Preparation of 3-bromo-2-methylfuran and 4-bromo-2-methylfuran

4-endo-5-exo-Dibromo-3-methyl-3,6-endo-oxyperhydrophthalic anhydride 3b and 4-exo-5-endo-dibro-mo-3-methyl-3,6-endo-oxyperhydrophtbalic anhydride 3c were isolated from the bromo-adducts of 3-methyl-3,6-endo-oxy-1,2,3,6-tetrahydrophthalic anhydride 2. When 3b or 3c was heated in quinoline, only 3-bromo-2-methylfuran 4 was obtained from 3b and only 4-bromo-2-methylfuran 5 from 3c.     

Tubiferal A, a backbone-rearranged triterpenoid lactone isolated from the myxomycete Tubifera dimorphotheca, possessing reversal of drug resistance activity

Tubiferal A, a novel rearranged triterpenoid lactone, has been isolated from field-collected fruit bodies of the myxomycete, Tubifera dimorphotheca, and its structure elucidated by spectral data. Tubiferal A (1) possesses a 9,10-secocycloartan-16,21-olide skeleton, and this new compound exhibited a reversal effect of vincristine (VCR) resistance (more than 4-fold) against VCR-resistant KB cell lines. Tubiferal B (2), corresponding to the seco acid of 1 was also isolated, but showed no comparable activity.     

Preparation of 5,5-dicyano- and 5-cyano-5-ethoxycarbonyl-5,6-dihydro-3,7-diphenyl-4H-1,2-diazepines and their halogenations

5,5-Dicyano- and 5-cyano-5-ethoxycarbonyl-5,6-dihydro-3,7-diphenyl-4H-1,2-diazepines were prepared by the condensation of α-bromoacetophenone azine with malononitrile and ethyl cyanoacetate in the presence of sodium ethoxide, respectively. Halogenations of the dihydrodiazepines gave pyridazines, diazanorcaradienes, 4,4,6,6-tetrachlorodihydrodiazepines, and/or a 4-chloropyrazole whose relative yields strongly depended upon the nature of 5-substituents of the dihydrodiazepines as well as the reaction conditions.     

Synthesis and evaluation of novel pyrimido-acridone, -phenoxadine, and -carbazole as topoisomerase II inhibitors

As part of a series of studies to discover new topoisomerase II inhibitors, novel pyrimidoacridones, pyrimidophenoxadines, and pyrimidocarbazoles were synthesized, and in vitro and in vivo antitumor activities and DNA-protein and/or DNA-topoisomerase II cross-linking activity as an indicator of topoisomerase II-DNA cleavable complex formation were evaluated. The pyrimidocarbazoles possessed high in vitro and in vivo potencies. Compound 26 (ER-37326), 8-acetyl-2-[2-(dimethylamino)ethyl]-1H-pyrimido[5,6,1-jk]carbazole-1,3(2H)-dione, showed in vitro growth inhibitory activity with respective IC(50) values of 0.049 microM and 0.35 microM against mouse leukemia P388 and human oral cancer KB. In vivo, this compound inhibited the tumor growth of mouse sarcoma M5076 implanted into mice with T/C values of 42% and 13% at 3.13 and 6.25 mg/kg/d respectively without significantly affecting the body weight. In addition, compound 26 (ER-37326) increased the formation of DNA-topoisomerase II cross-linking in P388 cells.     

Heterogeneously catalyzed aerobic oxidative biaryl coupling of 2-naphthols and substituted phenols in water

The oxidative coupling reaction can efficiently be promoted by supported ruthenium catalyst Ru(OH)x/Al2O3. A variety of 2-naphthols and substituted phenols can be converted to the corresponding biaryl compounds in moderate to excellent yields using molecular oxygen as a sole oxidant in water without any additives. The catalysis is truly heterogeneous in nature, and Ru(OH)x/Al2O3 can easily be recovered after the reaction. The catalyst can be recycled seven times with the maintenance of the catalytic performance, and the total turnover number reaches up to 160. The results of competitive coupling reactions suggest that the present oxidative biaryl coupling reaction proceeds via the homolytic coupling of two radical species and the Ru(OH)x/Al2O3 catalyst acts as an one-electron oxidant. Two radical species are coupled to give the corresponding biaryl product, and the one-electron reduced catalyst is reoxidized by molecular oxygen. The amounts of O(2) uptake and H(2)O formation were almost one-quarter and one-half the amount of substrate consumed, respectively, supporting the reaction mechanism. The kinetic data and kinetic isotope effect show that the reoxidation of the reduced catalyst is the rate-limiting step for the coupling reaction.     

High-performance liquid chromatographic detector based on near-infrared semiconductor laser fluorimetry

Three polymethine dyes, which fluoresce at 780–820 nm, are separated by reversed-phase chromatography and detected fluorimetrically with a semiconductor laser for excitation. The detection limit for anhydro-3,3,3′,3′-tetramethyl-1,1′-bis(4-sulfomethyl)-4,5,4′,5′-dibenzoindotricarbocyanine hydroxide (sodium salt) is 0.3 pg, which is almost three orders of magnitude better than the value obtained by conventional fluorimetry.     

Stochastic equations on compact groups in discrete negative time

In this paper a stochastic equation on compact groups in discrete negative time is studied. The diagonal group action on the extreme points of solutions is proved to be transitive by means of the coupling method. This result is applied to generalize Yor’s work which is closely related to Tsirelson’s stochastic differential equation and to give criteria for existence of a strong solution and for uniqueness in law. This research was supported by Open Research Center Project for Private Universities: matching fund subsidy from MEXT, 2004–2008.