Total synthesis of (+)-UCS1025A based on a sequential Michael-retro Michael strategy featuring one-pot six-step cascade reaction

The asymmetric total synthesis of UCS1025A is accomplished by establishing a novel and efficient method for the construction of a tricyclic pyrrolizidinone skeleton based on a sequential Michael-retro Michael strategy. The key step is a one-pot six-step cascade reaction including oxidation of a primary alcohol to the corresponding carboxylic acid, a retro thio-Michael reaction, and an intramolecular oxy-Michael reaction. This newly-developed synthetic strategy inspired by “masked” electrophilic character of tricyclic pyrrolizidinone is efficient and high-yielding compared to that developed in previously-reported total syntheses.     

Single-Fluorophore Dynamic Imaging in Living Cells

Recently, observation and tracking of single fluorophores, which we term single fluorophore dynamic imaging (SFDI) in this review, in living cells have been achieved. In particular, the recent success of SFDI of individual proteins tagged with green fluorescent protein (GFP) in live cells has opened new important possibilities for studying events occurring in living cells at the level of single molecules. Specifically, SFDI of GFP allows the tracking of movement and oligomerization levels of individual oligomers (monomers) in living cells and, thus, provides powerful means to investigate the movement, assembly, localization, and activation that signaling molecules undergo following an external stimulus. In this short account, we first review technologically important points for SFDI of GFP molecules in living cells, then give examples of its application, and, finally, propose a synergistic use of SFDI and single-particle tracking, a technique used for investigating single or small groups of molecules in live cells over the past 15 years.     

Poly(arylene thioether)s containing 9,9′‐spirobifluorene moieties in the main chain: Masked dithiol‐based synthesis and excellent optical properties

Poly(arylene thioether)s ( PTEs ) containing 9,9′‐spirobifluorene moieties were synthesized in high yields from 9,9′‐spirobifluorene‐2,2′‐bis(N,N‐dimethylcarbamothioate) 4 as the masked dithiol and various difluoroarenes as electrophilic monomers. All PTEs showed high thermal stability: The 10% weight loss temperature as evaluated by thermogravimetric analysis was over 470 °C under both nitrogen and air atmospheres. The glass transition temperature estimated by DSC was in the range 210–270 °C. The PTEs showed high solubility in ordinary organic solvents, such as CHCl₃, NMP, and THF. Most PTEs exhibited remarkably high refractive indices ranging from 1.69 to 1.73 at 587.6 nm, whereas no or little birefringence was observed for the PTEs . © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 4192–4199, 2010     

Polymorphism-dependent fluorescence of 9,10-bis(pentafluorobenzoyloxy)anthracene

Anthracene derivatives possessing pentafluorobenzoyloxy moieties at 9- and 10-positions showed polymorphism affording two types of fluorescent crystals with blue and bluish green fluorescence in their crystalline state, respectively. Their single crystal X-ray structures showed that the degree of overlap of anthracene moieties was responsible for the difference in fluorescence. Fluorescence in the crystalline state originated in the dimer emission deduced from their excitation spectra.     

Copolymerization of 2‐isothiocyanatoethyl methacrylate and 2‐hydroxyethyl methacrylate or methacrylic acid based on a nucleophile‐tolerant property of the isothiocyanato group

Radical copolymerizations of 2‐isothiocyanatoethyl methacrylate (ITEMA) and 2‐hydroxyethyl methacrylate (HEMA) or methacrylic acid (MAA) were examined, and fundamental properties of the obtained copolymers were investigated. The copolymerizations of various ITEMA/HEMA or ITEMA/MAA compositions proceeded effectively in THF or DMF by using 2,2′‐azobisbutyronitrile (AIBN) as an initiator, keeping the isothiocyanato groups and hydroxyl or carboxyl groups unchanged. Glass transition temperatures (T_g)s of poly(ITEMA‐co‐HEMA)s ranged from 68 to 100 °C, and they were thermally stable up to 200 °C. Meanwhile, T_gs of poly(ITEMA‐co‐MAA)s (ITEMA/MAA = 91/9, 76/24) were determined to be 91 and 109 °C, respectively. However, poly(ITEMA‐co‐MAA)s were thermally unstable, and significant weight loss was observed around 180 °C, which may be due to an addition of carboxyl groups to isothiocyanato groups followed by an elimination of COS to form amide structure in the copolymers. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 5221–5229     

