Concise synthesis of the CDE ring system of tetrahydroisoquinoline alkaloids using carbophilic Lewis acid-catalyzed hydroamidation and oxidative Friedel-Crafts cyclization

A concise synthesis of the CDE ring system of the tetrahydroisoquinoline antitumor alkaloids such as saframycins, renieramycins, and ecteinascidins has been developed. Both Au(I)-catalyzed intramolecular hydroamidation of alkynylamide and NBS-mediated oxidative Friedel-Crafts cyclization of the resulting 2-ketopiperazine were utilized as key reactions.     

Electron transfer activation of chromopyrrolic acid by cytochrome p450 en route to the formation of an antitumor indolocarbazole derivative: theory supports experiment

QM/MM calculations support experiment and show that StaP is a P450 that functions like a peroxidase: its active species is the one-electron-reduced Cpd II species with a radical on CPA, by analogy to cytochrome c peroxidase (CcP), and its reaction with the substrate proceeds by overall proton-coupled electron transfer (PCET), in analogy to the corresponding mechanism in horseradish peroxidase (HRP). The electron transfer is enabled by His250, the presence of carboxylate groups in CPA, and by the H-bonding network that tunes the energetic of the process. Theory supports experiment but reveals some novel aspects of this unusual P450.     

On the Singularity Structure of WKB Solution of the Boosted Whittaker Equation: its Relevance to Resurgent Functions with Essential Singularities

Inspired by the symbol calculus of linear differential operators of infinite order applied to the Borel transformed WKB solutions of simple-pole type equation [Kamimoto et al. (RIMS Kôkyûroku Bessatsu B 52:127–146, 2014)], which is summarized in Section 1, we introduce in Section 2 the space of simple resurgent functions depending on a parameter with an infra-exponential type growth order, and then we define the assigning operator \({\mathscr{A}}\) which acts on the space and produces resurgent functions with essential singularities. In Section 3, we apply the operator \({\mathscr{A}}\) to the Borel transforms of the Voros coefficient and its exponentiation for the Whittaker equation with a large parameter so that we may find the Borel transforms of the Voros coefficient and its exponentiation for the boosted Whittaker equation with a large parameter. In Section 4, we use these results to find the explicit form of the alien derivatives of the Borel transformed WKB solutions of the boosted Whittaker equation with a large parameter. The results in this paper manifest the importance of resurgent functions with essential singularities in developing the exact WKB analysis, the WKB analysis based on the resurgent function theory. It is also worth emphasizing that the concrete form of essential singularities we encounter is expressed by the linear differential operators of infinite order.     

Selective ultratrace detection of Al(III) and Ga(III) complexed with a calcein isomer by capillary zone electrophoresis with laser-induced fluorescence detection. Comparison of emissive polyaminocarboxylates as derivatizing ligands

A highly sensitive and selective capillary zone electrophoresis with laser-induced fluorescence detection (CZE-LIF) for Al(3+) and Ga(3+) was developed using a calcein 4',5'-isomer as a pre-capillary complexing agent. Direct fluorescent detection without an agent added to the carrier buffer provided the notable detection limits of 3.9x10(-10) and 4.6x10(-10)moldm(-3) for Al and Ga, respectively. By applying this system successfully to a river water sample, its potential for practical applications was ascertained. A comparison of three aromatic polyaminocarboxylate ligands related to the coordination structure and the distance between the fluorophore and the chelating moiety, revealed some interesting factors regarding their selectivity.     

Direct conversion to 2-phenyl-4-quinolones via a 4-alkoxyflavylium salt from a naturally occurring flavanone

A flavanone, in which a hydroxyl group at the 5-position was protected with a methyl group, converted to the corresponding 5-methoxy-2-phenyl-4-quinolone via flavylium salt under mild conditions. Flavanone-O-rhamnoglucoside, naringin, was also converted to 5-methoxy-2-phenyl-4-quinolon-7-O-rhamnoglucoside in the same way in an overall 25% yield.     

