Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 28
Filter
Add more filters










Publication year range
1.
Water Res ; 220: 118649, 2022 Jul 15.
Article in English | MEDLINE | ID: mdl-35635915

ABSTRACT

In many parts of the world, climate change has already caused a decline in groundwater recharge, whereas groundwater demand for drinking water production and irrigation continues to increase. In such regions, groundwater tables are steadily declining with major consequences for groundwater-surface water interactions. Predominantly gaining streams that rely on discharge of groundwater from the adjacent aquifer turn into predominantly losing streams whose water seeps into the underground. This reversal of groundwater-surface water interactions is associated with an increase of low river flows, drying of stream beds, and a switch of lotic ecosystems from perennial to intermittent, with consequences for fluvial and groundwater dependent ecosystems. Moreover, water infiltrating from rivers and streams can carry a complex mix of contaminants. Accordingly, the diversity and concentrations of compounds detected in groundwater has been increasing over the past decades. During low flow, stream and river discharge may consist mainly of treated wastewater. In losing stream systems, this contaminated water seeps into the adjoining aquifers. This threatens both ecosystems as well as drinking and irrigation water quality. Climate change is therefore severely altering landscape water balances, with groundwater-surface water-interactions having reached a tipping point in many cases. Current model projections harbor huge uncertainties and scientific evidence for these tipping points remains very limited. In particular, quantitative data on groundwater-surface water-interactions are scarce both on the local and the catchment scale. The result is poor public or political awareness, and appropriate management measures await implementation.


Subject(s)
Climate Change , Groundwater , Rivers , Water Quality , Ecosystem , Environmental Monitoring
2.
BMC Psychiatry ; 21(1): 294, 2021 06 07.
Article in English | MEDLINE | ID: mdl-34098932

ABSTRACT

BACKGROUND: Body dysmorphic disorder (BDD), defined as the obsessive idea that some aspect of one's own body or appearance is severely flawed/deformed, is relatively common in the general population and has been shown to have strong associations with mood and anxiety disorders and substance abuse disorders. Furthermore, a previous study on symptoms of BDD among people in the military showed that muscles are an important area of preoccupation. Hence, this study aimed to 1. assess the prevalence of BDD symptoms in Swiss military recruits, 2. specify the areas of preoccupation, and 3. analyze associated features (depression and alcohol/drug abuse). METHOD: A total of 126 Swiss male military recruits (age: M = 20.12, SD = 1.09, range: 18-24) were examined using self-report measurements to assess symptoms of BDD, depression, alcohol/drug abuse. RESULTS: The results showed that symptoms of BDD were relatively common (9.5% reached the cutoff value for probable BDD, 84% reported some symptoms), with the muscles as the most common area of preoccupation. A positive correlation (r = .38, p < .001) between depressive symptoms and symptoms of BDD was found, thus no correlation between alcohol/drug abuse and symptoms of BDD. CONCLUSION: The results indicate a need to develop and implement measures for prevention (e.g. raising awareness among the military) and intervention in this specific population.


Subject(s)
Body Dysmorphic Disorders , Military Personnel , Body Dysmorphic Disorders/diagnosis , Body Dysmorphic Disorders/epidemiology , Humans , Male , Prevalence , Self Report , Switzerland/epidemiology
3.
Org Lett ; 22(8): 3145-3148, 2020 04 17.
Article in English | MEDLINE | ID: mdl-32250124

ABSTRACT

Using an intramolecular nitrone cycloaddition and a Heck cyclization as the crucial transformations, a total synthesis of the racemic morphine alkaloid thebainone A was accomplished in 22 steps commencing with isovanillin.

4.
Molecules ; 23(6)2018 06 09.
Article in English | MEDLINE | ID: mdl-29890747

ABSTRACT

The tetracyclic pyrido[4,3-b]carbazole olivacine and four of its oxygenated derivatives have been synthesized by a late-stage palladium-catalyzed Heck-type cyclization of the pyrrole ring as a key step. In a test for the inhibition of the growth of Mycobacterium tuberculosis, 9-methoxyolivacine showed the most significant inhibitory activity against Mycobacterium tuberculosis, with an MIC90 value of 1.5 µM.


