of natural and synthetic polymers, to give a hydrogel with autonomous self-healing ability and tunable mechanical properties. Glycogen, a natural polymer tends to strengthen the hydrogel while PVA, a synthetic polymer plays a critical role in the flexibility and stretchability of the hydrogel. Hydrogels were designed by the sacrificial non-covalent interactions with physical cross-linking of the polymer chains to the trivalent metal ions. Functional groups of the polymers interact with sacrificial hydrogen bonds with and with the metal ions, they interact through sacrificial coordination interactions with different strength, results tunable sacrificial bonds. Weaker sacrificial bonds rupture prior to the strong sacrificial bonds upon external loading, which dissipate the energy and endow the hydrogel with adjustable mechanical and self-healing properties. The tunable mechanical properties and excellent self-healing efficiency enlarge the application areas of the developed hydrogel in various fields., (Copyright © 2018. Published by Elsevier B.V.)

The scarcity of precious metals has led to the development of sustainable strategies for metal-catalyzed cross-coupling reactions. The establishment of new catalytic methods using iron is attractive owing to the low cost, abundance, ready availability, and very low toxicity of iron. In the last few years, sustainable methods for iron-catalyzed cross-couplings have entered the critical area of pharmaceutical research. Most notably, iron is one of the very few metals that have been successfully field-tested as highly effective base-metal catalysts in practical, kilogram-scale industrial cross-couplings. In this Minireview, we critically discuss the strategic benefits of using iron catalysts as green and sustainable alternatives to precious metals in cross-coupling applications for the synthesis of pharmaceuticals. The Minireview provides an essential introduction to the fundamental aspects of practical iron catalysis, highlights areas for improvement, and identifies new fields to be explored., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Peptide macrocycles are widely utilized in the development of high affinity ligands, including stapled α-helices. The linear rigidity of a 1,3-diynyl linkage provides an optimal distance (7 Å) between β-carbons of the i,i+4 amino acid side chains, thus suggesting its utility in stabilizing α-helical structures. Here, we report the development of an on-resin strategy for an intramolecular Glaser reaction between two alkyne-terminated side chains by using copper chloride, an essential bpy-diol ligand, and diisopropylethylamine at room temperature. The efficiency of this ligation was illustrated by the synthesis of (i,i+4)-, (i,i+5)-, (i,i+6)-, and (i,i+7)-stapled BCL-9 α-helical peptides using the unnatural amino acid propargyl serine. Overall, this procedurally simple method relies on inexpensive and widely available reagents to generate low molecular weight 23-, 26-, 29-, and 32-membered peptide macrocycles., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Enantioselective Pd-catalyzed allylic alkylations of dihydropyrido[1,2-a]indolone (DHPI) substrates were used to construct the C20-quaternary stereocenters of multiple monoterpene indole alkaloids. Stereodivergent Pictet-Spengler and Bischler-Napieralski cyclization/reduction cascades furnish the cis- and trans-fused azadecalin subunits present in Aspidosperma and Kopsia alkaloids, respectively, en route to highly efficient syntheses of (+)-limaspermidine and (+)-kopsihainanine A., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Hippolachnin A (1) is an antifungal polyketide that bristles with ethyl groups mounted onto a caged heterotricyclic core. It has shown potent activity against Cryptococcus neoformans, a yeast that can affect immunocompromised patients as an opportunistic pathogen. Herein we describe a concise, diversifiable, and scalable synthesis of (±)-hippolachnin A (1). It features a powerful photochemical opening step, a diastereoselective addition of an ethyl cuprate and an unusual strategy to install two additional ethyl groups that makes use of a thiocarbonyl ylide generated in situ.

Wogonin and astringin were synthesized from inexpensive chrysin and piceid in short steps. The key feature of these syntheses is site-selective transformation. The target molecules were obtained in 27 and 62% yields from the starting materials, respectively.

