高橋 孝志

Synthesis of beauveriolide III (1b), which is an inhibitor of lipid droplet accumulation in macrophages, was achieved by solid-phase assembly of linear depsipeptide using a 2-chlorotrityl linker followed by solutionphase cyclization. On the basis of this strategy, a combinatorial library of beauveriolide analogues was carried out by radio frequency-encoded combinatorial chemistry. After automated purification using preparative reversed-phase HPLC, the library was tested for inhibitory activity of CE synthesis in macrophages to determine structure-activity relationships of beauveriolides. Among them, we found that diphenyl derivative 7{9,1} is 10 times more potent than 1b.

Two chiral bent-core mesogens Pn-O-PIMB(n - 2)* (n = 9 and 10) and their oxygen analogues Pn-O-PIMB(n - 2)*-(n - 4)0 (n = 8, 9, and 10) with omega-[(S)-amyloxy]alkoxy terminal groups were prepared, and their phase structures were investigated by means of electro-optic, polarization reversal current and second harmonic generation measurements in order to clarify the effect of the interlayer steric interaction on the emergence of polar orderings. The odd-even behavior for the alternative appearance of ferroelectricity and antiferroelectricity was observed in two homologous series; the bent-core mesogens P10-O-PIMB8*, P8-O-PIMB6*-4O, and P10-O-PIMB8*-6O in addition to the previously reported P6-O-PIMB4* and P8-O-PIMB6*, where the length of chains n is even, exhibited ferroelectric phases. On the contrary, the mesogens P7-O-PIMB5*, P9-O-PIMB7*, and P9-O-PIMB7*-5O, where n is odd, showed antiferroelectric phases. It is obvious that the interlayer steric interaction plays a major role for the emergence of a variety of phase structures.

Two chiral bent-core mesogens Pn-O-PIMB(n - 2)* (n = 9 and 10) and their oxygen analogues Pn-O-PIMB(n - 2)*-(n - 4)0 (n = 8, 9, and 10) with omega-[(S)-amyloxy]alkoxy terminal groups were prepared, and their phase structures were investigated by means of electro-optic, polarization reversal current and second harmonic generation measurements in order to clarify the effect of the interlayer steric interaction on the emergence of polar orderings. The odd-even behavior for the alternative appearance of ferroelectricity and antiferroelectricity was observed in two homologous series; the bent-core mesogens P10-O-PIMB8*, P8-O-PIMB6*-4O, and P10-O-PIMB8*-6O in addition to the previously reported P6-O-PIMB4* and P8-O-PIMB6*, where the length of chains n is even, exhibited ferroelectric phases. On the contrary, the mesogens P7-O-PIMB5*, P9-O-PIMB7*, and P9-O-PIMB7*-5O, where n is odd, showed antiferroelectric phases. It is obvious that the interlayer steric interaction plays a major role for the emergence of a variety of phase structures.

An effective method for the synthesis of aryl hydrazines by amination of anilines using the solid-supported phenylsufonyl-hydroxylamine was described. Treatment of aniline with the solid-supported aminating agent, followed by removal of the resin, provided the corresponding hydrazine in 21% yield. The resulting hydrazines were directly adapted to the solid-phase synthesis of indoles, providing nine naltrindole derivatives varying the substituents on the aromatic rings.

We have developed a practical synthetic route to construct C-aromatic taxane derivatives as three-dimension templates by way of intramolecular alkylation. The usefulness of synthesized compounds as the core template was evaluated by using a newly developed screening system for P-glycoprotein. (c) 2005 Elsevier Ltd. All rights reserved.

An effective method for the synthesis of aryl hydrazines by amination of anilines using the solid-supported phenylsufonyl-hydroxylamine was described. Treatment of aniline with the solid-supported aminating agent, followed by removal of the resin, provided the corresponding hydrazine in 21% yield. The resulting hydrazines were directly adapted to the solid-phase synthesis of indoles, providing nine naltrindole derivatives varying the substituents on the aromatic rings.