Subject(s)
Ellipticines/chemical synthesis , Ellipticines/pharmacology , Mycobacterium tuberculosis/drug effects , Oxygen/chemistry , Carbon-13 Magnetic Resonance Spectroscopy , Crystallography, X-Ray , Cyclization , Microbial Sensitivity Tests , Proton Magnetic Resonance Spectroscopy , Spectrometry, Mass, Electrospray Ionization , Spectrophotometry, Ultraviolet
5.
Org Lett ; 20(3): 832-835, 2018 02 02.
Article in English | MEDLINE | ID: mdl-29356553

ABSTRACT

Desymmetrization of a p-quinone monoacetal by organocatalytic sulfa-Michael addition provided rapid access to a C-ring building block for a formal synthesis of (-)-codeine. By means of a diastereoselective 1,2-addition for A/C-ring union, an intramolecular nitrone cycloaddition for construction of the phenanthrene core, and a sulfoxide elimination, an enantiopure key intermediate of the authors' previous synthesis of racemic codeine was available in 12 steps from isovanillin.

6.
Angew Chem Int Ed Engl ; 56(50): 15861-15865, 2017 12 11.
Article in English | MEDLINE | ID: mdl-28960721

ABSTRACT

The first total synthesis of the title diterpene was accomplished starting from the Wieland-Miescher ketone. A diastereoselective sulfa-Michael addition enabled the generation of the delicate ß,γ-unsaturated ketone moiety, while the tetracyclic kempane skeleton was readily constructed through domino metathesis.


Subject(s)
Diterpenes/chemical synthesis , Diterpenes/isolation & purification , Isoptera/chemistry , Animals , Diterpenes/chemistry , Molecular Conformation , Stereoisomerism
7.
Forensic Sci Int Genet ; 28: 52-70, 2017 05.
Article in English | MEDLINE | ID: mdl-28171784

ABSTRACT

Human DNA profiling using PCR at polymorphic short tandem repeat (STR) loci followed by capillary electrophoresis (CE) size separation and length-based allele typing has been the standard in the forensic community for over 20 years. Over the last decade, Next-Generation Sequencing (NGS) matured rapidly, bringing modern advantages to forensic DNA analysis. The MiSeq FGx™ Forensic Genomics System, comprised of the ForenSeq™ DNA Signature Prep Kit, MiSeq FGx™ Reagent Kit, MiSeq FGx™ instrument and ForenSeq™ Universal Analysis Software, uses PCR to simultaneously amplify up to 231 forensic loci in a single multiplex reaction. Targeted loci include Amelogenin, 27 common, forensic autosomal STRs, 24 Y-STRs, 7 X-STRs and three classes of single nucleotide polymorphisms (SNPs). The ForenSeq™ kit includes two primer sets: Amelogenin, 58 STRs and 94 identity informative SNPs (iiSNPs) are amplified using DNA Primer Set A (DPMA; 153 loci); if a laboratory chooses to generate investigative leads using DNA Primer Set B, amplification is targeted to the 153 loci in DPMA plus 22 phenotypic informative (piSNPs) and 56 biogeographical ancestry SNPs (aiSNPs). High-resolution genotypes, including detection of intra-STR sequence variants, are semi-automatically generated with the ForenSeq™ software. This system was subjected to developmental validation studies according to the 2012 Revised SWGDAM Validation Guidelines. A two-step PCR first amplifies the target forensic STR and SNP loci (PCR1); unique, sample-specific indexed adapters or "barcodes" are attached in PCR2. Approximately 1736 ForenSeq™ reactions were analyzed. Studies include DNA substrate testing (cotton swabs, FTA cards, filter paper), species studies from a range of nonhuman organisms, DNA input sensitivity studies from 1ng down to 7.8pg, two-person human DNA mixture testing with three genotype combinations, stability analysis of partially degraded DNA, and effects of five commonly encountered PCR inhibitors. Calculations from ForenSeq™ STR and SNP repeatability and reproducibility studies (1ng template) indicate 100.0% accuracy of the MiSeq FGx™ System in allele calling relative to CE for STRs (1260 samples), and >99.1% accuracy relative to bead array typing for SNPs (1260 samples for iiSNPs, 310 samples for aiSNPs and piSNPs), with >99.0% and >97.8% precision, respectively. Call rates of >99.0% were observed for all STRs and SNPs amplified with both ForenSeq™ primer mixes. Limitations of the MiSeq FGx™ System are discussed. Results described here demonstrate that the MiSeq FGx™ System meets forensic DNA quality assurance guidelines with robust, reliable, and reproducible performance on samples of various quantities and qualities.