Physiochemical disintegration of waste activated biosolids (WAB) through thermochemical (TC) pretreatment requires high energy and cost for efficient energy generation. Therefore in the present study, an attempt has been made to enhance the biodegrdability and to minimize the operational cost of TC pretreatment by combining it with ozonation. A higher solubilization of about 30.4% was achieved at lesser energy input of about 141.02kJ/kgTS and a ozone dosage of about 0.0012mgO 3 /mgSS through this combined thermo chemo ozone (TCO 3 ) pretreatment. The methane production potential (0.32gCOD/gCOD) of TCO 3 pretreatment was comparatively higher than the (0.19gCOD/gCOD) TC pretreatment. The energetic analysis and economic assessment of the proposed method of pretreatment can possibly reduces the energy requirement of TC pretreatment with a positive net profit of about 35.49$/ton of biosolids., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Two series of diaza derivatives were prepared by solvent-free condensation of benzoic acid and 4-substituted phenylhydrazines in order to obtain phenylhydrazides (HYD series) and, by oxidation of these compounds, the corresponding benzoyldiazenes (DIA series). Both sets were evaluated as inhibitors of soybean 15-lipoxygenase activity and antioxidant capability in the FRAP and CUPRAC assays. The most potent inhibitors of both series exhibited IC 50 values in the low micromolar range. Kinetic studies showed that at least the more active compounds were competitive inhibitors. Docking results indicated that the most potent inhibitor interacts strongly with Ile-839 and iron in the active site., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

To obtain key sugar derivatives for making homooligomeric foldamers or α/β-chimera peptides, economic and multigram scale synthetic methods were to be developed. Though described in the literature, the cost-effective making of both 3-amino-3-deoxy-ribofuranuronic acid (H-t X-OH) and its C-3 epimeric stereoisomer, the 3-amino-3-deoxy-xylofuranuronic acid (H-c X-OH) from D-glucose is described here. The present synthetic route elaborated is (1) appropriate for large-scale synthesis; (2) reagent costs reduced (e.g. by a factor of 400); (3) yields optimized are ~80% or higher for all six consecutive steps concluding -t X- or -c X- and (4) reaction times shortened. Thus, a new synthetic route step-by-step optimized for yield, cost, time and purification is given both for D-xylo and D-ribo-amino-furanuronic acids using sustainable chemistry (e.g. less chromatography with organic solvents; using continuous-flow reactor). Our study encompasses necessary building blocks (e.g. -X-OMe, -X-O i Pr, -X-NHMe, Fmoc-X-OH) and key coupling reactions making -Aaa-t X-Aaa- or -Aaa-t X-t X-Aaa- type "inserts". Completed for both stereoisomers of X, including the newly synthesized Fmoc-c X-OH, producing longer oligomers for drug design and discovery is more of a reality than a wish.

We report star polymer metal-organic cage (polyMOC) materials whose structures, mechanical properties, functionalities, and dynamics can all be precisely tailored through a simple three-component assembly strategy. The star polyMOC network is composed of tetra-arm star polymers functionalized with ligands on the chain ends, small molecule ligands, and palladium ions; polyMOCs are formed via metal-ligand coordination and thermal annealing. The ratio of small molecule ligands to polymer-bound ligands determines the connectivity of the MOC junctions and the network structure. The use of large M 12 L 24 MOCs enables great flexibility in tuning this ratio, which provides access to a rich spectrum of material properties including tunable moduli and relaxation dynamics., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We describe a simple flow chemistry approach to libraries of ethyl 3-oxo-2-(substituted-phenylamino)-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carboxylates (12a-l) and N-ethyl-3-oxo-2-(substituted-phenylamino)-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carboxamides (13a-l) in 38-87% yields. This scaffold is poorly described in the chemical literature. Screening against a panel of 11 cancer and one normal cell line showed that the amide linked library 13a-l was devoid of toxicity. Whereas the ester linked analogues 12b, 12c, 12g, 12j and 12l were highly cytotoxic with growth inhibition (GI 50 ) values from 0.34 to >50 μM across all cell lines, with the 2-OH-Ph substituted 12l analogue presenting with sub-micromolar potency against the A2780 (ovarian; 0.34 ± 0.04 μM), BEC-2 (glioblastoma; 0.35 ± 0.06 μM), MIA (pancreas; 0.91 ± 0.054 μM) and SMA (murine glioblastoma; 0.77 ± 0.029 μM) carcinoma cell lines. Interestingly, the U87 glioblastoma cell line showed inherent resistance to growth inhibition by all analogues (GI 50 32 to >50 μM) while the A2780 cells were highly sensitive (GI 50 3.8-0.34 μM), suggesting that the analogues developed herein may be valuable lead compounds for the development of ovarian carcinoma specific cytotoxic agents. The differences in amide versus ester cytotoxicity was consitent with esterase cleaveage to release the cytotoxic warhead.

