Preparation,crystal structure,and spectroscopic,chemical, and electrochemical properties of (2E,4E)-1,4-di(3-guaiazulenyl)-1,3-butadiene compared with those of (E)-1,2-di(3-guaiazulenyl)ethylene

Wittig reaction of (E)-3-(3-guaiazulenyl)propenal (11) with (3-guaiazulenylmethyl)triphenylphosphonium bromide (9) in ethanol containing NaOEt at 25 °C for 24 h under argon gives the title new (2E,4E)-1,3-butadiene derivative 4, in 33% isolated yield, which upon treatment with hexafluorophosphoric acid (i.e., 65% HPF₆ aqueous solution) in tetrahydrofuran (=THF) at 25 °C for 1 h under aerobic conditions affords a new air (two-electron) oxidation product (E)-ethylene-1,2-bis(3-guaiazulenylmethylium) bis(hexafluorophosphate) (14), quantitatively, and further, zinc-reduction of 14 in trifluoroacetic acid (=CF₃COOH) at 0 °C for 1 h under argon reverts 4, quantitatively. Along with the above interesting results, our discovered another preparation method, spectroscopic properties, crystal structure, and electrochemical behavior of 4, which serves as a strong two-electron donor and acceptor, compared with those of the previously reported (E)-1,2-di(3-guaiazulenyl)ethylene (3) are documented in detail.     

Mechanism of the alkali degradation of (6-4) photoproduct-containing DNA

The (6-4) photoproduct is one of the major damaged bases produced by ultraviolet light in DNA. This lesion is known to be alkali-labile, and strand breaks occur at its sites when UV-irradiated DNA is treated with hot alkali. We have analyzed the product obtained by the alkali treatment of a dinucleoside monophosphate containing the (6-4) photoproduct, by HPLC, NMR spectroscopy, and mass spectrometry. We previously found that the N3-C4 bond of the 5' component was hydrolyzed by a mild alkali treatment, and the present study revealed that the following reaction was the hydrolysis of the glycosidic bond at the 3' component. The sugar moiety of this component was lost, even when a 3'-flanking nucleotide was not present. Glycosidic bond hydrolysis was also observed for a dimer and a trimer containing 5-methyl-2-pyrimidinone, which was used as an analog of the 3' component of the (6-4) photoproduct, and its mechanism was elucidated. Finally, the alkali treatment of a tetramer, d(GT(6-4)TC), yielded 2'-deoxycytidine 5'-monophosphate, while 2'-deoxyguanosine 3'-monophosphate was not detected. This result demonstrated the hydrolysis of the glycosidic bond at the 3' component of the (6-4) photoproduct and the subsequent strand break by β-elimination. It was also shown that the glycosidic bond at the 3' component of the Dewar valence isomer was more alkali-labile than that of the (6-4) photoproduct.     

Synthesis and pharmacological evaluation of 3-amino-1-(5-indanyloxy)-2-propanol derivatives as potent sodium channel blockers for the treatment of stroke

In investigating potent sodium (Na(+)) channel blockers for the treatment of ischemic stroke, we synthesized a novel series of 3-amino-1-(5-indanyloxy)-2-propanol derivatives and evaluated their inhibitory effects on neuronal Na(+) channels. The 3-amino-1-(5-indanyloxy)-2-propanol derivatives exhibited potent blocking activity for Na(+) channels and a significantly low affinity for dopamine D(2) receptors, which demonstrates a minimal clinical risk for extrapyramidal side effects. In particular, compound 4b, a 3-amino-1-(5-indanyloxy)-2-propanol derivative bearing a benzimidazole moiety, showed desirable neuroprotective activity in a rat transient middle cerebral artery occlusion model. Furthermore, compound 4b displayed a high binding affinity for neurotoxin receptor site 2 of the Na(+) channels, which suggests that 4b would act as a use-dependent Na(+) channel blocker in sustained depolarization during ischemic stroke.     

Sooner and Later Waiting Time Problems Based on a Dependent Sequence

This paper introduces a new concept: a binary sequence of order (k,r), which is an extension of a binary sequence of order k and a Markov dependent sequence. The probability functions of the sooner and later waiting time random variables are derived in the binary sequence of order (k,r). The probability generating functions of the sooner and later waiting time distributions are also obtained. Extensions of these results to binary sequence of order (g,h) are also presented.     

Discrete distributions of orderk on a binary sequence

Summary This paper considers discrete distributions of orderk based on a binary sequence which is defined as an extension of independent trials with a constant success probability and is more practical than the independent trials. Some results on calculation of probabilities and characteristics of the distributions are obtained as well as their formal expressions. Examples and an application are also given. The Institute of Statistical Mathematics     

Joint Distributions of Numbers of Runs of Specified Lengths in a Sequence of Markov Dependent Multistate Trials

Let Z ₀, Z ₁,...,Z _n be a sequence of Markov dependent trials with state space Ω = {F ₁,...,F _λ, S ₁,...,S _ν}, where we regard F ₁,...,F _λ as failures and S ₁,...,S _ν as successes. In this paper, we study the joint distribution of the numbers of S _i -runs of lengths k _ij (i = 1,2,...,ν, j = 1,2,...,r _i ) based on four different enumeration schemes. We present formulae for the evaluation of the probability generating functions and the higher order moments of this distribution. In addition, when the underlying sequence is i.i.d. trials, the conditional distribution of the same run statistics, given the numbers of success and failure is investigated. We give further insights into the multivariate run-related problems arising from a sequence of the multistate trials. Besides, our results have potential applications to problems of various research areas and will come to prominence in the future. This research was partially supported by the ISM Cooperative Research Program (2004-ISM·CRP-2007).     

Some test statistics based on the martingale term of the empirical distribution function

Summary It is proved that the martingale term of the empirical distribution function converges weakly to a Gaussian process inD[0, 1]. Some statistics for goodness-of-fit tests based on the martingale term of the empirical distribution function are proposed. Asymptotic distributions of these statistics under the null hypothesis are given. The approximate Bahadur efficiencies of the statistics to the Kolmogorov-Smirnov statistic and to the Cramér-von Mises statistic are also calculated. The Institute of Statistical Mathematics     

Ni- or Cu-catalyzed cross-coupling reaction of alkyl fluorides with Grignard reagents

n-Octyl fluoride underwent a cross-coupling reaction with n-propylmagnesium bromide in the presence of 1,3-butadiene using NiCl2 as a catalyst at room temperature to give undecane in moderate yields. This alkyl-alkyl cross-coupling proceeded more efficiently when CuCl2 was employed instead of NiCl2. Addition of 1,3-butadiene dramatically improved the yields of the coupling products from primary alkyl Grignard reagents in both Ni- and Cu-catalyzed reactions. Alkyl fluorides efficiently reacted with tertiary alkyl and phenyl Grignard reagents using CuCl2 in the absence of 1,3-butadiene to afford the coupling products in high yields. The competitive reaction of a mixture of alkyl halides (R-X; X = F, Cl, Br) with nC5H11MgBr showed that the reactivities of the halides increase in the order R-Cl < R-F < R-Br. In contrast, in the Cu-catalyzed reaction with PhMgBr, the reactivities increase in the order R-Cl < R-Br < R-F.