Synthesis and structural analysis of 2-quinuclidonium tetrafluoroborate

The amide functional group is one of the most fundamental motifs found in chemistry and biology, and it has been studied extensively for the past century. Typical acyclic amides are planar. But the amide groups of bicyclic bridgehead lactams are highly twisted, and this distortion from planarity can dramatically affect the stability and reactivity of these amides; it also increases the basicity of the nitrogen so that it often behaves more like an amine than a typical planar amide. As a result, the structures and reactivity profiles of these 'anti-Bredt' amides differ significantly from those of planar amides. It is possible that this twisting phenomenon is not exclusive to cyclic systems—non-planarity may also be a critical biological design element that leads to amide ground-state destabilization and alters the reactivity, selectivity and mechanism of various protein and enzymatic processes (such as amide hydrolysis). The intriguing qualities of these twisted amides were first recognized in 1938 (ref. 11), wherein one of the simplest families was introduced—molecules containing the 1-azabicyclo[2.2.2]octan-2-one system. But the parent member of this group, 2-quinuclidone (molecule 1 in this paper), has not yet been unambiguously synthesized. Here, we report the chemical synthesis, isolation and full characterization of the HBF_4 salt of 1. Critical to the success of the synthesis and isolation was the decision to generate 1 by a route other than classical amide bond formation. We anticipate that these results will provide a greater understanding of the properties of amide bonds

Research on Intelligent Fuzzy Optimal Active and Hybrid Control Systems of Building Structures - Verification of Optimization Method on Switching Rules of Control Forces

Recently, many reseraches on active control systems of building structures are preformed based on modern control theory and are installed real buildings. The authors have already proposed intelligent fuzzy optimal active control (IFOAC) systems. IFOAC systems imitate intelligent activities of human brains such as prediction, adaptation, decision-kaking and so on. In IFOAC systems, objective and subjective judgements on the active control can be taken into account. However, IFOAC systems are considered to be suitable for far-field erathquake and control effect becomes small in case of near-field earthqaukes which include a few velosity pules with large amplitudes. To improve control effect in case of near-souece earthquakes, the authors have also proposed hybrid control (HC) systems, in which IFOAC systems and fuzzy control system are combined. In HC systems, the fuzzy control systems are introduced as a reflective fuzzy active control (RFAC) system and imitates spinal reflection of human. In HC systems, active control forces are activated to buildings in accordance with switching rules on active control forces. In this paper, optimizations on fuzzy control rules in RFAC system and switching rules of active control forces in HC system are performed by Parameter-Free Genetic Algorithms (PfGAs). Here, the optimization is performed by using different earthquake inputs. The results of digital simulations show that the HC system can reduce maximal response displacements under restrictions on strokes of the actuator effectively in case of a near-source earthquake and the effectiveness of the proposed HC system is discussed and clarified

A Facile and Modular Synthesis of Phosphinooxazoline Ligands

The copper(I) iodide catalyzed phosphine/aryl halide coupling procedure of Buchwald et al. provides modular, robust, and scaleable access to phosphinooxazoline (PHOX) ligands. The advantages of this method are highlighted by the convenient synthesis of PHOX ligands with varied steric and electronic properties, which would be challenging to synthesize by other protocols

A Facile and Modular Synthesis of Phosphinooxazoline Ligands

The copper(I) iodide catalyzed phosphine/aryl halide coupling procedure of Buchwald et al. provides modular, robust, and scaleable access to phosphinooxazoline (PHOX) ligands. The advantages of this method are highlighted by the convenient synthesis of PHOX ligands with varied steric and electronic properties, which would be challenging to synthesize by other protocols

Oligomerization of Hepatitis C Virus Core Protein is Crucial for Interaction with the Cytoplasmic Domain of E1 Envelope Protein

Hepatitis C virus (HCV) contains two membrane-associated envelope glycoproteins, E1 and E2, which assemble as a heterodimer in the endoplasmic reticulum (ER). In this study, predictive algorithms and genetic analyses of deletion mutants and glycosylation site variants of the E1 glycoprotein were used to suggest that the glycoprotein can adopt two topologies in the ER membrane: the conventional type I membrane topology and a polytopic topology in which the protein spans the ER membrane twice with an intervening cytoplasmic loop (amino acid residues 288 to 360). We also demonstrate that the E1 glycoprotein is able to associate with the HCV core protein, but only upon oligomerization of the core protein in the presence of tRNA to form capsid-like structures. Yeast two-hybrid and immunoprecipitation analyses reveal that oligomerization of the core protein is promoted by amino acid residues 72 to 91 in the core. Furthermore, the association between the E1 glycoprotein and the assembled core can be recapitulated using a fusion protein containing the putative cytoplasmic loop of the E1 glycoprotein. This fusion protein is also able to compete with the intact E1 glycoprotein for binding to the core. Mutagenesis of the cytoplasmic loop of E1 was used to define a region of four amino acids (residues 312 to 315) that is important for interaction with the assembled HCV core. Taken together, our studies suggest that interaction between the self-oligomerized HCV core and the E1 glycoprotein is mediated through the cytoplasmic loop present in a polytopic form of the E1 glycoprotein

New Hepatic Resection Criteria for Intermediate-Stage Hepatocellular Carcinoma Can Improve Long-Term Survival: A Retrospective, Multicenter Collaborative Study.

Background:Hepatic resection (HR) is not recommended for intermediate-stage hepatocellular carcinoma (HCC) by the Barcelona Clinic Liver Cancer criteria. We examined the prognostic factors of HR for intermediate-stage HCC and developed new HR criteria for intermediate-stage HCC.Methods:A total of 110 patients who underwent HR without any prior treatment for intermediate-stage HCC between January 2007 and December 2012 were enrolled at eight university hospitals. The outcomes and prognostic factors of HR were evaluated to develop new HR criteria.Results:In terms of tumor size and number, the most significant prognostic factors were within the up-to-seven criteria. Furthermore, serum albumin level ≥35 g/L and serum alpha-fetoprotein (AFP) level

Enantioselective Decarboxylative Alkylation Reactions: Catalyst Development, Substrate Scope, and Mechanistic Studies

α-Quaternary ketones are accessed through novel enantioselective alkylations of allyl and propargyl electrophiles by unstabilized prochiral enolate nucleophiles in the presence of palladium complexes with various phosphinooxazoline (PHOX) ligands. Excellent yields and high enantiomeric excesses are obtained from three classes of enolate precursor: enol carbonates, enol silanes, and racemic β-ketoesters. Each of these substrate classes functions with nearly identical efficiency in terms of yield and enantioselectivity. Catalyst discovery and development, the optimization of reaction conditions, the exploration of reaction scope, and applications in target-directed synthesis are reported. Experimental observations suggest that these alkylation reactions occur through an unusual inner-sphere mechanism involving binding of the prochiral enolate nucleophile directly to the palladium center