Synthesis of Bridged Inside–Outside Bicyclic Ethers through Oxidative Transannular Cyclization Reactions

The classical geometry of the 6-<i>endo</i> transition state for nucleophilic additions into oxocarbenium ions can be perturbed by incorporating the reactive groups into medium-sized rings, leading to the formation of 2,6-<i>trans</i>-dialkyl tetrahydropyrans. The bicyclic products exhibit inside–outside stereoisomerism, as seen in numerous macrolide natural products

Synthesis of Bridged Inside–Outside Bicyclic Ethers through Oxidative Transannular Cyclization Reactions

The classical geometry of the 6-<i>endo</i> transition state for nucleophilic additions into oxocarbenium ions can be perturbed by incorporating the reactive groups into medium-sized rings, leading to the formation of 2,6-<i>trans</i>-dialkyl tetrahydropyrans. The bicyclic products exhibit inside–outside stereoisomerism, as seen in numerous macrolide natural products

Tumor Necrosis Factor (<i>TNF</i>) –308G>A, Nitric Oxide Synthase 3 (<i>NOS3</i>) +894G>T Polymorphisms and Migraine Risk: A Meta-Analysis

<div><p>Background and Objective</p><p>Conflicting data have been reported on the association between tumor necrosis factor (<i>TNF</i>) –308G>A and nitric oxide synthase 3 (<i>NOS3</i>) +894G>T polymorphisms and migraine. We performed a meta-analysis of case-control studies to evaluate whether the <i>TNF</i> –308G>A and <i>NOS3 </i>+894G>T polymorphisms confer genetic susceptibility to migraine.</p><p>Method</p><p>We performed an updated meta-analysis for <i>TNF</i> –308G>A and a meta-analysis for <i>NOS3 </i>+894G>T based on studies published up to July 2014. We calculated study specific odds ratios (OR) and 95% confidence intervals (95% CI) assuming allele contrast, dominant model, recessive model, and co-dominant model as pooled effect estimates.</p><p>Results</p><p>Eleven studies in 6682 migraineurs and 22591 controls for <i>TNF</i> –308G>A and six studies in 1055 migraineurs and 877 controls for <i>NOS3</i> +894G>T were included in the analysis. Neither indicated overall associations between gene polymorphisms and migraine risk. Subgroup analyses suggested that the “A” allele of the <i>TNF</i> –308G>A variant increases the risk of migraine among non-Caucasians (dominant model: pooled OR = 1.82; 95% CI 1.15 – 2.87). The risk of migraine with aura (MA) was increased among both Caucasians and non-Caucasians. Subgroup analyses suggested that the “T” allele of the <i>NOS3</i> +894G>T variant increases the risk of migraine among non-Caucasians (co-dominant model: pooled OR = 2.10; 95% CI 1.14 – 3.88).</p><p>Conclusions</p><p>Our findings appear to support the hypothesis that the <i>TNF </i>–308G>A polymorphism may act as a genetic susceptibility factor for migraine among non-Caucasians and that the <i>NOS3</i> +894G>T polymorphism may modulate the risk of migraine among non-Caucasians.</p></div

Forest plot of migraine risk associated with the <i>NOS3</i> +894G>T polymorphism stratified by ethnicity under the TT vs. GG model.

<p>The boxes and horizontal lines represent the OR and the corresponding 95% CI. The areas of the boxes indicate the weight (inverse of the variance). The diamonds correspond to the summary OR and 95% CI.</p

One-way sensitivity analyses of the associations between genetic polymorphisms and migraine risk.

<p>A: One-way sensitivity analysis of the association between the <i>TNF</i> –308G>A polymorphism and migraine risk under the GA vs. GG model. B: One-way sensitivity analysis of the association between the <i>NOS3</i> +894G>T polymorphism and migraine risk under the T vs. G model.</p

Characteristics of the eligible studies in this meta-analysis.

<p>ICHD-II: International Classification of Headache Disorders-II; HIS: International Headache Society; HWE: Hardy-Weinberg equilibrium; PCR: polymerase chain reaction; RFLP: restriction fragment length polymorphism; ARMS: amplification refractory mutation system; SNPs: single nucleotide polymorphisms; RT-PCR: real-time polymerase chain reaction.</p><p>Y: consistent with HWE; F: female; M: male. NOS: Newcastle—Ottawa Quality Assessment Scale for Case Control Studies.</p><p>Characteristics of the eligible studies in this meta-analysis.</p

Forest plot of migraine with aura risk associated with the <i>TNF</i> –308G>A polymorphism stratified by ethnicity under the AA+GA vs. GG model.

<p>The boxes and horizontal lines represent the OR and the corresponding 95% CI. The areas of the boxes indicate the weight (inverse of the variance). The diamonds correspond to the summary OR and 95% CI.</p

Begg’s funnel plots for genetic polymorphisms.

<p>A: Begg’s funnel plot for the <i>TNF</i> –308G>A polymorphism. B: Begg’s funnel plot for the <i>NOS3</i> +894G>T polymorphism.</p

Flow chart of the study selection process.

<p>Flow chart of the study selection process.</p

Forest plot of migraine risk associated with the <i>TNF</i> –308G>A polymorphism stratified by ethnicity under the GA vs. GG model.

<p>The boxes and horizontal lines represent the OR and the corresponding 95% CI. The areas of the boxes indicates the weight (inverse of the variance). The diamonds correspond to the summary OR and 95% CI.</p