An access to the ß-anomer of 4'-thio-C-ribonucleosides: hydroboration of 1-C-aryl- or 1-C-heteroaryl-4-thiofuranoid glycals and its regiochemical outcome.

We have developed a novel method for the synthesis of the ß-anomer of 4'-thio-C-ribonucleosides from 3,5-O-(di-tert-butylsilylene)-4-thiofuranoid glycal. Palladium-catalyzed coupling of 1-tributylstannyl-4-thiofuranoid glycal with iodobenzene or a heteroaryl halide gave 1-C-phenyl- or 1-C-heteroaryl-glycals. Hydroboration of these glycals proceeded at the α-face, and subsequent alkaline hydrogen peroxide treatment of the resulting 2'-α-borane furnished the respective ß-anomer of 4'-thio-C-ribonucleosides. These results demonstrate that this synthetic method has a wider scope in terms of heterocyclic base structure. During this study, unexpected Markovnikov-oriented hydroboration has been observed to lead to the respective 1'-α-boranes. These 1'-boranes were converted into either the ring-opened structure or the 2'-deoxy derivatives depending upon their stability.

Evaluation of estrogen receptor Beta binding of pruni cortex and its constituents.

The bark of Prunus jamasakura Siebold (Pruni Cortex) has long been used in Japan as a folk remedy and is one of ingredients of the Kampo formula, Jumi-haidoku-to (JHT). JHT is used for treatment of skin diseases such as acne (acne vulgaris). According to Kampo medicinal sources, Quercus Cortex can be used in place of Pruni Cortex. In this study, we found that water extracts of Pruni Cortex, not Quercus Cortex showed a binding effect on estrogen receptor beta (ERbeta). Thus, their chemical analysis was carried out by GC-MS and found that five unique constituents (i.e., sakuranetin, naringenin, genistein, genkwanin and arctigenin) were detected in Pruni Cortex. The ERbeta binding capacity of these constituents was examined using 70 ng/ml 17beta-estradiol, as the positive control with 100% ERbeta binding. Among them, genistein (60% at 10 ng/ml) showed the strongest binding capacity than naringenin (60% at 1000 ng/ml) and sakuranetin (40% at 1000 ng/ml). These results suggested that Pruni Cortex in JHT could play an important role in treatment of acne. In addition, those of Pruni Cortex from different harvest places were also examined in their chemical contents and ERbeta binding capacity. The extracts of Pruni Cortex from Kyushu in Japan and Anhui Province in China showed higher contents of genistein and stronger ERbeta binding capacity than that of Pruni Cortex from Tokushima Prefecture in Japan.

Stereoselective synthesis of the beta-anomer of 4'-thionucleosides based on electrophilic glycosidation to 4-thiofuranoid glycals.

Three types of 4-thiofuranoid glycal with different 3,5-O-silyl protecting groups were prepared and their electrophilic glycosidation was investigated. The 3,5-bis-O-(tert-butyldimethylsilyl)-4-thiofuranoid glycal (5) was obtained through mesylation of 2-deoxy-4-thio-D-erythro-pentofuranose (4) and subsequent base-promoted elimination, while thermal elimination of sulfoxide derivatives was suitable for the preparation of 3,5-O-(tetraisopropyldisiloxane-1,3-diyl) (9) and 3,5-O-(di-tert-butylsilylene) (11) 4-thioglycals. The glycosidation reactions of these 4-thioglycals were carried out, in the presence of either PhSeCl or NIS, by using silylated derivatives of uracil, thymine, cytosine, and N(6)-benzoyladenine. Among the three 4-thioglycals, 11 was found to be an excellent glycosyl donor, forming the desired beta-anomer exclusively irrespective of the nucleobase employed.