Convergent and flexible approach to stereodefined polyhydroxylated fragments

Stereodefined acyclic polyhydroxylated fragments characteristic to polyketide natural products could be easily prepared in good yields and excellent diastereoisomeric ratios from common and simple enol carbamates. The reaction provides these fragments through a combined, one-pot sequence of metalation, carbamoyl transfer, aldol reaction, and finally Tishchenko reduction. This strategy assembles up to five consecutive stereogenic centers with exceptional stereocontrol. 2009 Elsevier Ltd. All rights reserved.     

Asymmetric synthesis and molecular docking study of enantiomerically pure pyrrolidine derivatives with potential antithrombin activity

The (2R,4R,5S)- and (2S,4S,5R)-enantiomers of 4-(tert-butyl) 2-methyl 5-(4-bromophenyl)-pyrrolidine-2,4-dicarboxylate 3 were synthesized efficiently with an ee of >90% on a gram scale using a FAM-catalytic methodology. Subsequent modification afforded enantiopure N-((4-chlorophenyl)thio)acetyl pyrrolidine derivatives 4, which are potential thrombin inhibitors according to comprehensive molecular docking studies.     

Bispidinone-based molecular switches for construction of stimulus-sensitive liposomal containers

It is demonstrated that new lipid-like amphiphilic compounds, derivatives of 3,7-diazabicyclo[3.3.1]nonan-9-one (bispidinone) with long alkyl substituents, can be integrated into liposomal membranes. They can serve as molecular switches changing the conformation from the chair–boat to chair–chair on addition of an aqueous solution of a bivalent copper salt, and thus enhancing the permeability of the lipid bilayer of liposomes and the release of encapsulated compounds.     

Cross-language acoustic similarity predicts perceptual assimilation of Canadian English and Canadian French vowels

Monolingual Peruvian Spanish listeners identified natural tokens of the Canadian French (CF) and Canadian English (CE) /?/ and /?/, produced in five consonantal contexts. The results demonstrate that while the CF vowels were mapped to two different native vowels, /e/ and /a/, in all consonantal contexts, the CE contrast was mapped to the single native vowel /a/ in four out of five contexts. Linear discriminant analysis revealed that acoustic similarity between native and target language vowels was a very good predictor of context-specific perceptual mappings. Predictions are made for Spanish learners of the /?/-/?/ contrast in CF and CE.     

Tetraiododiborane(4) (B2I4) is a Polymer Based on sp3 Boron in the Solid State

Herein we present the first solid‐state structures of tetraiododiborane(4) (B₂I₄), which was long believed to exist in all phases as discrete molecules with planar, tricoordinate boron atoms, like the lighter tetrahalodiboranes(4) B₂F₄, B₂Cl₄, and B₂Br₄. Single‐crystal X‐ray diffraction, solid‐state NMR, and IR measurements indicate that B₂I₄ in fact exists as two different polymeric forms in the solid state, both of which feature boron atoms in tetrahedral environments. DFT calculations are used to simulate the IR spectra of the solution and solid‐state structures, and these are compared with the experimental spectra.     

Stereospecific Synthesis of β‐Lactams from Heterocyclic Imines Using the Staudinger Reaction

The reactions of the heterocyclic imines 5,6‐dihydro‐2H‐[1,3]oxazines and 2H‐1,4‐benzothiazines with different substituted acetyl chlorides in the presence of triethylamine forming β‐lactams were examined focusing on the stereochemistry of the Staudinger reaction.     

Analysis of Wavelength-Routed Optical Burst-Switched Network Performance

This paper studies a novel scalable network architecture combining optical burst switching (OBS) with dynamic wavelength allocation to guarantee quality of service (QoS), forming a wavelength-routed optical burst-switched network. All processing and buffering functions are concentrated at the network edge and bursts are assigned to fast tuneable lasers and routed over a bufferless optical transport core using dynamic wavelength assignment. Different burst aggregation mechanisms are evaluated for a range of traffic statistics in terms of delay and packet loss rate. New network performance parameters in an analytical model quantify the advantages of dynamic wavelength allocation. The results define the operational gain achievable with dynamic wavelength assignment compared to quasi-static wavelength routed optical networks.     

The Role of Single-Nucleotide Variants of NOS1, NOS2, and NOS3 Genes in the Comorbidity of Arterial Hypertension and Tension-Type Headache

Patients with tension-type headache (TTH) have an increased risk of developing arterial hypertension (AH), while hypertensive subjects do seem to have an increased risk of TTH. We searched for full-text English publications in databases using keywords and combined word searches over the past 15 years. In addition, earlier publications of historical interest were included in the review. In our review, we summed up the single nucleotide variants (SNVs) of Nitric Oxide Synthases (NOSs) genes involved in the development of essential AH and TTH. The results of studies we discussed in this review are contradictory. This might be due to different designs of the studies, small sample sizes in some of them, as well as different social and geographical characteristics. However, the contribution of genetic and environmental factors remains understudied. This makes the issue interesting for researchers, as understanding these mechanisms can contribute to a search for new approaches to pathogenetic and disease-modifying treatment of the AH and TTH phenotype. New drugs against AH and TTH can be based on inhibition of nitric oxide (NO) production, blockade of steps in the NO-cGMP pathway, or NO scavenging. Indeed, selective neuronal NOS (n-NOS) and inducible NOS (i-NOS) inhibitors are already in early clinical development.     

Human Lanosterol 14-Alpha Demethylase (CYP51A1) Is a Putative Target for Natural Flavonoid Luteolin 7,3′-Disulfate

Widespread pathologies such as atherosclerosis, metabolic syndrome and cancer are associated with dysregulation of sterol biosynthesis and metabolism. Cholesterol modulates the signaling pathways of neoplastic transformation and tumor progression. Lanosterol 14-alpha demethylase (cytochrome P450(51), CYP51A1) catalyzes one of the key steps in cholesterol biosynthesis. The fairly low somatic mutation frequency of CYP51A1, its druggability, as well as the possibility of interfering with cholesterol metabolism in cancer cells collectively suggest the clinical importance of CYP51A1. Here, we show that the natural flavonoid, luteolin 7,3′-disulfate, inhibits CYP51A1 activity. We also screened baicalein and luteolin, known to have antitumor activities and low toxicity, for their ability to interact with CYP51A1. The K_d values were estimated using both a surface plasmon resonance optical biosensor and spectral titration assays. Unexpectedly, in the enzymatic activity assays, only the water-soluble form of luteolin—luteolin 7,3′-disulfate—showed the ability to potently inhibit CYP51A1. Based on molecular docking, luteolin 7,3′-disulfate binding suggests blocking of the substrate access channel. However, an alternative site on the proximal surface where the redox partner binds cannot be excluded. Overall, flavonoids have the potential to inhibit the activity of human CYP51A1 and should be further explored for their cholesterol-lowering and anti-cancer activity.