Subject(s)
DNA Fingerprinting , High-Throughput Nucleotide Sequencing/instrumentation , Amelogenin/genetics , Animals , Female , Genotype , Humans , Male , Microsatellite Repeats , Polymerase Chain Reaction , Polymorphism, Single Nucleotide , Reproducibility of Results , Species Specificity
8.
Chemistry ; 22(47): 16897-16911, 2016 Nov 14.
Article in English | MEDLINE | ID: mdl-27778384

ABSTRACT

We describe a regioselective synthesis of 4- or 5-substituted carbazoles by oxidative cyclisation of meta-oxygen-substituted N-phenylanilines. Using the regiodirecting effect of a pivaloyloxy group, we prepared 4-hydroxycarbazole, a precursor for the enantiospecific synthesis of the ß-adrenoreceptor antagonists (-)-(S)-carazolol (5) and (-)-(S)-carvedilol (6). Regioselective palladium(II)-catalysed cyclisation of different diarylamines led to total synthesis of glycoborine (7) and the first total syntheses of the phytoalexin carbalexin A (8), glybomine A (9) and glybomine B (10). For glybomine B (10), a 5-hydroxycarbazole was converted into the corresponding triflate and utilized for introduction of a prenyl substituent.


Subject(s)
Carbazoles/chemical synthesis , Chemistry, Pharmaceutical/methods , Carvedilol , Catalysis , Cyclization , Models, Chemical , Oxidation-Reduction , Palladium/chemistry , Propanolamines/chemical synthesis , Sesquiterpenes/chemical synthesis , Spectrometry, Mass, Electrospray Ionization , Phytoalexins
9.
Org Lett ; 18(13): 3298-301, 2016 07 01.
Article in English | MEDLINE | ID: mdl-27333451

ABSTRACT

Relay metathesis enabled an improved access from (S)-citronellal to the marine trisnorguaiane (-)-clavukerin A. This hydroazulene was applied as an advantageously functionalized building block for the asymmetric synthesis of the sesquiterpene lactone osmitopsin and the proposed structure of 4,5-epoxyosmitopsin using a chemo-, regio-, and diastereoselective diepoxide opening as the key step.

10.
J Org Chem ; 80(11): 5666-73, 2015 Jun 05.
Article in English | MEDLINE | ID: mdl-25915067

ABSTRACT

We describe efficient synthetic routes to murrayamine A (mukoenine C), O-methylmurrayamine A, mahanine, O-methylmahanine, and murrayamine D and the first total syntheses of murrayamine E, I, and K. Key steps are a palladium-catalyzed construction of the carbazole framework and an annulation of the pyran ring, which is either catalyzed by phenylboronic acid or promoted by a Lewis acid.


Subject(s)
Alkaloids/chemistry , Carbazoles/chemistry , Carbazoles/chemical synthesis , Lewis Acids/chemistry , Catalysis , Molecular Structure , Stereoisomerism
11.
Int J Legal Med ; 129(1): 31-6, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25408291

ABSTRACT

The TruSeq™ Forensic Amplicon library preparation protocol, originally designed to attach sequencing adapters to chromatin-bound DNA for chromatin immunoprecipitation sequencing (TruSeq™ ChIP-Seq), was used here to attach adapters directly to amplicons containing markers of forensic interest. In this study, the TruSeq™ Forensic Amplicon library preparation protocol was used to detect 160 single nucleotide polymorphisms (SNPs), including human identification SNPs (iSNPs), ancestry, and phenotypic SNPs (apSNPs) in 12 reference samples. Results were compared with those generated by a second laboratory using the same technique, as well as to those generated by whole genome sequencing (WGS). The genotype calls made using the TruSeq™ Forensic Amplicon library preparation protocol were highly concordant. The protocol described herein represents an effective and relatively sensitive means of preparing amplified nuclear DNA for massively parallel sequencing (MPS).


Subject(s)
High-Throughput Nucleotide Sequencing , Polymorphism, Single Nucleotide , Sequence Analysis, DNA/methods , DNA Primers , Genetic Markers , Heterozygote , Humans , Real-Time Polymerase Chain Reaction
12.
Org Biomol Chem ; 12(23): 3866-76, 2014 Jun 21.
Article in English | MEDLINE | ID: mdl-24788002

ABSTRACT

Seven naturally occurring pyranocarbazole alkaloids (pyrayafoline A-E, O-methylmurrayamine A and O-methylmahanine) have been obtained by total synthesis using a palladium(II)-catalysed oxidative cyclisation of a diarylamine to an orthogonally diprotected 2,7-dihydroxycarbazole as key step.


