Glycals have been extensively utilized as a versatile building block in the constructions of C-glycosides, branched sugars, and the total synthesis of natural products and biologically potent molecules. The versatility of glycals can be attributed to their easy availability and the presence of endocyclic ring oxygen in conjugation with the double bond. The inbuilt chirality further enhances its applicability in the chiral pool synthesis of natural products and pharmaceuticals. In this review, we have summarized the development made in the total synthesis of natural products and some medicinally relevant molecules from glycals.

1,2-Annulated pyranose sugars fused with six membered rings have emerged as an important class of carbohydrates with wide biological and synthetic utility. We now describe zinc chloride catalyzed one pot diastereoselective synthesis of sugar fused dioxazinanes from 1,2-anhydro sugars and N-substituted aromatic nitrones. Various aromatic nitrones with different substituents undergo the reaction smoothly. The developed strategy works well with both ester and ether protection on the sugar and proceeds under mild reaction conditions. The mechanism seems to involve activation of the anhydrosugar by ZnCl2 for nucleophilic attack by the nitrone followed by cyclization.

Correction for 'Diastereoselective synthesis of glycopyrans 1,2-annulated with dioxazinanes from 1,2-anhydrosugars and N-substituted nitrones' by Ajaz Ahmed et al., Org. Biomol. Chem., 2022, 20, 1436-1443, DOI: 10.1039/d1ob02310a.

Correction for 'Diastereoselective synthesis of glycopyrans 1,2-annulated with dioxazinanes from 1,2-anhydrosugars and N-substituted nitrones' by Ajaz Ahmed et al., Org. Biomol. Chem., 2022, 20, 1436-1443, DOI: 10.1039/d1ob02310a.

Synthesis of orthogonally protected 2‐silyl nucleosides were achieved by trans opening of sugar epoxides with nucleobases catalyzed by trimethylsilyltrifluoromethanesulfonate using hexamethyldisilazane both as solvent and silylating agent. Both α and β nucleosides were obtained with complete stereocontrol only by changing the epoxide stereochemistry. The synthesized nucleosides exist in different chair conformations depending upon the nature of protecting groups present in the sugar moiety as determined from coupling constants in the proton NMR. All the synthesized nucleosides were screened for biofilm inhibition activity against four bacterial pathogens and compound 7c was found to be most potent against Salmonella typhimurium with 1.22 µm biofilm inhibitory activity taking ciprofloxacin as control.

Triflic acid catalyzed cascade stereoselective reaction of glycals with styrenes delivers complex oxabicyclic scaffolds such as cis-oxadecalins or cis-cyclopentanofurans simply by tweaking the solvent. In the presence of participating solvents like benzene/toluene, cascade Ferrier C-glycosylation and double Friedel-Crafts reaction leads to densely chiral benzo-fused oxadecalins, whereas in DCM, an unprecedented ring-opening, ring-closing sequence generated cis-cyclopentanofurans. An attempt has been made to explain the above cascade sequences via intermediate trapping, kinetic experiments, and Baldwin's rules.

The reaction of glycals containing good leaving groups with aromatic vinyl azides to give α- C-glycosyl amides in good yields is described. Various vinyl azides with different groups undergo the reaction smoothly. In these reactions, an iminodiazonium intermediate is generated by the attack of the vinyl azide onto the glycal under Lewis acid conditions. This undergoes Schmidt-type denitrogenative 1,2-migration to form a nitrilium ion, which, upon hydrolysis, gives the desired C-glycosyl amide.

Induction of premature senescence represents a novel functional strategy to curb the uncontrolled proliferation of malignant cancer cells. This study unveils the regiospecific synthesis of novel isoxazoline derivatives condensed to ring A of medicinal plant product Withaferin-A. Intriguingly, the cis fused products with β-oriented hydrogen exhibited excellent cytotoxic activities against proliferating human breast cancer MCF7 and colorectal cancer HCT-116 cells. The most potent derivative W-2b triggered premature senescence along with increase in senescence-associated β-galactosidase activity, G2/M cell cycle arrest, and induction of senescence-specific marker p21Waf1/Cip1 at its sub-toxic concentration. W-2b conferred a robust increase in phosphorylation of mammalian checkpoint kinase-2 (Chk2) in cancer cells in a dose-dependent manner. Silencing of endogenous Chk2 by siRNA divulged that the amplification of p21 expression and senescence by W-2b was Chk2-dependent. Chk2 activation (either by ectopic overexpression or through treatment with W-2b) suppressed NM23-H1 signaling axis involved in cancer cell proliferation. Finally, W-2b showed excellent in vivo efficacy with 83.8% inhibition of tumor growth at a dose of 25 mg/kg, b.w. in mouse mammary carcinoma model. Our study claims that W-2b could be a potential candidate to limit aberrant cellular proliferation rendering promising improvement in the treatment regime in cancer patients.