Iodonium compounds play a pivotal role in (18) F-fluorination of radiopharmaceuticals containing non-activated arenes. However, preparation of these species is limited to oxidation conditions or exchange with organometallics that are prepared from aryl halides. Herein we describe a novel "one-pot" process to assemble aryl(isoquinoline)iodonium salts in 40-94 % yields from mesoionic carbene silver complex and Aryl-I-Py2 (OTf)2 . The method is general, practical, and compatible with well-functionalized molecules as well as useful for the preparation of a wide range of (18) F-labeled isoquinolines resulting in up to 92 % radiochemical conversion. As proof of concept, a fluorinated isoquinoline alkaloid, (18) F-aspergillitine is prepared in 10 % isolated radiochemical yield from the corresponding phenyl(aspergillitine)iodonium salt., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Indandione is an important starting material that has drawn great attention in various organic transformations because of its attributes, such as low cost, easy to handle and eco-friendliness generally affording the corresponding products in excellent yields. In this review, we summarize recent data describing the most important MCRs reactions in which one of the starting materials is indandione. This review will also present two-, three-, four-, and five-component and one-pot reactions for the functionalization of indandione with the to increase awareness on the versatility of using this compound among organic chemists.

Studies of rare ketoses have been hampered by a lack of efficient preparation methods. A convenient, efficient, and cost-effective platform for the facile synthesis of ketoses is described. This method enables the preparation of difficult-to-access ketopentoses and ketohexoses from common and inexpensive starting materials with high yield and purity and without the need for a tedious isomer separation step., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Thin film flow chemistry using a vortex fluidic device (VFD) is effective in the scalable acylation of amines under shear, with the yields of the amides dramatically enhanced relative to traditional batch techniques. The optimized monophasic flow conditions are effective in ≤80 seconds at room temperature, enabling access to structurally diverse amides, functionalized amino acids and substituted ureas on multigram scales. Amide synthesis under flow was also extended to a total synthesis of local anesthetic lidocaine, with sequential reactions carried out in two serially linked VFD units. The synthesis could also be executed in a single VFD, in which the tandem reactions involve reagent delivery at different positions along the rapidly rotating tube with in situ solvent replacement, as a molecular assembly line process. This further highlights the versatility of the VFD in organic synthesis, as does the finding of a remarkably efficient debenzylation of p-methoxybenzyl amines., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A truly cost-effective strategy for the synthesis of amine-tethered porous polymer networks (PPNs) has been developed. A network containing diethylenetriamine (PPN-125-DETA) exhibits a high working capacity comparable to current state-of-art technology (30 % monoethanolamine solutions), yet it requires only one third as much energy for regeneration. It has also been demonstrated to retain over 90 % capacity after 50 adsorption-desorption cycles of CO2 in a temperature-swing adsorption process. The results suggest that PPN-125-DETA is a very promising new material for carbon capture from flue gas streams., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Nature has evolved to produce unique and diverse natural products that possess high target affinity and specificity. Natural products have been the richest sources for novel modulators of biomolecular function. Since the chemical synthesis of urea by Wöhler, organic chemists have been intrigued by natural products, leading to the evolution of the field of natural product synthesis over the past two centuries. Natural product synthesis has enabled natural products to play an essential role in drug discovery and chemical biology. With the introduction of novel, innovative concepts and strategies for synthetic efficiency, natural product synthesis in the 21st century is well poised to address the challenges and complexities faced by natural product chemistry and will remain essential to progress in biomedical sciences., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In this account, we have highlighted our most recent works towards the total synthesis of bioactive natural products, which have resulted in the development of several novel synthetic methods. Inspired and guided by strategies based on diversity-oriented synthesis, we have successfully applied the novel synthetic methodologies developed in our lab to the total synthesis of a diverse collection of structurally challenging targets. We have also documented the evolution of these synthetic strategies. The total syntheses described in this account have been organized from the perspective of different molecules whilst still alluding to the parallel synthetic strategies involved., (Copyright © 2014 The Chemical Society of Japan and Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Terpenoids constitute a significant fraction of molecules produced by living organisms that have found use in medicine and other industries. Problems associated with their procurement and adaptation for human use can be solved using chemical synthesis, which is an increasingly economical option in the modern era of chemistry. This article documents, by way of individual case studies, strategies for reducing the time and cost of terpene synthesis for drug discovery. A major trend evident in recent syntheses is that complex terpenes are increasingly realistic starting points for both medicinal chemistry campaigns and large-scale syntheses, at least in the context of the academic laboratory, and this trend will likely penetrate the commercial sector in the near future.

Here, we report the most inexpensive procedure for chemical synthesis of enantiomerically pure phenylalanine. As a source of chirality, we use the ultimately inexpensive chiral auxiliary, 1-(phenyl)ethylamine, incorporated into the specially designed ligands which form the corresponding intermediate Ni(II) complexes with racemic phenylalanine. Diastereomerically pure Ni(II) complexes, containing either (S)- or (R)-phenylalanine, were disassembled to produce enantiomerically pure target amino acid, along with recycling the chiral ligand. All reactions were conducted under operationally convenient conditions, featuring high yields and thus underscoring attractive cost structure of this method.

