Enantioselective Cyclopropanation Catalyzed by Gold(I)-Carbene Complexes.

The formation of polysubstituted cyclopropane derivatives in the gold(I)-catalyzed reaction of olefins and propargylic esters is a potentially useful transformation to generate diversity, therefore any method in which its stereoselectivity could be controlled is of significant interest. We prepared and tested a series of chiral gold(I)-carbene complexes as a catalyst in this transformation. With a systematic optimization of the reaction conditions, we were able to achieve high enantioselectivity in the test reaction while the cis:trans selectivity of the transformation was independent of the catalyst. Using the optimized conditions, we reacted a series of various olefins and acetylene derivatives to find that, although the reactions proceeded smoothly and the products were usually isolated in good yield and with good to exclusive cis selectivity, the observed enantioselectivity varied greatly and was sometimes moderate at best. We were unable to establish any structure-property relationship, which suggests that for any given reagent combination, one has to identify individually the best catalyst.

Synthesis and Vibrational Circular Dichroism Analysis of N-Heterocyclic Carbene Precursors Containing Remote Chirality Centers.

VCD analysis of 16 diastereomeric pairs of NHC precursors containing two isolated chirality centers and different substitution patterns identified VCD transitions characteristic of the chirality center in the imidazolium ring or in the side chain, which, in contrast to ECD and OR, could be utilized to assign the two chirality centers separately by simple comparison, regardless of the type and position of achiral aromatic substituents. While the ECD and OR data showed great dependence on the position of an achiral substituent such as a methoxy group, characteristic experimental VCD transitions remained consistent and they could be used to determine the absolute configuration of all the regio- and stereoisomers and substituted analogues. VCD, ECD and OR approaches were evaluated, and several carbene precursors were found, for which only the VCD method could distinguish the four stereoisomers. With t-butyl, phenyl or 2-naphthyl substituents at the C-1' chirality center, the ECD spectra of the C-1' epimers were near-identical, and hence it was only the VCD approach that showed distinct differences suitable for the configurational assignment. The chiroptical characterization of our diastereomeric pairs of NHC precursors enables the future application of related derivatives having different substitution patterns in stereoselective transformations.

Acceptability of less than perfect health states in rheumatoid arthritis: the patients' perspective.

Some health problems are considered by many individuals as a 'normal' part of ageing. Our aim was to investigate whether patients with rheumatoid arthritis (RA) consider different types and levels of health losses as acceptable beyond a certain age. A multicenter cross-sectional survey was performed involving RA patients at the initiation of the first biological therapy. The EQ-5D and the Health Assessment Questionnaire Disability Index (HAQ-DI) questionnaires were used to describe domain-specific health states. Patients were asked to indicate for each domain from what age and onward (between ages 30 and 80 years in 10 year intervals) they considered moderate and severe problems acceptable or alternatively never acceptable. Seventy-seven RA patients (females 86%, mean age 50.3, disease duration 9.1 years) completed the questionnaire. Disease activity (DAS28), EQ-5D and HAQ-DI scores were mean 6.00 (SD 0.85), 0.35 (SD 0.36), 1.48 (SD 0.66), respectively. The majority of the patients considered age 70 and beyond as acceptable to have some health problems (EQ-5D: self-care 42%, pain/discomfort 34%, mobility 33%, usual activities 33%, anxiety/depression 27%), whilst at ages 30 and 40 as not acceptable. Severe health problems were mostly (57-69%) considered never acceptable, except the 'Usual activities' domain (acceptable from age 80 by 50.6%). The great majority of the patients (77-96%) were younger than what they indicated as the acceptability age limit. Similar results were found for the HAQ-DI. This small experimental study suggests that RA patients consider some health problems acceptable. This acceptability is age related and varies by health areas. Further larger studies are needed to explore explanatory variables and to compare with other diseases. Owing to the impact acceptability might have on RA patients' self-evaluation of current health state and decision-making, the topic deserves methodological improvement and further investigation.