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.

A novel method for determining peroxisomal fatty acid β-oxidation.

The purpose of this study is to establish an assay method to screen for chemical compounds that stimulate peroxisomal fatty acid β-oxidation activity in X-linked adrenoleukodystropy (X-ALD) fibroblasts. In this investigation, we used 12-(1-pyrene)dodecanoic acid (pyrene-C12:0), a fluorescent fatty acid analog, as a substrate for fatty acid β-oxidation. When human skin fibroblasts were incubated with pyrene-C12:0, β-oxidation products such as pyrene-C10:0 and pyrene-C8:0 were generated time-dependently.

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-Alzheimer's 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.

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.

Chemical cell-surface receptor engineering using affinity-guided, multivalent organocatalysts.

Catalysts hold promise as tools for chemical protein modification. However, the application of catalysts or catalyst-mediated reactions to proteins has only recently begun to be addressed, mainly in in vitro systems. By radically improving the affinity-guided DMAP (4-dimethylaminopyridine) (AGD) catalysts that we previously reported (Koshi, Y.