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YAKUGAKU ZASSHI, 124(10),635-652, 2004
Dehydrative glycosidation reactions reported by the authors' group are reviewed. The authors' efforts were concentrated on developing reagent systems usable for one-stage-one-pot glycosidation. Such systems could simplify the glycosidation step using 1-OH sugar derivatives, since any preactivation stage for the hemiacetal OH group could be omitted. The systems, utilizing the dehydration potential of sulfonyl chloride, such as the p-nitrobenzenesulfonyl chloride-silver trifluoromethanesulfonate-triethylamine system as well as the p-nitrobenzenesulfonyl chloride-silver trifluoromethanesulfonate-N,N-dimethylacetamide-triethylamine system, were useful for the syntheses of many kinds of oligosaccharides. As a system free from any metals, the authors developed the trimethylsilyl trifluoromethanesulfonate-pyridine (TP) system. During the study of the system containing cobalt (II) bromide, the authors found that the bromide converts 1-OH sugar into the corresponding 1-Br derivative, which is then activated with the cobalt salt to undergo glycosidation with alcohol. To prepare partially benzylated sugar derivatives used as acceptors in the authors' studies, controlled benzylation and forced tritylation were carried out. Short syntheses of a variety of useful sugar derivatives using such convenient procedures are described. As a novel protecting group for the hemiacetal OH group, the authors used the 2-methoxyethyl group. Many kinds of trehalose-type disaccarides we prepared.
Key words--dehydrative glycosidation; 1-OH sugar derivative; partially benzylated sugars; trehalose; trehalosamine; macrolide sugars
YAKUGAKU ZASSHI, 124(10),653-666, 2004
Living bodies may experience oxidative stress induced by reactive oxygen species and heavy metal ions, which may damage components in the body and cause aging and disorders. In addition to the known defense systems against oxidative damage, the author describes new defense systems. Lipid peroxidation in living bodies, which has hitherto been thought to increase oxidative damage, was found to attenuate oxidative stress-induced DNA damage. Red blood cells become senescent due to oxidative stress during circulation, where membrane band 3 becomes aggregated to anti-band 3 IgG and macrophages attached through poly-N-acetyllactosaminyl sugar chains, and the sugar chain attachment to macrophages is stimulated by oxidative stress in macrophages. Oxidized protein hydrolase that preferentially hydrolyzes proteins damaged by oxidative stress was newly discovered, which may play an important role in saving cells from oxidative damage.
Key words--oxidative stress; lipid peroxidation; DNA damage; red blood cell aging; oxidized protein hydrolase
YAKUGAKU ZASSHI, 124(10),667-671, 2004
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a member of the vasoactive intestinal peptide (VIP)/secretin/ glucagon superfamily and functions as a hormone, neurohormone, and neurotransmitter in the central nervous system as well as in several peripheral tissues. Recently, several groups including ours have independently produced lines of mice lacking PACAP (PACAP−/−). These mutant mice have not only led to a better understanding of the physiologic roles of endogenous PACAP, but have also revealed some unexpected roles of PACAP. In this paper, phenotypic changes in several brain functions in PACAP−/− mice, including light-induced phase-resetting of the circadian activity rhythm, hippocampal long-term potentiation, and psychomotor behaviors, are reviewed based on the results obtained in our laboratory.
Key words--PACAP; neuropeptide; knockout mice; psychomotor behavior; circadian rhythm; long-term potentiation
YAKUGAKU ZASSHI, 124(10),673-681, 2004
Systematic synthesis of mono- and bis-THF ring cores, synthetic intermediates of antitumor annonaceous acetogenins, has been achieved by asymmetric alkynylation and subsequent stereodivergent THF ring formation as key steps. The asymmetric alkynylation of α-oxyaldehyde and α-tetrahydrofuranic aldehyde with (S)-3-butyne-1,2-diol derivatives gave good yield with very high diastereoselectivity. These adducts were converted into mono- and bis-THF cores via two kinds of one-pot THF ring formation, respectively. In addition, the total synthesis of murisolin, which shows cytotoxic activity against human tumor cell lines with potency from 105 to 106 times that of adriamycin, was also achieved.
Key words--annonaceous acetogenins; systematic synthesis; tetrahydrofuran ring formation; antitumor agent; asymmetric alkynylation
YAKUGAKU ZASSHI, 124(10),683-692, 2004
The spontaneously hypertensive rat (stroke-prone) (SHRSP) experiences severe hypertension and cerebral hemorrhage. The serum cholesterol level in this rat is lower than that in the normotensive Wistar-Kyoto rat. Epidemiologic studies have indicated a negative association between serum cholesterol level and the incidence of cerebral hemorrhage in humans. Therefore the low level of serum cholesterol in SHRSP may cause cerebral strokes. The following investigation demonstrated that the activity for the biosynthesis of cholesterol is decreased in SHRSP due to the reduced activity of mevalonate pyrophosphate decarboxylase (MPD). However, the mechanism underlying the reduced activity of this enzyme remains unclear. In this review, we indicate that the level of MPD in the brain and liver of SHRSP is reduced from the age of 2 weeks.
Key words--Mevalonate pyrophosphate decarboxylase, SHRSP, WKY, liver, brain
YAKUGAKU ZASSHI, 124(10),693-697, 2004
Due to the evolvement of the aged society and the steep rise in medical costs, the environment encircling the medical care industry has been changing remarkably. For this reason, it has become both necessary and fundamental for a community pharmacist to participate in home medical care through the pharmaceutical management service. We have studied the associated costs and medical service fees for pharmaceutical management in home medical care. The costs and medical service fees were calculated based on the pharmaceutical management service data collected during the three years from November 1998 to October 2001. As a result, the medical service fees were calculated using the old system which lasted until March 2002. Calculations using this system took into account 550 points per visit, up to two visits per month. Under the new system which started in April 2002, the number of visits taken into account is four times a month, 500 points for the first visit, 300 points from the second through to the forth visit. Then, we simulated a break-even point (BEP). It is clear that it is difficult for any community pharmacy to be specialized in home medical care. In order for the pharmacist to actively participate in home medical care in the future, it is necessary to further improve the system.
Key words--home medical care; medical service fee; aged society; cost
YAKUGAKU ZASSHI, 124(10),699-703, 2004
Photobacterium leiognathi cultured in marine broth emits a luminescence that is temporarily enhanced and then extinguished by glucose. Glucose reduces the luciferase level and the expression of lux ABG mRNA in P. leiognathi. The amount of ATP in P. leiognathi is temporarily increased and then declines to the normal level. These results indicate that the extinguishing by glucose in P. leiognathi is induced by the interruption of the translation of luciferase.
Key words--Photobacterium leiognathi; glucose; luciferase
YAKUGAKU ZASSHI, 124(10),705-709, 2004
Licorice, Glycyrrhiza glabra Linn., is one of herbal medicines widely used for various purposes, including as a sweetener and for gastric ulcer treatment. However, environmental destruction due to the harvesting of wild licorice is becoming a serious problem. We cultured licorice in a hydroponic system to examine the relation between the concentration of nutritional solution applied and glycyrrhizin content to determine the optimal nutrient solution concentration for commercial licorice production. Licorice growth and glycyrrhizin content in the root reached the highest values when the plants received nutrient solution approximately equivalent to a quarter unit of Hoagland solution. The results also indicated that the glycyrrhizin content does not correlate with the concentration of nutrient solution applied and/or inorganic contents absorbed, i.e., licorice may absorb large amounts of nutrient solution but the glycyrrhizin content may not increase.
Key words--herbal medicine; Glycyrrhiza glabra; nutrient requirement; commercial production; glycyrrhizin accumulation