We have developed a practical synthetic route to construct C-aromatic taxane derivatives as three-dimension templates by way of intramolecular alkylation. The usefulness of synthesized compounds as the core template was evaluated by using a newly developed screening system for P-glycoprotein. (c) 2005 Elsevier Ltd. All rights reserved.

We describe an efficient synthesis of H type 1 and 2 trisaccharides by one-pot glycosylation involving glycosidation of glycal epoxide. Copyright © 2005 The Chemical Society of Japan.

We describe an efficient synthesis of H type 1 and 2 trisaccharides by one-pot glycosylation involving glycosidation of glycal epoxide. Copyright © 2005 The Chemical Society of Japan.

An efficient synthesis of a protected dimeric Lewis X epitope by two sequential one-pot glycosylations is described. Combinatorial synthesis of the dimeric Lewis X epitope derivatives by the one-pot glycosylation was accomplished utilizing an automated synthesizer to provide 12-protected oligosaccharides.

The stereoselective formation of the C ring was accomplished by nitrile oxide [3+2] cycloaddition of an intermediate with the A ring already constructed. We found that stereoelectronic effect to a 1,1-substituted alkene moiety is important in the reaction.

1,3-Dipolar cycloaddition of azomethine imines to the polymer-supported vinylsulfone was achieved. Pyrazole derivatives bearing various aryl groups were synthesized regioselectively.

New unsymmetrical banana-shaped molecular series having C different lengths of alkyl flexible chain on both side wings designated by "P-(n(1), n(2))-OPIMB", are studied comparing with the symmetric banana molecules in P-n-O-PIMB homologues.

An efficient synthesis of a protected dimeric Lewis X epitope by two sequential one-pot glycosylations is described. Combinatorial synthesis of the dimeric Lewis X epitope derivatives by the one-pot glycosylation was accomplished utilizing an automated synthesizer to provide 12-protected oligosaccharides.

The stereoselective formation of the C ring was accomplished by nitrile oxide [3+2] cycloaddition of an intermediate with the A ring already constructed. We found that stereoelectronic effect to a 1,1-substituted alkene moiety is important in the reaction.

1,3-Dipolar cycloaddition of azomethine imines to the polymer-supported vinylsulfone was achieved. Pyrazole derivatives bearing various aryl groups were synthesized regioselectively.

New unsymmetrical banana-shaped molecular series having C different lengths of alkyl flexible chain on both side wings designated by "P-(n(1), n(2))-OPIMB", are studied comparing with the symmetric banana molecules in P-n-O-PIMB homologues.

The efficient and elegant synthesis of N-glycosides by N-glycosylation of asparagine-containing peptides is described. Glycosylation of primary amides with glycosyl N-phenyltrifluoroimidates in the presence of a catalytic amount of TMSOTf in nitromethane smoothly proceeded to provide the corresponding N-glycosyl amino acids in excellent yields. This coupling method was adaptable to the coupling of various glycosyl donors with amino acids and peptides. Copyright © 2005 American Chemical Society.

The Asp-Thr tethered Diels-Alder reaction of 1a was accomplished to provide 2a exclusively in a regio- and stereoselective manner.

The Asp-Thr tethered Diels-Alder reaction of 1a was accomplished to provide 2a exclusively in a regio- and stereoselective manner.

The synthesis of two latex nano-particles coupled to FR901464 derivatives is described. Two FR901464 derivatives attached with an amino-alkyl group at a different position were prepared from natural occurring FR 901464. Biological activities of the two ligands were significantly different. The acylation of two amino ligands with the activated esters on latex particles smoothly proceeded to provide the corresponding latex nano-particles coupled to FR 901464 at a different position.