Pd-catalyzed regio- and stereoselective C-nucleoside synthesis from pyranoid glycals and unactivated N,N-dialkyluracils is described. Depending upon the reaction conditions, either β-hydride or β-heteroatom eliminated C-nucleosides were obtained exclusively. Different glycals with various protecting groups reacted smoothly. Mechanistically, uracil first undergoes electrophilic palladation regioselectively at the C-5 position to generate the active organopalladium species, which then attacks the glycal in a regio- and stereoselective mode to generate C-nucleosides. The method obviates the use of heavy metals such as mercury or preactivation of protected uracils, making it an attractive strategy for C-nucleoside synthesis.

Tuberculosis continues to be the most dangerous infectious disease globally and need for development of new therapies is of utmost importance. In this study we describe the rationale design for synthesis using molecular hybridization and subsequent in-vitro antimycobacterial activity of various indolo-pyridone hybrid molecules against Mycobacterium tuberculosis H37Rv. A total of 16 indolo-pyridone hybrid molecules were synthesized with 85-90% yields and characterized by various spectroscopic techniques. Four compounds were ineffective with MIC > 256 mu g/ml (highest concentration tested), six exhibited poor activity with MIC > 100 mu g/ml, four showed moderate activity with MIC > 50 mu g/ml and two had notable anti-TB activity with MIC values 32 mu g/ml. Interestingly the last two compounds were observed equally effective against drug susceptible and various drug resistant strains including multidrug-resistant (MDR) strains, thereby clearly demonstrating their potential against MDR-TB. Our results showed that un-substituted aryl rings posses better antituberculosis activity than those having any kind of substitution and derivatives with small sized electron withdrawing groups in aryl ring exhibited activity while bigger groups lead to considerable loss in activity. The results of this study open up a new door for further SAR guided synthesis on one hand and on the other hand provide a promising opportunity that may lead to the discovery of a new class of antituberculosis agents.

Ethno-pharmacological relevance: The underground parts of Aquilegia fragrans are traditionally used for the treatment of wounds and various inflammatory diseases like bovine mastitis. However, there are no reports on the phytochemical characterization and antibacterial studies of A. fragrans.Aim of the study: To isolate compounds from the methanol extract of the underground parts of A. fragrans and determine their antibacterial activity against the pathogens of bovine mastitis. The study was undertaken in order to scientifically validate the traditional use of A. fragrans.Materials and methods: Five compounds were isolated from the methanol extract of the underground parts of A. fragrans using silica gel column chromatography. Structural elucidation of the isolated compounds was done using spectral data analysis and comparison with literature. High performance liquid chromatography (HPLC) was used for the qualitative and quantitative determination of isolated compounds in the crude methanol extract. The methanol extract and isolated compounds were evaluated for antibacterial activities against mastitis pathogens using broth micro-dilution technique.Results: The five isolated compounds were identified as (1) 2, 4-dihydroxyphenylacetic acid methyl ester (2) p-sitosterol (3) Aquilegiolide (4) Glochidionolactone-A and (5) Magnoflorine. A quick and sensitive HPLC method was developed for the first time for qualitative and quantitative determination of four isolated marker compounds from A. fragrans. The crude methanol extract and compound 5 exhibited weak antibacterial activities that varied between the bacterial species (MIC=500-3000 mu g/ml).Conclusions: The above results show that the crude methanol extract and isolated compounds from A. fragrans exhibit weak antibacterial activities. Further phytochemical and pharmacological studies are required for proper scientific validation of the folk use of this plant species in the treatment of various inflammatory diseases like bovine mastitis. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

Sugar enol ethers undergo efficient coupling at C-2 with unactivated cycloalkenes under a low Pd loading affording allylic substitution products. High diastereoselectivity was observed at the allylic centre with sterically hindered substrates. Generation of a π-allyl complex by the Pd(ii) catalyst via cleavage of the allylic C-H bond of the cycloalkene may be responsible for the formation of sp2-sp3 coupling products.

Reaction of peroxides with glycals, when carried in the presence of NIS affords2-deoxy-2-iodo-a-glycosides in good yields with predominant trans-diaxial selectivity at rt. Under photolytic conditions in the presence of catalytic eosin Y, the reaction leads to 2-deoxyglycosides or 2,3-unsaturated-a-glycosides.NIS plays two roles firstly, to form an iodonium ion with the glycal and secondly to bring about the decomposition of the organic peroxide into an alcohol that reacts with the activated sugar whereas blue LED light and Eosin Y bring about a radical-mediated glycosylation to give the a-2-deoxy glycoside or 2,3-unsaturated glycosides based on the protecting group at C-3 position of glycals.

Palladium catalysed ligand free highly regio- and chemoselective dehydrogenative C-3 alkenylation of pyrones and unprotected pyridones from unactivated alkenes is reported. Simple reaction conditions and broad substrate scope make the process useful.

