Retraction: Organocatalytic stereoselective synthesis of passifloricin A.

Retraction of 'Organocatalytic stereoselective synthesis of passifloricin A' by Pradeep Kumar et al., Org. Biomol. Chem., 2012, 10, 1820-1825.

Sugar-derived oxazolone pseudotetrapeptide as γ-turn inducer and anion-selective transporter.

The intramolecular cyclization of a C-3-tetrasubstituted furanoid sugar amino acid-derived linear tetrapeptide afforded an oxazolone pseudo-peptide with the formation of an oxazole ring at the C-terminus. A conformational study of the oxazolone pseudo-peptide showed intramolecular C=O···HN(II) hydrogen bonding in a seven-membered ring leading to a γ-turn conformation. This fact was supported by a solution-state NMR and molecular modeling studies. The oxazolone pseudotetrapeptide was found to be a better Cl--selective transporter for which an anion-anion antiport mechanism was established.

Acyclic αγα-Tripeptides with Fluorinated- and Nonfluorinated-Furanoid Sugar Framework: Importance of Fluoro Substituent in Reverse-Turn Induced Self-Assembly and Transmembrane Ion-Transport Activity.

Acyclic αγα-tripeptides derived from fluorinated-furanoid sugar amino acid frameworks act as reverse-turn inducers with a U-shaped conformation, whereas the corresponding nonfluorinated αγα-tripeptides show random peptide conformations. The NMR studies showed the presence of bifurcated weak intramolecular hydrogen bonding (F···HN) and N+···Fδ- charge-dipole attraction compel the amide carbonyl groups to orient antiperiplanar to the C-F bond, thus, demonstrating the role of the fluorine substituent in stabilizing the U-shaped conformation. The NOESY data indicate that the U-shaped tripeptides self-assembly formation is stabilized by the intermolecular hydrogen bonding between C═O···HN with antiparallel orientation. This fact is supported by ESI-MS data, which showed mass peaks up to the pentameric self-assembly, even in the gas phase. The morphological analysis by FE-SEM, on solid samples, showed arrangement of fibers into nanorods. The antiparallel self-assembled pore of the fluorinated tripeptides illustrates the selective ion-transport activity. The experimental findings were supported by DFT studies.

α-Geminal disubstituted pyrrolidine iminosugars and their C-4-fluoro analogues: Synthesis, glycosidase inhibition and molecular docking studies.

A simple strategy for the synthesis of α-geminal disubstituted pyrrolidine iminosugars 3a-c and their C-4 fluorinated derivatives 4a-c has been described from d-glucose. The methodology involves the Corey-Link and Jocic-Reeve reaction with 3-oxo-α-d-glucofuranose and nucleophilic displacement reaction to get the furanose fused pyrrolidine ring skeleton with requisite CH2OH/CO2H functionalities at C-3. The fluorine substituent in target molecules was introduced by nucleophilic displacement of -OTf in 9a/9c with CsF. Appropriate manipulation of the anomeric carbon in the furanose fused pyrrolidine ring skeleton afforded α-geminal disubstituted pyrrolidine iminosugars 3a-c and C-4 fluoro derivatives 4a-c. The pyrrolidine iminosugars 3a and 3c were found to be potent inhibitors of α-galactosidase while, the fluoro derivatives 4a and 4b showed strong inhibition of ß-glucosidase and ß-galactosidase, respectively. These results were substantiated by in silico molecular docking studies.

Synthesis of 2,4,6-Trisubstituted Pyridines by Oxidative Eosin Y Photoredox Catalysis.

Eosin Y, an organic dye, was activated as a photoredox catalyst in the presence of molecular oxygen using visible light and, when it was used in the reaction of aryl ketones and benzyl amines, afforded good yields (52-87%) of 2,4,6-triarylpyridines (21 examples) at ambient temperature. The aryl groups at the 2- and 6-positions are derived from ketones, while benzyl amine plays the dual role of providing an aryl functionality at the 4-position of pyridine as well as being a nitrogen donor.

Correction: Multivalent presentation of carbohydrates by 3(14)-helical peptide templates: synthesis, conformational analysis using CD spectroscopy and saccharide recognition.