The synthesis of two latex nano-particles coupled to FR901464 derivatives is described. Two FR901464 derivatives attached with an amino-alkyl group at a different position were prepared from natural occurring FR 901464. Biological activities of the two ligands were significantly different. The acylation of two amino ligands with the activated esters on latex particles smoothly proceeded to provide the corresponding latex nano-particles coupled to FR 901464 at a different position.

Novel derivative series of the well known bent-shaped P-n-O-PIMB liquid crystal mesogens, referred to as '4Br-P-n-O-PIMB', '4Cl-P-N-O-PIMB' and '5Cl-P-n-O-PIMB', having halogen atoms substituted on the phenyl ring in the central core, were synthesized by solution phase parallel synthesis based on a combinatorial approach. The mesomorphic behaviour and physical properties of all the new compounds were studied by means of optical microscopy, differential scanning calorimetry, X-ray and circular dichroism spectroscopy. We found interesting transitional behaviour for the 4Br-P-n-O-PIMB homologous series. The homologues with alkyl tails having carbon numbers of n=3-10, 12, 14 exhibit rather complicated mesomorphic behaviour, which is strongly sensitive to n. The chiral fluid smectic B2 phase with SmCAPA structure and unidentified smectic Bx phase were observed in the homologues with n = 9, 10, 12, 14 and n=3-5, respectively. Interestingly, every member exhibits frustrated and/or helical ordered phases at low temperatures, designated as X1, X2, and X3 phases, which result from a spontaneous escape from a macroscopic polarization. The mesomorphic behaviour and mesophase structures differ remarkably from those of the parent P-n-O-PIMB homologues, suggesting that substitution of the halogen atoms at the central core essentially creates a particular interaction between molecules.

Novel derivative series of the well known bent-shaped P-n-O-PIMB liquid crystal mesogens, referred to as '4Br-P-n-O-PIMB', '4Cl-P-N-O-PIMB' and '5Cl-P-n-O-PIMB', having halogen atoms substituted on the phenyl ring in the central core, were synthesized by solution phase parallel synthesis based on a combinatorial approach. The mesomorphic behaviour and physical properties of all the new compounds were studied by means of optical microscopy, differential scanning calorimetry, X-ray and circular dichroism spectroscopy. We found interesting transitional behaviour for the 4Br-P-n-O-PIMB homologous series. The homologues with alkyl tails having carbon numbers of n=3-10, 12, 14 exhibit rather complicated mesomorphic behaviour, which is strongly sensitive to n. The chiral fluid smectic B2 phase with SmCAPA structure and unidentified smectic Bx phase were observed in the homologues with n = 9, 10, 12, 14 and n=3-5, respectively. Interestingly, every member exhibits frustrated and/or helical ordered phases at low temperatures, designated as X1, X2, and X3 phases, which result from a spontaneous escape from a macroscopic polarization. The mesomorphic behaviour and mesophase structures differ remarkably from those of the parent P-n-O-PIMB homologues, suggesting that substitution of the halogen atoms at the central core essentially creates a particular interaction between molecules.

Novel derivative series of the well known bent-shaped P-n-O-PIMB liquid crystal mesogens, referred to as '4Br-P-n-O-PIMB', '4Cl-P-n-O-PIMB' and '5Cl-P-n-O-PIMB', having halogen atoms substituted on the phenyl ring in the central core, were synthesized by solution phase parallel synthesis based on a combinatorial approach. The mesomorphic behaviour and physical properties of all the new compounds were studied by means of optical microscopy, differential scanning calorimetry, X-ray and circular dichroism spectroscopy. We found interesting transitional behaviour for the 4Br-P-n-O-PIMB homologous series. The homologues with alkyl tails having carbon numbers of n=3-10, 12, 14 exhibit rather complicated mesomorphic behaviour, which is strongly sensitive to n. The chiral fluid smectic B2 phase with SmCAPA structure and unidentified smectic Bx phase were observed in the homologues with n=9, 10, 12, 14 and n=3-5, respectively. Interestingly, every member exhibits frustrated and/or helical ordered phases at low temperatures, designated as X1, X2, and X3 phases, which result from a spontaneous escape from a macroscopic polarization. The mesomorphic behaviour and mesophase structures differ remarkably from those of the parent P-n-O-PIMB homologues, suggesting that substitution of the halogen atoms at the central core essentially creates a particular interaction between molecules.