Statement of problem. The utility of evidence-based clinical prosthetic dental decision making is, in part, predicated on the availability of high-quality clinical trials and the use of current best evidence. With literature or outcomes continually evolving, it is difficult to know how much information is available, how fast it changes, or where it is located.Purpose. This study identified and quantified the availability of high-quality prosthetic dental clinical trials, determined the dynamics of literature increase, and identified the location of relevant literature published within a specific decade.Material and methods. A search strategy based on the Medical Subject Headings (MeSH) vocabulary for prosthetic dentistry was developed to examine MEDLINE with use of the Ovid Web Gateway search engine between the years 1990-1999. Specific and sensitive methodologic search filters identified 4 categories of information: etiology, diagnosis, therapy, and prognosis. The identified studies were limited to human subjects and to articles written in English. The results were subdivided by year to identify trends and location of the literature. This evaluation did not include the following: (1) other databases or languages or (2) an evaluation of the validity or clinical applicability of the literature. The first factor would increase the estimated number of relevant articles, whereas the second factor would decrease it.Results. Between 1990 and 1999, MEDLINE identified 10,258 articles published in English on human prosthodontic issues. When subdivided by clinical category, the number of articles per year (mean +/- SD) for specific and sensitive searches, respectively, was as follows: etiology, 10 +/- 6 and 95 +/- 27; diagnosis, 11 +/- 5 and 77 +/- 21; therapy, 6 +/- 2 and 153 +/- 52; and prognosis, 13 +/- 6 and 91 +/- 27. For sensitive searches, this amounted to approximately 416 articles per year. The time-course analysis indicated that the number of articles in each category increased by approximately 7% per year. The articles were published in more than 60 different journals: approximately 50% of the articles were published in 14 journals, whereas the remaining articles were published in 46 journals.Conclusion. There appears to be substantial clinical prosthetic dental literature upon which to base clinical decisions. With the sensitive search strategy used as an estimate, to stay current, one would need to read and absorb approximately 8 articles per week, 52 weeks per year, across 60 different journals. Increases in the volume of literature each year make access even more difficult. These trends suggest the need for computer-based clinical knowledge systems.

Statement of problem. Immediate loading of implants may be a predictable treatment alternative when cross-arch stabilization with a fixed provisional is observed. Purpose. This study investigated the effect of immediate masticatory loading on the stability of single-standing dental implants with 4 different surfaces. Material and methods. A total of 40 solid screw implants (diameter 3.3 mm, length 8 mm) were placed in the mandibles of 4 beagle dogs. Test groups included 3 hydroxyapatite (HA) coatings of titanium plasma-sprayed (TPS) implants. Implants with TPS alone served as control. Gold crowns were inserted 2 days after implant placement and the dogs were immediately put on a hard food diet. Implants were followed for 6 months after loading. Clinical and radiographic assessments of implants were performed at time of crown insertion (baseline) and after 1, 3, and 6 months of loading. The Periotest instrument was used for mobility measurements and radiographs were obtained for evaluation of peri-implant radiolucency and measurement of crestal bone changes. Results. Of 40 implants, 39 displayed no discernible mobility, corresponding to successful clinical function. Peri-implant radiolucencies were absent for all but the 1 mobile implant. The reduction in crestal bone levels adjacent to the implants between baseline and 6 months was statistically significant (P <.0001). No statistically significant differences in crestal bone level changes over time were found between the various coatings demonstrating the absence of a treatment effect initiated by the surface coatings. Conclusion. In this study in beagle dogs, immediate masticatory loading of single-standing dental implants did not jeopardize tissue integration, provided the implants had excellent primary stability. (J Prosthet Dent 1999;82:428-35.)

Evidence-based clinical practice integrates the best available evidence with clinical expertise. This article presents a clinical case scenario and, using a four-step, evidence-based approach, demonstrates how to (1) ask an evidence-based question; (2) search MEDLINE for the best evidence; (3) critically appraise the evidence; and (4) apply the evidence to the patient. The procedure is demonstrated with the sample question, Does bleaching of bonded porcelain veneers increase marginal leakage? A MEDLINE search strategy was developed for synonyms of the key words that best identify the problem, the intervention, and the outcome. The synonyms were combined using the Boolean operator "or" to identify a "sensitive" (i.e., inclusive) universe of 140,000 journal articles. These categories were then combined using the Boolean operator "and" to identify the most "specific" (i.e., exclusive) four articles from among the 140,000. Finally, to find the best evidence, the articles were limited to "humans" and "randomized controlled trials." This identified one article. Critical appraisal of the limited data in this one article indicates that the methods are valid and statistically significant, but because of the methods employed, may not be clinically important. Evidence-based methods take one to the edge of the available information universe in about 15 minutes. The results can be both exhilarating and sobering. They can indicate the depth or limits of available information and suggest gaps in the knowledge-base that require further study. Most importantly, however, the results allow practitioners to communicate incisively and truthfully with patients and to make more informed clinical choices.