ABSTRACT
The functionalization of heteroarenes has been integral to the structural diversification of medicinally active molecules such as quinolines, pyridines, and phenanthridines. Electron-deficient heteroarenes are electronically compatible to react with relatively nucleophilic free radicals such as hydroxyalkyl. However, the radical functionalization of such heteroarenes has been marked by the use of transition-metal catalyzed processes that require initiators and stoichiometric oxidants. Herein, we describe the photochemical alkylation of quinolines, pyridines and phenanthridines, where through direct excitation of the protonated heterocycle, alcohols and ethers, such as methanol and THF, can serve as alkylating agents. We also report the discovery of a photochemical reduction of these heteroarenes using only iPrOH and HCl. Mechanistic studies to elucidate the underlying mechanism of these transformations, and preliminary results on catalytic methylations are also reported.
ABSTRACT
Protein-protein interaction (PPI) maps provide insight into cellular biology and have received considerable attention in the post-genomic era. While large-scale experimental approaches have generated large collections of experimentally determined PPIs, technical limitations preclude certain PPIs from detection. Recently, we demonstrated that yeast PPIs can be computationally predicted using re-occurring short polypeptide sequences between known interacting protein pairs. However, the computational requirements and low specificity made this method unsuitable for large-scale investigations. Here, we report an improved approach, which exhibits a specificity of approximately 99.95% and executes 16,000 times faster. Importantly, we report the first all-to-all sequence-based computational screen of PPIs in yeast, Saccharomyces cerevisiae in which we identify 29,589 high confidence interactions of approximately 2 x 10(7) possible pairs. Of these, 14,438 PPIs have not been previously reported and may represent novel interactions. In particular, these results reveal a richer set of membrane protein interactions, not readily amenable to experimental investigations. From the novel PPIs, a novel putative protein complex comprised largely of membrane proteins was revealed. In addition, two novel gene functions were predicted and experimentally confirmed to affect the efficiency of non-homologous end-joining, providing further support for the usefulness of the identified PPIs in biological investigations.
Subject(s)
Computational Biology/methods , Protein Interaction Mapping/methods , Saccharomyces cerevisiae Proteins/metabolism , Genome, Fungal , Peptides/chemistry , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae Proteins/analysis , Saccharomyces cerevisiae Proteins/chemistry , Sequence Analysis, ProteinABSTRACT
[figure: see text] alpha-, beta-, and gamma-Keto acids are reduced with diisopinocampheylborane at room temperature to the corresponding hydroxy acids with predictable stereochemistry in very high ee. The gamma-hydroxy acids produced were conveniently cyclized to the corresponding lactones. This provides a simple synthesis of 4-hexanolide, a component of the pheromone secreted by the female dermestid beetle Trogoderma glabrum.
Subject(s)
Boron Compounds/chemistry , Keto Acids/chemistry , Lactones/chemistry , Lactones/chemical synthesis , Pheromones , Animals , Catalysis , Coleoptera , Female , Molecular Conformation , Molecular Structure , Pheromones/chemistry , Pheromones/metabolismABSTRACT
All staff members are involved in the QA by exception process, empowering them to voice what is wrong with the system and giving them the opportunity to have an impact on improvement. Since the review of aspects of care is ongoing and all-encompassing, it allows for continuous improvement. Other reviews will be required; however, this comprehensive method of assessment can add to the value of your QA program. It provides accurate measurements and positive direction while facilitating quality improvement.
Subject(s)
Quality Assurance, Health Care , Technology, Radiologic , Technology, Radiologic/standardsABSTRACT
Two new anthraquinones have been isolated from the seeds of PEGANUM HARMALA Linn and the structures established as 3,6-dihydroxy-8-methoxy-2-methylanthraquinone (peganone; 1) and 8-hydroxy-7-methoxy-2-methylanthraquinone (peganone; 2) by spectral correlations and chemical evidences.