Iron-Catalyzed Coupling of Alkenes and Enones: Sakurai-Michael-type Conjugate Addition of Catalytic Allyliron Nucleophiles.

The iron-catalyzed coupling of alkenes and enones through allylic C(sp3)-H functionalization is reported. This redox-neutral process employs a cyclopentadienyliron(II) dicarbonyl catalyst and simple alkene substrates to generate catalytic allyliron intermediates for 1,4-addition to chalcones and other conjugated enones. The use of 2,4,6-collidine as the base and a combination of triisopropylsilyl triflate and LiNTf2 as Lewis acids was found to facilitate this transformation under mild, functional group-tolerant conditions. Both electronically unactivated alkenes as well as allylbenzene derivatives could be employed as pronucleophilic coupling partners, as could a range of enones bearing electronically varied substituents.

Iron-Catalyzed Contrasteric Functionalization of Allenic C(sp2)-H Bonds: Synthesis of α-Aminoalkyl 1,1-Disubstituted Allenes.

An iron-catalyzed C-H functionalization of simple monosubstituted allenes is reported. An efficient protocol for this process was made possible by the use of a newly developed electron-rich and sterically hindered cationic cyclopentadienyliron dicarbonyl complex as the catalyst and N-sulfonyl hemiaminal ether reagents as precursors to iminium ion electrophiles. Under optimized conditions, the use of a mild, functional-group-tolerant base enabled the conversion of a range of monoalkyl allenes to their allenylic sulfonamido 1,1-disubstituted derivatives, a previously unreported and contrasteric regiochemical outcome for the C-H functionalization of electronically unbiased and directing-group-free allenes.

Corticosteroid sparing effects of vitamin C and magnesium in asthma: a randomised trial.

AIM: The study aims to assess the a priori hypothesis that regular supplementation with vitamin C or magnesium will permit a reduction in the corticosteroid dose required to maintain asthma control in adults. METHODS: We invited all participants recruited from primary care centres who completed a parallel-group, randomised, placebo-controlled, 16-week supplementation trial of 1g/day vitamin C or 450 mg/day magnesium to continue and participate in a structured corticosteroid reduction protocol over 10 weeks. RESULTS: A total of 92 participants (29 vitamin C, 31 magnesium and 32 placebo) entered the study. Assuming no reduction in corticosteroid dose in the 10 who subsequently withdrew, the geometric mean reductions in inhaled corticosteroid dose achieved with vitamin C, magnesium and placebo were 49, 13 and 11 microg, respectively. Relative to placebo, the unadjusted effect of vitamin C was significant, and remained at borderline significance after adjustment for baseline corticosteroid dose (relative reduction ratio=4.03, 95% CI 0.95 to 17.1, P=0.06). CONCLUSIONS: We conclude that while vitamin C supplements may have modest corticosteroid sparing effects and hence the potential to reduce exposure to their side effects, magnesium supplements have no effect on the inhaled corticosteroid dose required to maintain asthma control.

Increase in the prevalence of allergen skin sensitization in successive birth cohorts.

BACKGROUND: Little is known about longitudinal trends in the prevalence of allergen skin sensitization in the general population. OBJECTIVE: We sought to measure the change in prevalence of allergen skin sensitization over a 9-year period in a cohort of adults and hence to determine whether cross-sectional differences in prevalence between age groups are due to an aging or cohort effect. METHODS: In 1991 and 2000, we measured skin sensitization, defined as a wheal diameter of 3 mm or larger than that elicited by a saline control, to Dermatophagoides pteronyssinus, cat fur, mixed grass, Aspergillus fumigatus, and Cladosporium herbarum in a cohort of 1339 adults from Nottingham aged between 18 and 71 years in 1991. Subjects were divided into six 9-year successive birth cohorts, and the effects of birth cohort and the within-subject change from 1991 to 2000 were analyzed in a generalized estimating equation logit model. RESULTS: The unadjusted prevalence of sensitization to any allergen was 30.5% in 1991 and 31.8% in 2000. In cross-sectional analyses the prevalence of sensitization decreased with increasing age at both surveys (risk ratio, 2.15; 95% confidence interval [CI], 1.45-3.17 for 18- to 26-year-old patients relative to 63- to 70-year-old patients in the 1991 survey). In longitudinal analysis there was no within-subject change in sensitization from 1991 to 2000 (adjusted odds ratio, 1.07; 95% CI, 0.97-1.19), but there was a significant cohort effect (adjusted odds ratio per successive 9 year cohort, 1.27; 95% CI, 1.18-1.37). CONCLUSION: The cross-sectional decrease in allergen sensitization with age in the general population arises predominantly from a secular increase in sensitization prevalence with successive birth cohorts and not to a loss of sensitization within subjects over time. As a result of this cohort effect, the prevalence of allergic sensitization has increased in this general adult population sample.

Prospective study of diet and decline in lung function in a general population.

We have investigated the relationship between decline in lung function and dietary intakes of magnesium, vitamin C, and other antioxidant vitamins in a general population cohort in Nottingham, United Kingdom. In 1991, we measured dietary intake by semiquantitative food frequency questionnaire, forced expiratory volume in 1 second (FEV1), and respiratory symptoms in a cross-sectional survey of 2,633 adults aged 18-70. Nine years later we repeated these measures in 1,346 of these individuals. In cross-sectional analyses, after adjustment for smoking and other confounders, higher intakes of vitamin C and magnesium, but not vitamins A or E, were associated with higher levels of FEV1 in both 1991 and 2000. In longitudinal analysis with adjustment for confounders, decline in FEV1 between 1991 and 2000 was lower amongst those with higher average vitamin C intake by 50.8 ml (95% confidence interval, 3.8-97.9) per 100 mg of vitamin C per day, but was unrelated to magnesium intake. There was no relationship between decline in FEV1 and intake of vitamins A or E. This study suggests that a high dietary intake of vitamin C, or of foods rich in this vitamin, may reduce the rate of loss of lung function in adults and thereby help to prevent chronic obstructive pulmonary disease.