Correction for 'Multivalent presentation of carbohydrates by 314-helical peptide templates: synthesis, conformational analysis using CD spectroscopy and saccharide recognition' by Nitin J. Pawar et al., Org. Biomol. Chem., 2015, 13, 11278-11285.

Synthesis of the C8'-epimeric thymine pyranosyl amino acid core of amipurimycin.

The C8'-epimeric pyranosyl amino acid core 2 of amipurimycin was synthesized from D-glucose derived alcohol 3 in 13 steps and 14% overall yield. Thus, the Sharpless asymmetric epoxidation of allyl alcohol 7 followed by trimethyl borate mediated regio-selective oxirane ring opening with azide, afforded azido diol 10. The acid-catalyzed 1,2-acetonide ring opening in 10 concomitantly led to the formation of the pyranose ring skeleton to give 2,7-dioxabicyclo[3.2.1]octane 12. Functional group manipulation in 12 gave 21 that on stereoselective ß-glycosylation afforded the pyranosyl thymine nucleoside 2 - a core of amipurimycin.

Multivalent presentation of carbohydrates by 3(14)-helical peptide templates: synthesis, conformational analysis using CD spectroscopy and saccharide recognition.

A well defined 314-helical tetravalent ß-galactopeptide site-specific functionalised template (SSFT) 1 was prepared containing d-galactose units, with free anomeric carbons as the aldehyde tags, and was explored via ligation with different aminoxy sugars (α-/ß-d-glucose, α/ß-d-galactose, α-d-mannose and ß-d-lactose) to get 314-helical carbohydrate-functionalised multivalent glycoconjugates 2-7. Preliminary recognition studies of tetramannosyl glycoconjugate 4 with a specific lectin (concanavalin A) using fluorescence anisotropy showed an increase in binding affinity and the multivalency effect was found to be increased by 6.5 times per glycan.

Azetidine- and N-carboxylic azetidine-iminosugars as amyloglucosidase inhibitors: synthesis, glycosidase inhibitory activity and molecular docking studies.

A simple strategy for the synthesis of hitherto unknown azetidine iminosugars 2a­2c and N-carboxylic azetidine iminosugar 2d has been reported. The methodology involves the conversion of 1,2:5,6-di-O-isopropylidene-3-oxo-α-D-glucofuranose 3 to 3-azido-3-deoxy-3-C-(formyl)-1,2:5,6-di-O-isopropylidene-α-D-glucofuranose 5 using the Jocic­Reeve and Corey­Link approaches. Compound 5 was transformed to 5-OTs 10/5-OMs 19 derivatives that on intramolecular nucleophilic displacement with in situ generated 3-amino functionality afforded the key azetidine ring skeletons 11 and 20, respectively. Hydrolysis of the 1,2-acetonide group and manipulation of the anomeric carbon in 12 provided azetidine iminosugars 2a­2c. In an attempt to synthesize azetidine iminosugars with an additional 4-hydroxymethyl group from 20, we encountered an interesting observation wherein the N-Cbz group in 20 hydrolyzed to the N-COOH functionality under TFA:H2O conditions that gave access for the synthesis of N-carboxylic azetidine iminosugar 2d. The glycosidase inhibitory activity of 2a­2d and intermediates 2e­f was studied with various glycosidases and was compared with Miglitol and 1-deoxynojirimycin (DNJ). Azetidine iminosugars 2 were found to inhibit amyloglucosidase with competitive type inhibition, amongst which 2d was found to be more active than Miglitol and DNJ. These results were substantiated by in silico molecular docking studies.

Diosgenin Functionalized Iron Oxide Nanoparticles as Novel Nanomaterial Against Breast Cancer.