Subject(s)
Alkaloids/chemical synthesis , Carbazoles/chemical synthesis , Chemistry, Organic/methods , Palladium/chemistry , Pyrans/chemical synthesis , Alkaloids/chemistry , Carbazoles/chemistry , Catalysis , Molecular Conformation , Pyrans/chemistry
13.
Angew Chem Int Ed Engl ; 52(44): 11651-5, 2013 Oct 25.
Article in English | MEDLINE | ID: mdl-24027174

ABSTRACT

A surprisingly selective, non-enzymatic kinetic resolution of readily available, racemic ß-chiral ketones enabled the title process, which was applied to a rapid synthesis of several bioactive flavanones in virtually enantiopure form (see scheme; MOM=methoxymethyl, Ts=p-toluenesulfonyl).


Subject(s)
Flavanones/chemistry , Biological Products , Catalysis , Hydrogenation , Molecular Structure , Stereoisomerism
14.
Hum Mutat ; 33(12): 1647-55, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22753075

ABSTRACT

Germline mutations in the human DNA mismatch repair (MMR) genes MSH2 and MLH1 are associated with the inherited cancer disorder Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer or HNPCC. A proportion of MSH2 and MLH1 mutations found in suspected LS patients give rise to single amino acid substitutions. The functional consequences in regard to pathogenicity of many of these variants are unclear. We have examined the functionality of a panel of MLH1 missense mutations found in LS families, by testing the variant proteins in functional assays, addressing subcellular localization, and protein-protein interaction with the dimer partner PMS2 and the MMR-associated exonuclease 1. We show that a significant proportion of examined variant proteins have functional defects in either subcellular localization or protein-protein interactions, which is suspected to lead to the cancer phenotype observed in patients. Moreover, the obtained results correlate well with reported MMR activity and with in silico analysis for a majority of the variants.


Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Mutation, Missense , Nuclear Proteins/genetics , Adaptor Proteins, Signal Transducing/chemistry , Adaptor Proteins, Signal Transducing/metabolism , Adenosine Triphosphatases/chemistry , Animals , DNA Repair Enzymes/chemistry , DNA-Binding Proteins/chemistry , Escherichia coli Proteins/chemistry , HeLa Cells , Humans , Mice , Mismatch Repair Endonuclease PMS2 , Models, Molecular , MutL Protein Homolog 1 , MutL Proteins , Mutagenesis, Site-Directed , NIH 3T3 Cells , Nuclear Proteins/chemistry , Nuclear Proteins/metabolism , Polymorphism, Single Nucleotide , Protein Binding , Protein Structure, Tertiary , Protein Transport , Structural Homology, Protein
15.
Chemistry ; 18(3): 770-6, 2012 Jan 16.
Article in English | MEDLINE | ID: mdl-22170766

ABSTRACT

Pd(II) caught in the act: The diaryl Pd(II) intermediate of a Pd(II)-catalyzed oxidative biaryl bond formation proceeding via a double C-H bond activation has been isolated and fully characterized, including an X-ray crystal structure analysis. Stabilization due to chelation by adjacent pivaloyloxy and acetyl groups has allowed the isolation of this long-sought crucial intermediate. On gentle warming, the complex is transformed into a carbazole product, and the catalytically active Pd(II) species is regenerated by oxidation with Cu(II).

16.
Chemistry ; 17(47): 13334-40, 2011 Nov 18.
Article in English | MEDLINE | ID: mdl-22012748

ABSTRACT

The first total synthesis of the macrodiolide antibiotic pamamycin-649B (1) was achieved by using sultone methodology. The diethyl substituted larger hydroxy acid fragment was constructed in a concise fashion through domino elimination/alkoxide-directed 1,6-additions of ethyllithium to sultones derived from intramolecular Diels-Alder reaction of furan-containing vinylsulfonates. Intermolecular Yamaguchi esterification of the two hydroxy acid building blocks and subsequent Yamaguchi cyclization eventually provided the target macrocycle 1. Since the final lactonization with formation of the ester linkage between C1' and the C8 oxygen proceeded with complete C2' epimerization, the more readily available C2' epimeric smaller fragment could be used to streamline the synthetic sequence.


Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Macrolides/chemistry , Macrolides/chemical synthesis , Cyclization , Molecular Structure , Stereoisomerism
17.
Org Biomol Chem ; 9(7): 2057-61, 2011 Apr 07.
Article in English | MEDLINE | ID: mdl-21279228

ABSTRACT

Iron-mediated oxidative cyclisation provides an efficient approach to pyrano[3,2-a]carbazole alkaloids. Thus, improved routes to girinimbine and murrayacine as well as the first total syntheses of O-methylmurrayamine A and 7-methoxymurrayacine are reported. Asymmetric epoxidation of girinimbine led to (-)-trans-dihydroxygirinimbine and the assignment of its absolute configuration.


Subject(s)
Carbazoles/chemistry , Carbazoles/chemical synthesis , Iron/chemistry , Alkaloids , Epoxy Compounds/chemistry , Models, Molecular , Molecular Structure , Stereoisomerism
18.
Chem Commun (Camb) ; 46(14): 2373-5, 2010 Apr 14.
Article in English | MEDLINE | ID: mdl-20379538

ABSTRACT

Bis-pyridylimine ligands with different linking elements are capable of forming unique hexanuclear circular Cu(II) meso-helicates; the self-assembly is controlled by coordination of sulfate ions to the metal centres.

20.
Dalton Trans ; (24): 4795-805, 2009 Jun 28.
Article in English | MEDLINE | ID: mdl-19513491

ABSTRACT

The interaction of Cu(II) with the following secondary N-substituted derivatives of di(2-picolyl)amine () are reported: N-cyclohexylmethyl-di(2-picolyl)amine (), N-benzyl-di(2-picolyl)amine (), N-(4-pyridylmethyl)-di(2-picolyl)amine (), N-(4-carboxymethylbenzyl)-di(2-picolyl)amine (), N-(9-anthracen-8-ylmethyl)-di(2-picolyl)amine (), 1,3-bis[di(2-picolyl)aminomethyl]benzene (), 1,4-bis[di(2-picolyl)aminomethyl]benzene () and 2,4,6-tris[di(2-picolyl)amino]triazine (). The solid complexes [Cu()(micro-Cl)](2)(PF(6))(2), [Cu()(micro-Cl)](2)(PF(6))(2).0.5CH(2)Cl(2), Cu()(ClO(4))(2), Cu()(2)(ClO(4))(2), [Cu()(ClO(4))(2)(H(2)O)].0.5H(2)O, Cu(2)()(ClO(4))(4), [Cu(2)()(Cl)(4)] and [Cu(2)(+H)(micro-OCH(3))(2)(H(2)O)](ClO(4))(3).C(4)H(10)O were isolated and X-ray structures of [Cu()(micro-Cl)](2)(PF(6))(2), [Cu()(micro-Cl)](2)(PF(6))(2).0.5CH(2)Cl(2,) [Cu()(2)(ClO(4))(2)(H(2)O)].0.5H(2)O, [Cu(2)()Cl(4)] and [Cu(2)(+H)(micro-OCH(3))(2)(H(2)O)](ClO(4))(3).C(4)H(10)O were obtained. The series is characterised by a varied range of coordination geometries and lattice architectures which in the case of [Cu()(ClO(4))(2)(H(2)O)].0.5H(2)O includes a chain-like structure formed by unusual intermolecular pi-interactions between metal bound perchlorate anions and the aromatic rings of adjacent anthracenyl groups. Variable temperature magnetic susceptibility measurements have been performed for [Cu()(micro-Cl)](2)(PF(6))(2) and [Cu()(micro-Cl)](2)(PF(6))(2).0.5H(2)O over the range 2-300 K. Both compounds show Curie-Weiss behaviour, with the data indicating weak antiferromagnetic interaction between the pairs of copper ions in each complex. Liquid-liquid (H(2)O/CHCl(3)) extraction experiments involving and as extractants showed that, relative to the parent (unsubstituted) dipic ligand , substitution at the secondary amine site in each case resulted in an increase in extraction efficiency towards Cu(II) (as its perchlorate salt); at least in part, this increase may be attributed to the enhanced lipophilicities of the N-substituted derivatives.


Subject(s)
Amines/chemistry , Copper/chemistry , Organometallic Compounds/chemistry , Picolinic Acids/chemistry , Anisotropy , Crystallography, X-Ray , Electron Spin Resonance Spectroscopy , Heterocyclic Compounds/chemical synthesis , Heterocyclic Compounds/chemistry , Magnetics , Models, Molecular , Molecular Conformation , Molecular Structure , Organometallic Compounds/chemical synthesis , Solvents/chemistry
SELECTION OF CITATIONS
SEARCH DETAIL
...