Water‐stable copolymers containing isocyanate moiety protected by hydrophobic styrene segment and their reaction with amines

Reactive isocyanate groups were protected and stabilized by the hydrophobic styrene segment and acquired high tolerance toward water. Copolymers containing isocyanate groups were synthesized by a radical copolymerization of 2‐propenyl isocyanate (2PI) and styrene (St). The stability of the obtained copolymers on water was examined to find that isocyanate groups were protected by the hydrophobic polystyrene segment and were stable on water and these isocyanates reacted with primary amines including amino acids to form urea selectively on water. Primary amines with a higher octanol‐water partition coefficient or smaller steric hindrance were more reactive to the isocyanate groups in the side chain of the copolymer. The protection of reactive isocyanate groups using the hydrophobic styrene segment did not give side products which are produced in the usual chemical protection/deprotection process. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 1934–1940     

Highly sensitive simultaneous quantification of indoxyl sulfate and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid in human plasma using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry

Indoxyl sulfate and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid are uremic toxins that accumulate in renal failure and have been reported to decrease the activities of the drug-metabolizing enzyme cytochrome P450 3A and the drug transporter organic anion transporting polypeptides 1B, respectively. In this study, we established and validated an assay for simultaneous quantification of indoxyl sulfate and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid in human plasma. The samples were pretreated by solid-phase extraction, and measured by ultra-high-performance liquid chromatography–tandem mass spectrometry. The validation results for this assay were within the acceptable limits recommended by the US Food and Drug Administration, with a lower limit of quantitation of 0.05 μg/mL for both indoxyl sulfate and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid. Recovery rates of indoxyl sulfate and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid corrected by internal standard were 100.7–101.9 and 100.2–101.3%, respectively. Matrix effects of indoxyl sulfate and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid corrected by internal standard were 101.1–105.5 and 97.0–103.8%, respectively. The validated assay was used to analyze indoxyl sulfate and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid concentrations in the plasma samples of healthy volunteers and patients with chronic kidney disease. All the measured plasma indoxyl sulfate and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid concentrations were within the calibration ranges. This novel method may contribute to predicting the activities of drug-metabolizing enzymes and drug transporters in individual patients.     

Converting an Esterase into an Epoxide Hydrolase

Entering the fold : A common structural motif in hydrolytic enzymes is the α,β‐hydrolase fold. The interconversion of one enzyme into another by introduction of mechanistically important residues is not enough; only substitution of a loop allows epoxide hydrolase activity in the esterase scaffold to be formed (see picture; structure comparison of epoxide hydrolases (green) with the esterase (orange)). The result is an enantioselective chimeric enzyme.

     

Preparation and evaluation of a chiral stationary phase covalently bound with a chiral pseudo-18-crown-6 ether having a phenolic hydroxy group for enantiomer separation of amino compounds

In order to develop a chiral stationary phase (CSP), which has even higher separation ability than the corresponding commercially available crown ether based CSP (OA-8000 having a pseudo-18-crown-6 ether with an OMe group as a selector), chemically bonded type CSP having a phenolic OH group on a crown ring was developed. Normal mobile phases with or without acid additive can be used with this OH type CSP in contrast to the conventional OMe type CSP which has a neutral chiral selector. Enantiomers of 25 out of 27 amino compounds, including 20 amino acids, 5 amino alcohols, and 2 lipophilic amines, were efficiently separated on a column with this CSP. Nine amino compounds out of 27 were separated with better separation factors than the corresponding OMe type CSP. It is noteworthy that the chromatography on this CSP exhibited excellent enantiomer-separations for amines and amino alcohols when triethyl amine was used as an additive in the mobile phase. Comparison of enantiomer separation ability on this OH type of CSP and on the OMe type of CSP and correlation between the enantioselectivity in chiral chromatography and that of the corresponding model compounds in solution imply that the chiral separation arose from chiral recognition in host guest interactions.