A Stereoselective Oxidative Dimerization En Route to (-)-Lomaiviticin A.

We describe a stereoselective synthesis of the dimeric diazofluorene , a potential precursor to the cytotoxic -symmetric bacterial metabolite (-)-lomaiviticin A (). An efficient route was developed to convert the tetracyclic diol to the diketone (five steps, 30% overall). Oxidative dimerization of the enoxysilane provided the -symmetric dimeric diazofluorene in 56% yield and with 15:1:0 diastereoselectivity.

Design and Semisynthesis of Biselectrophile-Functionalized Ubiquitin Probes To Investigate Transthioesterification Reactions.

Ubiquitin (Ub) regulates a wide array of cellular processes through post-translational modification of protein substrates. Ub is conjugated at its C-terminus to target proteins via an enzymatic cascade in which covalently bound Ub thioesters are transferred from E1 activating enzymes to E2 conjugating enzymes, and then to certain E3 protein ligases. These transthioesterification reactions proceed via transient tetrahedral intermediates.

Structure Elucidation of Secondary Metabolites: Current Frontiers and Lingering Pitfalls.

Analytical methods allow for the structure determination of submilligram quantities of complex secondary metabolites. This has been driven in large part by advances in NMR spectroscopic capabilities, including access to high-field magnets equipped with cryogenic probes. Experimental NMR spectroscopy may now be complemented by remarkably accurate carbon-13 NMR calculations using state-of-the-art DFT software packages.

Dementia's Unique Burden: Function and Health Care in the Last 4 Years of Life.

Background: Dementia is a terminal illness marked by progressive cognitive decline. This study characterized trajectories of functional status and health care use for people with and without dementia at the end of their life.

Methods: We used the Health and Retirement Study linked with Medicare claims to generate a series of generalized linear models.

Total synthesis of structurally diverse pleuromutilin antibiotics.

The emergence of drug-resistant bacterial pathogens has placed renewed emphasis on the total chemical synthesis of novel antibacterials. Tetracyclines, macrolides, streptogramins and lincosamides are now accessible through flexible and general synthetic routes. Pleuromutilins (antibiotics based on the fungal metabolite pleuromutilin) have remained resistant to this approach, in large part due to the difficulties encountered in the de novo construction of the decahydro-3a,9-propanocyclopenta[8]annulene skeleton.

Stereocontrolled Synthesis of the Fully Glycosylated Monomeric Unit of Lomaiviticin A.

We describe a stereocontrolled synthesis of , the fully glycosylated monomeric unit of the dimeric cytotoxic bacterial metabolite (-)-lomaiviticin A (). A novel strategy involving convergent, site- and stereoselective coupling of the β,γ-unsaturated ketone and the naphthyl bromide (92%, 15:1 diastereomeric ratio (dr)), followed by radical-based annulation and silyl ether cleavage, provided the tetracycle (57% overall), which contains the carbon skeleton of the aglycon of . The β-linked 2,4,6-trideoxy-4-aminoglycoside l-pyrrolosamine was installed in 73% yield and with 15:1 β:α selectivity using a modified Koenigs-Knorr glycosylation.

Video Teleconferencing for Disease Prevention, Diagnosis, and Treatment : A Rapid Review.

Background: Video teleconferencing (VTC) as a substitute for in-person health care or as an adjunct to usual care has increased in recent years.

Purpose: To assess the benefits and harms of VTC visits for disease prevention, diagnosis, and treatment and to develop an evidence map describing gaps in the evidence.

Data Sources: Systematically searched PubMed, EMBASE, Web of Science, and the Cochrane Library from 1 January 2013 to 3 March 2021.

Nearly One In Five Skilled Nursing Facilities Awarded Positive Incentives Under Value-Based Purchasing.

Medicare's Skilled Nursing Facility Value-Based Purchasing Program, which awards value-based incentive payments based on hospital readmissions, distributed its first two rounds of incentives during fiscal years 2019 and 2020. Incentive payments were based on achievement or improvement scores-whichever was better. Incentive payments were as low as -2.

Glycoconjugate synthesis using chemoselective ligation.

Chemoselective ligation of carbohydrates and polypeptides was achieved using an adipic acid dihydrazide cross-linker. The reducing end of a carbohydrate is efficiently attached to peptides in two steps, constructing a glycoconjugate in high yield and with high regioselectivity, enabling the production of homogeneous glycoconjugates.

c-fos proto-oncogene expression in human NK/LGL cells: expression is not constitutive and is associated with functional activation.

Unlike mature myeloid and monocytic cells and cell lines committed to terminal myelomonocytic differentiation, highly purified preparations of human natural killer cells/large granular lymphocytes (NK/LGL) did not spontaneously express the c-fos proto-oncogene. Transient expression of c-fos in NK/LGL was associated with functional activation with IL-2, IFN-gamma, LPS and PMA, which increased their cytotoxic activity, lymphokine secretion and in vitro chemotaxis. These results, together with the finding that T-cell receptor genes are in germ-line configuration in the vast majority of peripheral blood NK/LGL, are compatible with the hypothesis that these cells represent a separate hematopoietic lineage.