Yasuaki Esumi

SYNTHETIC ASSEMBLY OF TRISACCHARIDE MOIETIES OF GLOBOTRIAOSYL CERAMIDE USING CARBOSILANE DENDRIMERS AS CORES. A NEW TYPE OF FUNCTIONAL GLYCO-MATERIAL

Abstract As a novel type of artificial receptor for Vero toxins, three pairs of carbosilane dendrimers uniformly carrying 12, 6, and 3 units of trisaccharide moieties of globotriaosyl ceramide were prepared through formation of the sulfide linkages in liquid NH3, which revealed unexpected differences among their biological responses.

Lucidenic acid O and lactone, new terpene inhibitors of eukaryotic DNA polymerases from a basidiomycete, Ganoderma lucidum

Terpenoids, 1, 2 and 3, which selectively inhibit eukaryotic DNA polymerase activities, were isolated from the fruiting body of a basidiomycete, Ganoderma lucidum, and their structures were determined by spectroscopic analyses. New terpenes, lucidenic acid O (1) and lucidenic lactone (2), prevented not only the activities of calf DNA polymerase alpha and rat DNA polymerase beta, but also these of human immunodeficiency virus type 1 reverse transcriptase. Cerevisterol (3), which was reported to be a cytotoxic steroid, inhibited only the activity of DNA polymerase alpha. Although these compounds did not influence the activities of prokaryotic DNA polymerases and other DNA metabolic enzymes such as T7 RNA polymerase and deoxyribonuclease I.

Isolation of 5-(8′Z-heptadecenyl)-resorcinol from etiolated rice seedlings as an antifungal agent

Abstract A new antifungal substance against rice blast fungus ( Pyricularia oryzae ), 5-(8′Z-heptadecenyl)resorcinol, was isolated from etiolated rice seedlings together with a mixture of its homologues with C 13 , C 15 , and C 17 saturated alkyl chains. Its structure was determined by 1 NMR, 13 C-NMR, and MS spectra. Its ED 50 was ca 40μg/ml. These 5-alkylresorcinols were newly produced after germination and the concentration reached 50 μg g −1 fresh weight on day 6.

An alternative route for the construction of carbosilane dendrimers uniformly functionalized with lactose or sialyllactose moieties

Abstract A new approach for the formation of an acetylthio linkage on aglycon by means of a radical addition of thioacetic acid into the CC double bond of the aglycon was examined. An introduction of a carbohydrate moiety into carbosilane dendrimers was demonstrated using a one-pot coupling reaction in MeOH–DMF in the presence of NaOMe via removal of an acetyl group of the acetylthio linkage in the saccharide moieties, producing a thiolate anion and a nucleophilic replacement of the thiolate to dendric alkyl bromide to form carbosilane dendrimers uniformly bearing lactose or sialyllactose moieties through thioether linkages in high yields.

Syntheses and biological evaluations of carbosilane dendrimers uniformly functionalized with sialyl α(2→3) lactose moieties as inhibitors for human influenza viruses ☆

A series of carbosilane dendrimers uniformly functionalized with sialyl lactose moieties (Neu5Ac alpha2-->3Gal beta1-->4Glc) was systematically synthesized, and biological evaluations for anti-influenza virus activity using the glycodendrimers were performed. The results suggested that the glycodendrimers had unique biological activities depending on the form of their core frame, and Dumbbell(1)6-amide type glycodendrimer 7 showed particularly strong inhibitory activities against human influenza viruses [A/PR/8/34 (H1N1) and A/Aichi/2/68 (H3N2)]. The results suggested that the structure-activity relationship (SAR) on the glycolibrary against various influenza viruses was observed, and dumbbell-shaped dendrimers as supporting carbohydrate moieties were found to be the most suitable core scaffolds in this study.

Systematic syntheses of influenza neuraminidase inhibitors: a series of carbosilane dendrimers uniformly functionalized with thioglycoside-type sialic acid moieties.