Charge‐discharge properties of composites of polypyrrole and vanadium oxide powder

Composite of polypyrrole and crystalline V₂O₅ powder was prepared by chemical oxidation of pyrrole with use of V₂O₅ powder itself as an oxidizing agent. The V₂O₅ content was changed from 0 to 94 wt% by changing the amount of V₂O₅ dispersed in the preparation bath. The pellet electrodes could be prepared by pressing the composite powder alone even if amount of polypyrrole in the composite was only 6 wt%. The resulting pellet electrode exhibited good charge‐discharge performance as a positive electrode of Li rechargeable battery in an electrolyte solution as well as in a quasi‐solid cell fabricated by using a gel electrolyte sheet of poly(methyl methacrylate).     

ELECT++: Faster conformational search method for docking flexible molecules using molecular similarity

We have developed a program, ELECT++ (Effective LEssening of Conformations by Template molecules in C++), to speed up the conformational search for small flexible molecules using the similar property principle. We apply this principle to molecular shape and, importantly, to molecular flexibility. After molecules in a database are clustered according to flexibility and shape (FCLUST++), additional reagents are generated to screen the conformational space of molecules in each cluster (TEMPLATE++). We call these representative reagents of each cluster template reagents. Template reagents and clustered reagents produce, after reaction, template molecules and clustered molecules, respectively (tREACT++). The conformations of a template molecule are searched in the context of a macromolecular target. Acceptable conformational choices are then applied to all molecules in its cluster, thus effectively biasing conformational space to speed up conformational searches (tSEARCH++). In our incremental search method, it is necessary to calculate the root-mean-square deviations (RMSD) matrix of distances between different conformations of the same molecule to reduce the number of conformations. Instead of calculating the RMSD matrix for all molecules in a cluster, the RMSD matrix of a template molecule is chosen as a reference and applied to all the molecules in its cluster. We demonstrate that FCLUST++ clusters the primary amine reagents from the Available Chemicals Directory (ACD) successfully. The program tSEARCH++ was applied to dihydrofolate reductase with virtual molecules generated by tREACT++ using clustered primary amine reagents. The conformational search by the program tSEARCH++ was about 4.8 times faster than by SEARCH++, with an acceptable range of errors. © 1998 John Wiley & Sons, Inc. J Comput Chem 19: 1834–1852, 1998     

K-Carrageenan Stimulates Pre-Osteoblast Proliferation and Osteogenic Differentiation: A Potential Factor for the Promotion of Bone Regeneration?

Current cell-based bone tissue regeneration strategies cannot cover large bone defects. K-carrageenan is a highly hydrophilic and biocompatible seaweed-derived sulfated polysaccharide, that has been proposed as a promising candidate for tissue engineering applications. Whether κ-carrageenan can be used to enhance bone regeneration is still unclear. In this study, we aimed to investigate whether κ-carrageenan has osteogenic potential by testing its effect on pre-osteoblast proliferation and osteogenic differentiation in vitro. Treatment with κ-carrageenan (0.5 and 2 mg/mL) increased both MC3T3-E1 pre-osteoblast adhesion and spreading at 1 h. K-carrageenan (0.125–2 mg/mL) dose-dependently increased pre-osteoblast proliferation and metabolic activity, with a maximum effect at 2 mg/mL at day three. K-carrageenan (0.5 and 2 mg/mL) increased osteogenic differentiation, as shown by enhanced alkaline phosphatase activity (1.8-fold increase at 2 mg/mL) at day four, and matrix mineralization (6.2-fold increase at 2 mg/mL) at day 21. K-carrageenan enhanced osteogenic gene expression (Opn, Dmp1, and Mepe) at day 14 and 21. In conclusion, κ-carrageenan promoted MC3T3-E1 pre-osteoblast adhesion and spreading, metabolic activity, proliferation, and osteogenic differentiation, suggesting that κ-carrageenan is a potential osteogenic inductive factor for clinical application to enhance bone regeneration.