ABSTRACT
Alkynyl addition to carbonyl compounds is a valuable synthetic method for the preparation of versatile chiral alcohols that are widely found in pharmaceuticals and natural products. Although a variety of enantioselective variations have been reported, alkynyl addition to simple ketones remains an unmet challenge due to their low reactivity and difficult enantiofacial discrimination. Here, we report a method for the catalytic enantioselective addition of lithium acetylide to a variety of ketones using macrocyclic lithium binaphtholates as catalysts. These reactions generally suffer from facile aggregation of lithium species, which leads to less active and selective catalysts. The macrocyclic structure designed in this study prevents such aggregation, affording a monomeric and highly active catalyst that can furnish enantioenriched tertiary alcohols from a variety of ketones within 5-30 min. Moreover, the confined cavity and lipophilicity of the macrocycle confer substrate specificity on the system, demonstrating a multiselectivity similar to that of enzymatic reactions. Thus, these findings offer new insights into the rational design of small-molecule artificial enzymes that exhibit high levels of reactivity and multiselectivity.
ABSTRACT
BBr3 -assisted chiral phosphoric acid catalysts for enantioselective [2+2] cycloaddition were developed. The reactions of phenyl vinyl sulfide with α-substituted acroleins proceeded, and the corresponding [2+2] cycloadducts were obtained with high enantioselectivity. In particular, the [2+2] cycloadduct obtained from methacrolein is a synthetically useful optically active cyclobutane, which could be transformed to a key intermediate for (+)-frontalin, a pheromone of Asian elephants.
ABSTRACT
Chicken cathelicidin-B1 (chCATH-B1) is a major host defense peptide of the chicken bursa of Fabricius (BF). To investigate the mechanisms of chCATH-B1 gene expression in the BF, we focused on the DT40 cell line derived from chicken bursal lymphoma as a model for analysis. A cDNA encoding chCATH-B1 precursor was cloned from DT40 cells. The nucleotide sequence of the cDNA was identical with that of the BF chCATH-B1. A broth dilution analysis showed that the synthetic chCATH-B1 exhibited a significant defensive activity against both Escherichia coli and Staphylococcus aureus. A scanning microscopic analysis demonstrated that chCATH-B1 inhibited bacterial growth through membrane destruction with formation of blebs and spheroplasts. Limulus amoebocyte lysate assay and electromobility shift assay results revealed that chCATH-B1 bound to lipopolysaccharide (LPS) and lipoteichoic acid (LTA), which are the surface substances of the E. coli and S. aureus cell, respectively. A chemotactic assay results revealed that chCATH-B1 showed mouse-derived P-815 mastocytoma migrating activity dose-dependently but with a higher concentration, resulting in a loss of the activity. A semi-quantitative real-time RT-PCR analysis revealed that LPS stimulated chCATH-B1 gene expression in a dose-dependent manner and that the LPS-inducible chCATH-B1 gene expression was inhibited by the administration of dexamethasone. The chCATH-B1 mRNA levels in DT40 cells were also increased by the administration of bacterial LTA. The results indicate that bacterial toxins induce chCATH-B1 gene expression in the chicken BF and the peptide expressed in the organ would act against pathogenic microorganisms not only directly but also indirectly by attracting mast cells.
Subject(s)
Antimicrobial Cationic Peptides/genetics , Antimicrobial Cationic Peptides/pharmacology , Bacterial Toxins/pharmacology , Gene Expression Regulation/drug effects , Lymphoma/genetics , Animals , Antimicrobial Cationic Peptides/metabolism , Bacterial Toxins/chemistry , Cell Line , Chickens , Cloning, Molecular , Dose-Response Relationship, Drug , Escherichia coli/drug effects , Gene Expression Regulation/genetics , Lymphoma/metabolism , Microbial Sensitivity Tests , RNA, Messenger/drug effects , RNA, Messenger/genetics , Staphylococcus aureus/drug effects , Structure-Activity RelationshipABSTRACT
Hyperthyroidism was induced by daily subcutaneous injections of L-thyroxine (T(4), 0.5 mg/kg/day) for 3 days, 1 week, or 2 weeks to study whether there is a fluctuation in adrenoceptor- and muscarinic receptor-mediated blood pressure responses at a hyperthyroid stage. T(4) treatment for 3 days or 1 week significantly suppressed the pressor response induced by norepinephrine (NE). The depressor responses induced by isoprenaline or acetylcholine (ACh) were increased by T(4) treatment for only 3 days. The pressor response induced by N(G)-nitro-L-arginine (L-NA) was increased by T(4) treatment for only 3 days. Results suggest that adrenoceptor- and muscarinic receptor-mediated blood pressure responses fluctuate in hyperthyroidism caused by T(4) in rats, that the basal nitric oxide (NO) production and/or release are increased in hyperthyroid rats at an early stage of the disease.