Iron oxide nanoparticles (IONPs) have gained immense importance recently as drug nanocarriers due to easy multifunctionalization, simultaneous targeting, imaging and cancer hyperthermia. Herein, we report a novel nanomedicine comprising of IONPs core functionalized with a potent anticancer bioactive principle, diosgenin from medicinal plant Dioscorea bulbifera via citric acid linker molecule. IONPs were synthesized by reverse co-precipitation and characterized using field emission scanning electron microscopy (FESEM), high resolution transmission electron microscopy (HRTEM) and dynamic light scattering (DLS). Diosgenin functionalization was confirmed using fourier transform infrared spectroscopy (FTIR) and biochemical methods. Synthesized IONPs, citrate linked IONPs (IONPs-CA), diosgenin functionalized IONPs (IONPs-D) along with free citric acid and diosgenin were checked for anticancer activity against MCF7 breast cancer cells by MTT assay, wound migration assay, confocal microscopy and protein expression by western blotting. Size of IONPs, IONPs-CA and IONPs-D gradually increased ranging from 12 to 21 nm as confirmed by FESEM and HRTEM. Signature peaks of diosgenin at 2914, 1166 and 1444 cm-1 IONPs-D, revealed in FTIR indicated the presence of functionalized diosgenin. IONPs-D exhibited 51.08 ± 0.37% antiproliferative activity against MCF7 cells, which was found to be superior to free citric acid (17.71 ± 0.58%) and diosgenin (33.31 ± 0.37%). Treatment with IONPs-D exhibited reduced wound migration upto 40.83 ± 2.91% compared to bare IONPs (89.03 ± 2.58%) and IONPs-CA (50.35 ± 0.48%). IONPs-D and diosgenin exhibited apoptosis induction, confirmed by Alexa Fluor 488 annexin V/PI double-stained cells indicating extensive cell membrane damage coupled with PI influx leading to nuclear staining in treated cells. IONPs-D mediated selective PARP cleavage strongly rationalized it as superior apoptotic inducers. Based on these findings, IONPs-D can be considered as first diosgenin functionalized novel magnetic nanomedicine with antiproliferative, migration inhibiting and apoptosis inducing properties against breast cancer.

Synthesis of 1,5-dideoxy-1,5-iminoribitol C-glycosides through a nitrone-olefin cycloaddition domino strategy: identification of pharmacological chaperones of mutant human lysosomal ß-galactosidase.

We report herein a newly developed domino reaction that facilitates the synthesis of new 1,5-dideoxy-1,5-iminoribitol iminosugar C-glycosides 7a-e and 8. The key intermediate in this approach is a six-membered cyclic sugar nitrone that is generated in situ and trapped by an alkene dipolarophile via a [2 + 3] cycloaddition reaction to give the corresponding isooxazolidines 10a-e in a "one-pot" protocol. The iminoribitol C-glycosides 7a-e and 8 were found to be modest ß-galactosidase (bGal) inhibitors. However, compounds 7c and 7e showed "pharmacological chaperone" activity for mutant lysosomal bGal activity and facilitated its recovery in GM1 gangliosidosis patient fibroblasts by 2-6-fold.

γ-Hydroxyethyl piperidine iminosugar and N-alkylated derivatives: a study of their activity as glycosidase inhibitors and as immunosuppressive agents.

An efficient and practical strategy for the synthesis of (3R,4s,5S)-4-(2-hydroxyethyl) piperidine-3,4,5-triol and its N-alkyl derivatives 8a-f, starting from the D-glucose, is reported. The chiral pool methodology involves preparation of the C-3-allyl-α-D-ribofuranodialdose 10, which was converted to the C-5-amino derivative 11 by reductive amination. The presence of C-3-allyl group gives an easy access to the requisite hydroxyethyl substituted compound 13. Intramolecular reductive aminocyclization of C-5 amino group with C-1 aldehyde provided the γ-hydroxyethyl substituted piperidine iminosugar 8a that was N-alkylated to get N-alkyl derivatives 8b-f. Iminosugars 8a-f were screened against glycosidase enzymes. Amongst synthetic N-alkylated iminosugars, 8b and 8c were found to be α-galactosidase inhibitors while 8d and 8e were selective and moderate α-mannosidase inhibitors. In addition, immunomodulatory activity of compounds 8a-f was examined. These results were substantiated by molecular docking studies using AUTODOCK 4.2 programme.

Synthesis of (2S,3R)-3-amino-2-hydroxydecanoic acid and its enantiomer: a non-proteinogenic amino acid segment of the linear pentapeptide microginin.