Novel derivative series of the well known bent-shaped P-n-O-PIMB liquid crystal mesogens, referred to as '4Br-P-n-O-PIMB', '4Cl-P-n-O-PIMB' and '5Cl-P-n-O-PIMB', having halogen atoms substituted on the phenyl ring in the central core, were synthesized by solution phase parallel synthesis based on a combinatorial approach. The mesomorphic behaviour and physical properties of all the new compounds were studied by means of optical microscopy, differential scanning calorimetry, X-ray and circular dichroism spectroscopy. We found interesting transitional behaviour for the 4Br-P-n-O-PIMB homologous series. The homologues with alkyl tails having carbon numbers of n=3-10, 12, 14 exhibit rather complicated mesomorphic behaviour, which is strongly sensitive to n. The chiral fluid smectic B2 phase with SmCAPA structure and unidentified smectic Bx phase were observed in the homologues with n=9, 10, 12, 14 and n=3-5, respectively. Interestingly, every member exhibits frustrated and/or helical ordered phases at low temperatures, designated as X1, X2, and X3 phases, which result from a spontaneous escape from a macroscopic polarization. The mesomorphic behaviour and mesophase structures differ remarkably from those of the parent P-n-O-PIMB homologues, suggesting that substitution of the halogen atoms at the central core essentially creates a particular interaction between molecules.

Catch and release method utilizing polymer-support was investigated in the separation of 1alpha,25-(OH)(2) pre- and provitamin D-3. Polymer-supported alkyldiisopropylsityl triflate selectively captured the previtamin D-3 from a 26:74 mixture of pre- and provitamin D-3 produced by photoisomerization of provitamin D-3. (C) 2004 Elsevier Ltd. All rights reserved.

Various trialkylsilyl linked polymer supports have been prepared by reacting benzyl chloride resin and a di-Grignard reagent with CuBr.Me2S, followed by dialkylchlorosilanes. 4-Alkoxybenzyl type resin, Wang-Cl 2c and Argogel Wang-Cl 2d provided 4c and 4d at ambient temperature, whereas nonactivated resin, Merrifield 2a and Argogel-Cl 2b afforded 4a and 4b at 60degreesC. Primary and secondary alcohols 6-10 were attached to the alkyldiisopropyl-linked Wang type resin 4cA by a novel dehydrosilation with B(C6F5)(3) as well as by conventional methods. (C) 2004 Elsevier Ltd. All rights reserved.

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.

Catch and release method utilizing polymer-support was investigated in the separation of 1alpha,25-(OH)(2) pre- and provitamin D-3. Polymer-supported alkyldiisopropylsityl triflate selectively captured the previtamin D-3 from a 26:74 mixture of pre- and provitamin D-3 produced by photoisomerization of provitamin D-3. (C) 2004 Elsevier Ltd. All rights reserved.

Various trialkylsilyl linked polymer supports have been prepared by reacting benzyl chloride resin and a di-Grignard reagent with CuBr.Me2S, followed by dialkylchlorosilanes. 4-Alkoxybenzyl type resin, Wang-Cl 2c and Argogel Wang-Cl 2d provided 4c and 4d at ambient temperature, whereas nonactivated resin, Merrifield 2a and Argogel-Cl 2b afforded 4a and 4b at 60degreesC. Primary and secondary alcohols 6-10 were attached to the alkyldiisopropyl-linked Wang type resin 4cA by a novel dehydrosilation with B(C6F5)(3) as well as by conventional methods. (C) 2004 Elsevier Ltd. All rights reserved.

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.

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.