Daishiro Minato

Synthesis of Denosomin–Vitamin D3 Hybrids and Evaluation of Their Anti-Alzheimer’s Disease Activities

As an extension of previously conducted studies on developing an anti-Alzheimers disease agent, denosomin (1-deoxy-24-norsominone, an artificial inducer of neurite elongation), derivatives were designed and synthesized based on the hypothesis that our denosomin would exhibit axonal extension activity via a 1,25D(3)-membrane-associated, rapid response steroid-binding protein (1,25D(3)-MARRS) pathway. The biological assay revealed that the hybridization of characteristic δ-lactone in denosomin and the triene moiety in VD(3) was effective to enhance the nerve re-extension activity in amyloid β (Aβ)-damaged neurons.

Highly Efficient Access to Both Geometric Isomers of Silyl Enol Ethers: Sequential 1,2-Brook/Wittig Reactions

Novel sequential 1,2-Brook/Wittig reactions were developed for the preparation of silyl enol ethers. This method enables highly selective preparation of both geometric isomers of glyoxylate silyl enol ethers, using aldehydes (E-selective) and tosylimines (Z-selective) as a Wittig electrophile. The salt-free conditions of this reaction system are likely to be advantageous for switching the selectivity. The optimal reaction conditions and generality of the reaction were investigated, and plausible explanations for the observed selectivity were also discussed.

Synthesis and biological evaluation of N-(2-fluorophenyl)-2β-deoxyfuconojirimycin acetamide as a potent inhibitor for α-l-fucosidases.

In this study we revealed that the addition of an N-phenylacetamide substituent to the C-1 position of 1-deoxyfuconojirimycin (DFJ) can lead to highly potent inhibitors of α-l-fucosidases. A structure-activity relationship study showed that a fluoro group on the phenyl ring greatly increased its potency and selectivity. In contrast the addition of two or three fluoro groups decreased their inhibition potency. Consequently, N-(2-fluorophenyl)-2β-DFJ acetamide (18j) was found to display very potent and selective inhibition of bovine kidney, rat epididymis, and human lysosome α-l-fucosidases, with IC50 value of 0.012, 0.044, and 0.0079μM respectively. It is noteworthy that our designed N-phenyl-2β-DFJ acetamide derivative exhibited about 18-fold stronger effects on human lysosomal α-l-fucosidase than original DFJ and it occupied the active-site of this enzyme. We therefore expect that this compound may find applications in new therapeutic trials against genetic deficiency disorders.

Construction of cis-Fused Hydrindane Skeleton with a Lactone Tether Utilizing Intramolecular Diels-Alder Reaction

Construction of cis-fused hydrindane skeleton with a lactone tether utilizing intramolecular Diels-Alder reaction Shuqing Yin, Kenji Takai, Daishiro Minato, Kenji Sugimoto, Hideki Ohtsu, Kiyoshi Tsuge, and Yuji Matsuya* Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan, Graduate School of Science and Engineering, University of Toyama, 3190 Gofuku, Toyama 930-8555, Japan.