A directed manipulation of the functional groups at C3 and C4 of D-glucose was demonstrated to synthesize naturally occurring (2S,3R)-α-hydroxy-ß-aminodecanoic acid (AHDA, 2a) and its enantiomer 2b. The enantiomer of 2a is the N-terminal part of the natural linear pentapeptide microginin, which is used as an antihypertensive agent.

Molecular architecture with carbohydrate functionalized ß-peptides adopting 314-helical conformation.

Carbohydrate recognition is essential in cellular interactions and biological processes. It is characterized by structural diversity, multivalency and cooperative effects. To evaluate carbohydrate interaction and recognition, the structurally defined attachment of sugar units to a rigid template is highly desired. ß-Peptide helices offer conformationally stable templates for the linear presentation of sugar units in defined distances. The synthesis and ß-peptide incorporation of sugar-ß-amino acids are described providing the saccharide units as amino acid side chain. The respective sugar-ß-amino acids are accessible by Michael addition of ammonia to sugar units derivatized as α,ß-unsaturated esters. Three sugar units were incorporated in ß-peptide oligomers varying the sugar (glucose, galactose, xylose) and sugar protecting groups. The influence of sugar units and the configuration of sugar-ß-amino acids on ß-peptide secondary structure were investigated by CD spectroscopy.

Sugar furanoid trans-vicinal diacid as a γ-turn inducer: synthesis and conformational study.

A simple method for the synthesis of a sugar furanoid trans vicinal diacid and its incorporation into the N-terminal tetrapeptide sequence (H-Phe-Trp-Lys-Thr-OH) to get glycopeptide has been described. 2D NMR and MD simulation studies of clearly show that the sugar diacid adopts a γ-turn conformation towards the N-terminus.

α-Geminal dihydroxymethyl piperidine and pyrrolidine iminosugars: synthesis, conformational analysis, glycosidase inhibitory activity, and molecular docking studies.

The Jocic-Reeve and Corey-Link type reaction of dichloromethyllithium with suitably protected 5-keto-hexofuranoses followed by treatment with sodium azide and sodium borohydride reduction gave 5-azido-5-hydroxylmethyl substituted hexofuranoses 7a-c with required geminal dihydroxymethyl group. Removal of protecting groups and converting the C-1 anomeric carbon into free hemiacetal followed by intramolecular reductive aminocyclization with in situ generated C5-amino functionality afforded corresponding 5C-dihydroxymethyl piperidine iminosugars 2a-c. Alternatively, removal of protecting groups in 7b and 7c and chopping of C1-anomeric carbon gave C2-aldehyde that on intramolecular reductive aminocyclization with C5-amino gave 4C-dihydroxymethyl pyrrolidine iminosugars 1b and 1c, respectively. On the basis of the (1)H NMR studies, the conformations of 2a/2b were assigned as (4)C(1) and that of 2c as (1)C(4). The glycosidase inhibitory activities of all five iminosugars were studied with various glycosidase enzymes and compared with natural d-gluco-1-deoxynojirimycin (DNJ). All the five compounds were found to be potent inhibitors of rice α-glucosidase with K(i) and IC(50) values in the nanomolar concentration range. Iminosugars 2b and 1b were found to be more potent inhibitors than their parent iminosugar. These results were substantiated by in silico molecular docking studies.

Organocatalytic stereoselective synthesis of passifloricin A.

The enantioselective synthesis of passifloricin A has been achieved in high diastereomeric excess. The 1,3-polyol moiety was constructed by iterative proline-catalyzed sequential α-aminoxylation and Horner-Wadsworth-Emmons (HWE) olefination of aldehydes while the synthesis of lactone moiety was achieved by ring-closing metathesis (RCM).

Gnidia glauca flower extract mediated synthesis of gold nanoparticles and evaluation of its chemocatalytic potential.