A straightforward strategy has been used to construct large BN-embedded π-systems simply from azaacenes. BN heterosuperbenzene derivatives, the largest BN heteroaromatics to date, have been synthesized in three steps. The molecules exhibit curved π-surfaces, showing two different conformations which are self-organized into a sandwich structure and further packed into a π-stacking column. The assembled microribbons exhibit good charge transport properties and photoconductivity, representing an important step toward the optoelectronic applications of BN-embedded aromatics.

Maleic anhydride esterified starch was synthesized by a dry method using corn starch as the material and maleic anhydride as the esterifying agent. The esterified starch (ES) was analyzed by Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS), which confirmed that there was a successful esterification reaction between the maleic anhydride and corn starch. The effects of reaction temperature and time on the degree of substitution of esterified starch were studied, where the results showed that 80 °C of reaction temperature and 3h of reaction time were optimal conditions. The result of XPS testing demonstrated that the esterification reaction led to increase of ester bonds in starch. The scanning electron microscopy (SEM) and laser particle size analyzer results showed that esterification led to roughness on the surface of the starch particle, and the particle size and distribution rate of esterification starch became larger. X-ray diffraction (XRD) analysis demonstrated that esterification reaction did not change the crystalline type of native starch. The differential scanning calorimeter (DSC) and thermo gravimetric analysis (TGA) confirmed that destruction of the crystal structure resulted in improved thermoplasticity of the starch, decreased the gelatinization temperature and increased the thermogravimetric rate of esterification starch., (Copyright © 2013 Elsevier B.V. All rights reserved.)

An efficient one-pot syntheses of aryl-3,3'-bis(indolyl)methanes (BIMs) from indole/2-methylindole and formylphenoxyaliphatic acid(s) is described. Esterification of carboxylic acid and aromatic electrophilic substitution reactions are achieved simultaneous in the presence of potash alum as a catalyst. This catalyst could be recovered and reused without substantial loss in its catalytic activity and the methodology could be applied on a range of closely related substrates. The solvation characteristics in ground and excited states of the compounds by monitoring the absorbance and fluorescence band maxima have been studied. The fluorescence studies in protic and aprotic solvents were rationalized on the basis of solute-solvent interaction and substituents effect on these photophysical processes analyzed. The compounds prepared showed efficient antimicrobial effect against human pathogens, cytotoxicity against A431 cell line, and DPPH radical scavenging effect. Single crystal XRD studies have been carried out for a few compounds synthesized in this work., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Ambient ionization techniques allow complex chemical samples to be analyzed in their native state with minimal sample preparation. This brings the obvious advantages of simplicity, speed, and versatility to mass spectrometry: Desorption electrospray ionization (DESI), for example, is used in chemical imaging for tumor margin diagnosis. This review on the extractive methods of ambient ionization focuses on chemical aspects, mechanistic considerations, and the accelerated chemical reactions occurring in charged liquid droplets generated in the spray process. DESI uses high-velocity solvent droplets to extract analytes from surfaces. Nano-DESI employs liquid microjunctions for analyte dissolution, whereas paper-spray ionization uses DC potentials applied to wet porous material such as paper or biological tissue to field emit charged analyte-containing solvent droplets. These methods also operate in a reactive mode in which added reagents allow derivatization during ionization. The accelerated reaction rates seen in charged microdroplets are useful in small-scale rapid chemical synthesis.

Prostaglandins are hormone-like chemical messengers that regulate a broad range of physiological activities, including blood circulation, digestion and reproduction. Their biological activities and their complex molecular architectures have made prostaglandins popular targets for synthetic organic chemists for over 40 years. Prostaglandin analogues are widely used as pharmaceuticals and some, such as latanoprost, which is used to treat glaucoma, have become billion-dollar drugs. Previously reported syntheses of these compounds are quite lengthy, and every chemical step costs time and energy, generates waste and is accompanied by material losses. Using a new bond disconnection, here we report a concise synthesis of the most complex prostaglandin, PGF2α, with high levels of control of relative and absolute stereochemistry, and fewer steps. The key step is an aldol cascade reaction of succinaldehyde using proline organocatalysis to create a bicyclic enal in one step and an enantiomeric excess of 98%. This intermediate bicyclic enal is fully primed with the appropriate functionality for attachment of the remaining groups. Access to this bicyclic enal will not only render existing prostaglandin-based drugs more affordable, but will also facilitate the rapid exploration of related chemical structures around the ubiquitous five-membered ring motif, such as potentially therapeutic prostaglandin analogues.