In order to develop novel influenza sialidase inhibitors, we constructed a library of glycoclusters composed of twelve types of sialylated dendrimers with thioglycosidic linkage that are resistant to hydrolysis by the sialidases. These sialodendrimers were synthesized by condensation reaction between a thiosialoside modified on the aglycon terminal end by a thioacetyl group and twelve types of carbosilane dendrimers having brominated terminal ends under deacetylation conditions, and temporal re-protection was performed for purification. Removal of all protection of the glycodendrimers was accomplished by transesterification and subsequent saponification to provide corresponding water-soluble glycodendrimers in good yields. For investigation of the structure-activity relationship, dendrimer scaffolds having differences in number of the sugar moieties, such as 3-, 4-, 6- and 12-functionalized dendrimers, and in linkage patterns, such as normal aliphatic linkage, ether- and amide-linkages. Biological evaluations of these glycodendrimers showed that all of the ether- and amide-elongated compounds had inhibitory potencies for the influenza sialidases in the mM range, while compounds having normal aliphatic linkage did not have any activities except for a 12-functionalized compound.

Metabolites of Pestalotiopsis spp., endophytic fungi of Taxus brevifolia

Abstract Two strains of Pestalotiopsis spp. (JCM 9685 and JCM 9686), endophytic fungi of Taxus brevifolia , produced several new compounds when grown in liquid culture. Detailed investigation on the first of these strains revealed that five of these metabolites were sesquiterpenes: three of the caryophyllene type, pestalotiopsin A, B and C, one possessing the humulane skeleton, and the last one was a drimane derivative. The remaining compounds were two C-methylated acetogenins: (4 S * ,5 R * )-(6 Z ,8 E )-4,5-dihydroxy-6-hydroxymethyl-6,8-decadiene and (4 S * ,5 R * )-(2 Z ,6 Z ,8E)-4,5-dihydroxy-6-hydroxymethyl-2,6,8-decatriene. Furthermore, an aldehyde closely related to these two triols was obtained from JCM 9686. The isolation and characterization of pestalotiopsin C and of the three new C-methylated acetogenins is described. The chemotaxonomic significance of the latter is discussed.

Vialinin A, a Novel 2,2-Diphenyl-1-picrylhydrazyl (DPPH) Radical Scavenger from an Edible Mushroom in China

While screening for bioactive compounds from edible mushrooms, a new potent antioxidant, vialinin A (1), together with a known compound, ganbajunin B (2), and a mixture of ganbajunins D (3) and E (4), were isolated from the dry fruiting bodies of Thelephora vialis. The structure of 1, 5′,6′-bis(phenylacetoxy)-1,1′:4′,1″-terphenyl-2′,3′,4,4″-tetraol, was elucidated by spectroscopic and chemical methods. This compound had strong 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical-scavenging activity with an EC50 value of 14.0 μM, nearly equal to that of butylated hydroxytoluene (BHT; EC50=10.0 μM). A radical scavenging experiment using 1 and DPPH radicals indicated that 1 donated two hydrogen atoms to two molecules of the DPPH radical under hydrophobic conditions.

Introduction of monosaccharides having functional groups onto a carbosilane dendrimer: A broadly applicable one-pot reaction in liquid ammonia involving Birch reduction and subsequent Sn2 reaction ☆

Benzylthioalkyl glycosides of D-glucuronic acid, N-acetyl-D-glucosamine, and N-acetylneuraminic acid (common monosaccharide constituents of natural oligosaccharide chains) have been prepared as sulfide precursors for the carbohydrate coating of dendric carbosilane cores and used in a generally applicable one-pot reaction (Birch reduction in liquid ammonia and subsequent SN2 reaction) to generate a thioether linkage between the monosaccharide moieties and a carbosilane dendrimer. The dendrimers were uniformly functionalized with the monosaccharides in good yields.

Sialyl α(2 → 3) lactose clusters using carbosilane dendrimer core scaffolds as influenza hemagglutinin blockers

An efficient synthesis of a series of carbosilane dendrimers uniformly functionalized with sialyl alpha(2-->3) lactose (Neu5Acalpha(2-->3)Galbeta(1-->4)Glcbeta1-->) moieties was accomplished. The results of a preliminary study on biological responses against influenza virus hemagglutinin, using the sialyl lactose clusters showed unique biological activities on the basis of the structure-activity relationship according to the carbosilane scaffolds.