Takashi Takahashi

We describe the design and synthesis of latex particles attached to an FR225659 derivative to identify its receptor proteins. Two key building blocks were prepared by two-step degradation of FR225659 under basic conditions. The designed ligand showed an acceptable level of biological activity to make it of potential value for use in affinity-supported receptor identification. Affinity purification of FR225659-binding proteins using the latex nanoparticles provided three candidate receptor peptides for the biological activity.

We describe an efficient solid-phase synthesis of clavulones via the sequential coupling of the alpha- and omega-chains, involving two separate carbon-carbon bond-forming steps. The tetrahydropyranyl linker survived these reaction conditions and was cleaved without decomposing the unstable cross-conjugated dienones. Our methodology has allowed us to prepare six clavulone derivatives that are varied within the alpha-chain.

We describe an efficient solid-phase synthesis of clavulones via the sequential coupling of the alpha- and omega-chains, involving two separate carbon-carbon bond-forming steps. The tetrahydropyranyl linker survived these reaction conditions and was cleaved without decomposing the unstable cross-conjugated dienones. Our methodology has allowed us to prepare six clavulone derivatives that are varied within the alpha-chain.

We describe the design and synthesis of alkylating reagents based on the structure of clavulones. They are composed of cross-conjugated dienone system and irreversibly reacted with two nucleophiles under mildly basic conditions via β-elimination. Hydroxyl derivative 7b showed the highest reactivity toward thiols and showed the strongest cytotoxicity in Hela S3 cells among the three derivatives having a different protecting group at the tert-hydroxyl group. © 2003 Elsevier Ltd. All rights reserved.

The reductive cyclization of epoxygeranyl acetate (1) was investigated using a catalytic amount of Cp2TiCl with various additives. The newly developed Cp2TiCl-Mn-lutidine·HCl-BEt3 system was found to be as effective as the reported stoichiometric system to afford the cyclized dehydro products 4 and 5 with 72% selectivity. © 2004 Elsevier Ltd. All rights reserved.

We describe the one-pot synthesis of core 2 class branched oligosaccharides initiated by chemo-selective glycosylation of silyl ether. Glycosylation of 6-O-silyl-4-benzyl-2-azido-thiogalactoside with glycosyl fluoride provided selectively 6-glycosylated thioglycoside without both O-glycosylation at the 3 position and S-glycosylation. Subsequent coupling of galactosyl fluoride and amino acids afforded the protected branched oligosaccharides in good yields. © 2003 Elsevier Ltd. All rights reserved.

We have successfully developed a synthetic strategy or the combinatorial solid-phase synthesis of carbohydrate clusters on a tree-type linker with two types of orthogonally cleavable parts. The combination of three types of spacers, two types of carbohydrate ligands, and two types of orthogonal cleavage provided a 12-member carbohydrate cluster library (6 dimers and 6 tetramers).

We have synthesized octa-, tetra-, and digalactoside based on the three methods of orthogonal cleavage (photo-, base, and acid cleavage) from the solid-supported tree-type linker with three types of orthogonally cleavable parts, simultaneously.

We describe the one-pot synthesis of core 2 class branched oligosaccharides initiated by chemo-selective glycosylation of silyl anther. Glycosylation of 6-O-silyl-4-benzyl-2-azido-thiogalactoside with glycosyl fluoride provided selectively 6-glycosylated thioglycoside without both O-glycosylation at the 3 position and S-glycosylation. Subsequent coupling of galactosyl fluoride and amino acids afforded the protected branched oligosaccharides in good yields. (C) 2003 Elsevier Ltd. All rights reserved.

The reductive cyclization of epoxygeranyl acetate (1) was investigated using a catalytic amount of Cp2TiCl with various additives. The newly developed Cp2TiCl-Mn-lutidine.HCl-BEt3 system was found to be as effective as the reported stoichiometric system to afford the cyclized dehydro products 4 and 5 with 72% selectivity. (C) 2004 Elsevier Ltd. All rights reserved.

We describe the design and synthesis of alkylating reagents based on the structure of clavulones. They are composed of cross-conjugated dienone system and irreversibly reacted with two nucleophiles under mildly basic conditions via beta-elimination. Hydroxyl derivative 7b showed the highest reactivity toward thiols and showed the strongest cytotoxicity in Hela S3 cells among the three derivatives having a different protecting group at the tert-hydroxyl group. (C) 2003 Elsevier Ltd. All rights reserved.

We describe an effective solid-phase synthesis of N-substituted naltrindoles using a nitro benzyl safety-catch linker. The linker is stable to both strongly acidic and basic conditions and is cleaved under mildly acidic conditions after conversion of the nitro group to an amide group. Using the linker, a combinatorial synthesis of N-substituted naltrindoles involving the Fischer indole synthesis and N-alkylation was accomplished to provide 16 N-substituted naltrindoles.

A liquid crystalline library of 100 molecules with three benzene rings and 18 molecules with two benzene rings was synthesized on solid support by means of benzoylation or acylation and palladium(0)-catalyzed carbonylation of a secondary amine obtained by a reductive amination of 4-iodoaniline and a backbone amide linker. The conversion and purity of the final products are high enough to investigate the mesomorphic properties. (C) 2003 Elsevier Ltd. All rights reserved.