BACKGROUND: Novel approaches for synthesis of gold nanoparticles (AuNPs) are of utmost importance owing to its immense applications in diverse fields including catalysis, optics, medical diagnostics and therapeutics. We report on synthesis of AuNPs using Gnidia glauca flower extract (GGFE), its detailed characterization and evaluation of its chemocatalytic potential. RESULTS: Synthesis of AuNPs using GGFE was monitored by UV-Vis spectroscopy and was found to be rapid that completed within 20 min. The concentration of chloroauric acid and temperature was optimized to be 0.7 mM and 50°C respectively. Bioreduced nanoparticles varied in morphology from nanotriangles to nanohexagons majority being spherical. AuNPs were characterized employing transmission electron microscopy, high resolution transmission electron microscopy. Confirmation of elemental gold was carried out by elemental mapping in scanning transmission electron microscopic mode, energy dispersive spectroscopy and X-ray diffraction studies. Spherical particles of size ~10 nm were found in majority. However, particles of larger dimensions were in range between 50-150 nm. The bioreduced AuNPs exhibited remarkable catalytic properties in a reduction reaction of 4-nitrophenol to 4-aminophenol by NaBH4 in aqueous phase. CONCLUSION: The elaborate experimental evidences support that GGFE can provide an environmentally benign rapid route for synthesis of AuNPs that can be applied for various purposes. Biogenic AuNPs synthesized using GGFE exhibited excellent chemocatalytic potential.

Antidiabetic Activity of Gnidia glauca and Dioscorea bulbifera: Potent Amylase and Glucosidase Inhibitors.

Diabetes is a metabolic disorder affecting about 220 million people worldwide. One of the most critical complications of diabetes is post-prandial hyper-glycemia (PPHG). Glucosidase inhibitor and α-amylase inhibitors are class of compounds that help in managing PPHG. Low-cost herbal treatment is recommended due to their lesser side effect for treatment of diabetes. Two plants with significant traditional therapeutic potential, namely, Gnidia glauca and Dioscorea bulbifera, were tested for their efficiency to inhibit α-amylase and α-glucosidase. Stem, leaf, and flower of G. glauca and bulb of D. bulbifera were sequentially extracted with petroleum ether, ethyl acetate, and methanol as well as separately with 70% ethanol. Petroleum ether extract of flower of G. glauca was found to inhibit α-amylase significantly (78.56%). Extracts were further tested against crude murine pancreatic, small intestinal, and liver glucosidase enzyme which revealed excellent inhibitory properties. α-glucosidase inhibition provided a strong in vitro evidence for confirmation of both G. glauca and D. bulbifera as excellent antidiabetic remedy. This is the first report of its kind that provides a strong biochemical basis for management of type II diabetes using G. glauca and D. bulbifera. These results provide intense rationale for further in vivo and clinical study.

Repurposing of genistein as anti-sickling agent: elucidation by multi spectroscopic, thermophoresis, and molecular modeling techniques.

Sickle cell disease (SCD) is a major medical problem in which mono-therapeutic interventions have so far shown only limited effectiveness. We studied the repurpose of genistein, which could prevent sickle hemoglobin from polymerizing under hypoxic conditions in this disease. Genistein an important nutraceutical molecule found in soybean. The present study examines the repurposing genistein as an anti- sickling agent. Genistein shows inhibition of Hb S polymerization as well as a sickle reversal. Also, we have explored the interaction of the genistein with sickle hemoglobin (Hb S), using fluorescence, far-UV-CD spectroscopy, MicroScale Thermophoresis (MST), FTIR, combined with molecular modeling computations. The quenching constant decreases with increasing temperature, a characteristic that coincides with the static type of quenching mechanism. Temperature-dependent fluorescence measurements and molecular modeling studies reveal that apart from the hydrogen bonding, electrostatic interactions also play a crucial role in genistein and Hb S complex formation. In silico, distribution prediction of adsorption, digestion, metabolism, excretion, and toxicity (ADME/Tox) based on physical and chemical properties show that genistein is nontoxic and has ideal drug properties. The helicity and thermophoretic mobility of Hb S was a change in the presence of genistein, which leads to the destabilizing the Hb S polymer was examined using CD and MST, respectively. Our results open up the possibility for a promising therapeutic approach for the SCD by repurposed genistein as an anti-sickling agent.Communicated by Ramaswamy H. Sarma.