An efficient and organo-catalyzed method has been developed for the synthesis of 5-arylidenethiazolidine-2,4-diones and 5-arylidene-2-thioxothiazolidin-4-ones via Knoevenagel condensation of arylaldehydes 1 and 2,4-thiazolidinedione 2a/2-thioxothiazolidin-4-one 2b under mild conditions. Urea-adduct 4 and azomethine 5 also afford arylidene-products 3 by reacting with 2a-b via addition-elimination reaction. This protocol has the features of use of inexpensive, ecofriendly readily available, effective catalyst system viz. urea/thiourea, avoidance of volatile solvents, excellent yield and simple work-up procedure., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

A concise synthesis of polycyclic pyrroloindolines from simple malonic diamides via an intramolecular oxidative coupling/condensative cyclization cascade process is reported. The reaction provides an efficient method to construct polycyclic pyrroloindolines in good to excellent yields, which should be useful in the synthesis of natural products and pharmaceutical molecules.

A unique photochemical flow reactor featuring quartz tubing, an aluminum mirror and temperature control has been developed for the photo-induced electron-transfer deoxygenation reaction to produce 2'-deoxy and 2',3'-dideoxynucleosides. The continuous flow format significantly increased the efficiency and selectivity of the reaction.

A simple and efficient three components domino reaction of γ-butyrolactam (2-pyrrolidinone), aromatic aldehyde and substituted thiophenol catalyzed by elemental iodine resulted in the formation of 1-((phenylthio)(phenyl)methyl)pyrrolidin-2-one derivatives. The stability of the synthesized analogues was evaluated in stimulated gastric fluid (SGF) and bovine serum albumin (BSA). In vitro anticancer activity was investigated in the low micromolar range and a few analogues were found to possess good activity. This current protocol provides several advantages like shorter reaction time, excellent yield and convenient work-up.

A straightforward and efficient method for the palladium-catalyzed direct cross-coupling of chromones with various quinones has been developed to rapidly construct isoflavone quinone structural motifs.

Here we present new routes for the efficient syntheses of 6,5'-(S)- and 6,5'-(R)-cyclouridine. The syntheses utilize readily accessible uridine as a starting material. This route to the R diastereomer is significantly more efficient than previous synthetic efforts, allowing us to obtain large amounts of pure material for future biological testing.

The first total synthesis of the hybrid ganglioside X2, which consisted of a highly branched octasaccharide and ceramide moieties, was accomplished by using a glucosyl ceramide cassette approach. With a disaccharyl donor, the heptasaccharide could not be constructed by glycosylation of the C4 hydroxy group of galactose at the reducing end of the pentasaccharide. In contrast, through an alternative approach with two branched glycan units, a GM2-core trisaccharide, and a lacto-ganglio tetrasaccharide, the heptasaccharyl donor could be prepared and subsequently joined with a glucosyl ceramide cassette to afford the protected ganglioside, X2. Finally, global deprotection completed the synthesis, thus affording the pure ganglioside X2., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Designer drugs include, among others, synthetic cannabinoids and synthetic cathinones. These new "legal highs" drugs are sold on line for recreational public or private use. Synthetic cannabinoids are a psychoactive herbal and chemical product that, when used, mimics the effects of cannabis. Cathinone is a naturally occurring betaketone amphetamine analogue found in the leaves of the Catha edulis plant. Synthetic cathinones are phenylalkylamines derivatives, and may possess both amphetamine-like properties. They are often sold as "bath salts" or "plant food" and labeled "not for human consumption" to circumvent drug abuse legislation. The absence of legal risks, the ease of obtaining these drugs, the moderate cost, and the avaibility via Internet are the main criteria attracting the user. There is evidence that negative health and social consequences may occur in recreational and chronic users. The addictive potential of designer drugs is not weak. Furthermore, there is a lack of epidemiological, pharmacological, animal, clinical, psychological and therapeutic data concerning these new synthetic agents.

A mild and efficient synthesis of 1-aryl-1-fluoroethenes from benzothiazolyl (aryl)fluoromethyl sulfones and paraformaldehyde, under DBU- or Cs(2)CO(3)-mediated conditions at room temperature, is described. A comparable diethyl fluoro(naphthalen-2-yl)methylphosphonate reagent does not react with paraformaldehyde under these mild conditions. The utility of the methodology for synthesis of terminal α-fluoroalkenes bearing electron-withdrawing functionalities is also shown., (This journal is © The Royal Society of Chemistry 2012)