Alkoxyallene‐Based LANCA Three‐Component Synthesis of 1,2‐Diketones, Quinoxalines, and Unique Isoindenone Dimers and a Computational Study of the Isoindenone Dimerization

A series of β‐alkoxy‐β‐ketoenamides was prepared by the well‐established LANCA three‐component reaction of lithiated 1‐(2‐trimethylsilylethoxy)‐substituted allenes, nitriles, and α,β‐unsaturated carboxylic acids. The α‐tert‐butyl‐substituted compounds were smoothly converted into the expected 1,2‐diketones by treatment with trifluoroacetic acid. A subsequent condensation of the 1,2‐diketones with o‐phenylenediamine provided the desired highly substituted quinoxalines in good overall yield. Surprisingly, the α‐phenyl‐substituted β‐alkoxy‐β‐ketoenamides investigated afford not only the expected 1,2‐diketones, but also pentacyclic compounds with an anti‐tricyclo[4.2.1.12,5]deca‐3,7‐diene‐9,10‐dione core. These interesting products are very likely the result of an isoindenone dimerization which was mechanistically studied with the support of DFT calculations. Under the strongly acidic reaction conditions, a stepwise reaction is likely leading to a protonated isoindenone as reactive intermediate. It may first form a van der Waals complex with a neutral isoindenone before the two regio‐ and diastereoselective ring forming steps occur. Interestingly, two neutral or two protonated isoindenones are also predicted to dimerize giving the observed pentacyclic product

Safety of nevirapine in HIV-infected pregnant women initiating antiretroviral therapy at higher CD4 counts: A systematic review and meta-analysis

Background. The package insert for nevirapine (NVP) cautions against use in HIV-infected women (including pregnant women) with CD4 counts .250 cells/ƒÊl. However, recent studies showed that the CD4 count of pregnant women receiving antiretroviral therapy (ART) was not predictive of NVP toxicity.Objectives. To determine whether ART-naive pregnant women initiating NVP-based ART at higher CD4 counts experience greater toxicity compared with pregnant women at lower CD4 counts.Methods. We reviewed studies comparing serious adverse NVPrelatedevents among ART-naive pregnant women who commenced therapy at higher v. lower CD4 counts. Relevant studies were extracted from PubMed, SCOPUS and EMBASE, major journals and conference proceedings prior to December 2011. Authors were contacted for additional data. Data were independently extracted and entered into Review Manager.Results. Fourteen studies (2 663 participants) were included for analysis. The odds ratio (OR) for overall NVP toxicity among pregnant women with CD4 <250 cells/ƒÊl was 0.61 (95% confidence interval (CI) 0.43 - 0.85). When analysis was restricted to prospective studies only (7 studies, 1 318 participants), the results were consistent for overall NVP toxicity (OR 0.43; 95% CI 0.25 - 0.73) and severe hepatotoxicity (OR 0.45; 95% CI 0.22 - 0.90), but not for severe cutaneous reaction (OR 0.53; 95% CI 0.26 - 1.10).Conclusion. Initiating NVP-based ART during pregnancy at CD4 .250 cells/ƒÊl increases toxicity risk and should be avoided, necessitating urgent revision of current guidelines supporting this practice

Elastic properties of graphene flakes: boundary effects and lattice vibrations

We present a calculation of the free energy, the surface free energy and the elastic constants ("Lam'e parameters" i.e, Poisson ratio, Young's modulus) of graphene flakes on the level of the density functional theory employing different standard functionals. We observe that the Lam'e parameters in small flakes can differ from the bulk values by 30% for hydrogenated zig-zag edges. The change results from the edge of the flake that compresses the interior. When including the vibrational zero point motion, we detect a decrease in the bending rigidity by ~26%. This correction is depending on the flake size, N, because the vibrational frequencies flow with growing N due to the release of the edge induced compression. We calculate Grueneisen parameters and find good agreement with previous authors.Comment: 11 pages, 12 figure