高橋 孝志

We achieved the total synthesis of macrosphelide A. as part of a combinatorial library of its analogues. The key intermediate. the seco-acid derivative, was prepared from the corresponding vinyl iodide using sequential carbonylative esterification. (C) 2003 Elsevier Ltd. All rights reserved.

We achieved the total synthesis of macrosphelide A. as part of a combinatorial library of its analogues. The key intermediate. the seco-acid derivative, was prepared from the corresponding vinyl iodide using sequential carbonylative esterification. (C) 2003 Elsevier Ltd. All rights reserved.

[GRAPHICS] We describe an efficient solid-phase synthesis of symmetric norbinaltorphimine (norBNI) derivatives 2. Pyrrole formation involving the homocoupling of two solid-supported ketones 6, followed by chemoselective and sequential N-alkylation, provided N-substituted norBNI derivatives 2. Use of this methodology led to the combinatorial synthesis of 120 norBNI derivatives.

[GRAPHICS] We describe an efficient solid-phase synthesis of symmetric norbinaltorphimine (norBNI) derivatives 2. Pyrrole formation involving the homocoupling of two solid-supported ketones 6, followed by chemoselective and sequential N-alkylation, provided N-substituted norBNI derivatives 2. Use of this methodology led to the combinatorial synthesis of 120 norBNI derivatives.

A solid-phase combinatorial synthesis approach toward the cyclic depsipeptide aurilide (1) and related analogues is described. The peptide moiety 2 was assembled on trityl linker-functionalized SynPhase Crowns using an Fmoc strategy. Optimization of the tetrapeptide assembly 5 was carried out using parallel multiple synthesis and LC/MS analysis. The aliphatic moiety 3a was coupled with the solid-supported 2 using DIC/ HOBt. Following deprotection and cleavage of linear precursor 26, macrocyclization was achieved under high dilution conditions. Removal of the methylthiomethyl protecting group provided aurilide (1) in 11% overall yield. Synthesis of a combinatorial library of aurilide derivatives 4 was accomplished with a similar protocol using the TranSort technique.

A solid-phase combinatorial synthesis approach toward the cyclic depsipeptide aurilide (1) and related analogues is described. The peptide moiety 2 was assembled on trityl linker-functionalized SynPhase Crowns using an Fmoc strategy. Optimization of the tetrapeptide assembly 5 was carried out using parallel multiple synthesis and LC/MS analysis. The aliphatic moiety 3a was coupled with the solid-supported 2 using DIC/ HOBt. Following deprotection and cleavage of linear precursor 26, macrocyclization was achieved under high dilution conditions. Removal of the methylthiomethyl protecting group provided aurilide (1) in 11% overall yield. Synthesis of a combinatorial library of aurilide derivatives 4 was accomplished with a similar protocol using the TranSort technique.

We describe a parallel and efficient synthesis of multi-branched oligosaccharides 3a-g based upon the structure of the phytoalexin elicitor active branched pentasaccharide 2. One-pot sequential orthogonal deprotection of tetrasaccharide 5 with three different protecting groups provided each of seven glycosyl acceptors 4a-g. Glycosylation of the acceptors 4a-g, followed by deprotection provided branched oligosaccharides 3a-g. All the reaction processes from scaffold 5 to 3a-g except for final hydrogenolysis were achieved utilizing an automated synthesizer in a parallel fashion. © 2003 Published by Elsevier Science Ltd.

We describe a new approach for the solid-phase synthesis of indoles 1 that involves a one-pot release and cyclization reaction of a solid-supported hydrazone through a Wang-type linker. Using this solid-phase methodology, we accomplished the synthesis of 40 naltrindole derivatives.

We describe a new approach for the solid-phase synthesis of indoles 1 that involves a one-pot release and cyclization reaction of a solid-supported hydrazone through a Wang-type linker. Using this solid-phase methodology, we accomplished the synthesis of 40 naltrindole derivatives.

We have developed a practical route for the synthesis of peptides containing unnatural amino acids. Mizoroki-Heck reaction of polymer-supported dehydroalanine, followed by asymmetric hydrogenation was accomplished using Pd(0) and Rh(l)-DuPHOS catalysts, respectively, leading to 36 dipeptides containing phenylalanine derivatives with high stereocontrol. (C) 2003 Elsevier Science Ltd. All rights reserved.

We have developed a practical route for the synthesis of peptides containing unnatural amino acids. Mizoroki-Heck reaction of polymer-supported dehydroalanine, followed by asymmetric hydrogenation was accomplished using Pd(0) and Rh(l)-DuPHOS catalysts, respectively, leading to 36 dipeptides containing phenylalanine derivatives with high stereocontrol. (C) 2003 Elsevier Science Ltd. All rights reserved.

Five types of troponoids including 40 molecules were prepared by means of palladium(0)-catalyzed carbonylation and successive acylation or benzoylation after immobilization of 2-methoxy-5-trifluoromethylsulfonyloxytropone on solid support. Four types of them showed mesophases. The final products have enough purity to detect their mesomorphic properties. (C) 2003 Elsevier Science Ltd. All rights reserved.

Five types of troponoids including 40 molecules were prepared by means of palladium(0)-catalyzed carbonylation and successive acylation or benzoylation after immobilization of 2-methoxy-5-trifluoromethylsulfonyloxytropone on solid support. Four types of them showed mesophases. The final products have enough purity to detect their mesomorphic properties. (C) 2003 Elsevier Science Ltd. All rights reserved.

A solid-phase synthesis of 2-(1-pyrazolyl)pyrimidine derivatives is described. The developed methodology allows the construction of a library of 2(1-pyrazolyl)pyrimidine.

We describe an efficient synthesis of di-branched heptasaccharide 1 having phytoalexin elicitor activity in soybeans by one-pot glycosylation. The synthesis involves chemo- and regioselective sequential six-step glycosylations using seven independent building blocks and sequential removal of acyl- and benzyl ether-type protecting groups. The coupling of seven building blocks requires only four chemoselective activitable leaving groups of glycosyl donors. Both the glycosylation and deprotection reactions can be achieved utilizing a parallel manual synthesizer.

A solid-phase synthesis of 2-(1-pyrazolyl)pyrimidine derivatives is described. The developed methodology allows the construction of a library of 2(1-pyrazolyl)pyrimidine.

We describe an efficient synthesis of di-branched heptasaccharide 1 having phytoalexin elicitor activity in soybeans by one-pot glycosylation. The synthesis involves chemo- and regioselective sequential six-step glycosylations using seven independent building blocks and sequential removal of acyl- and benzyl ether-type protecting groups. The coupling of seven building blocks requires only four chemoselective activitable leaving groups of glycosyl donors. Both the glycosylation and deprotection reactions can be achieved utilizing a parallel manual synthesizer.

A solid-phase synthesis of 2-(1-pyrazolyl)pyrimidine derivatives is described. The developed methodology allows the construction of a library of 2(1-pyrazolyl)pyrimidine.

We describe a novel reaction sequence for the solid-phase synthesis of beta-mono-substituted ketones. The methodology involves an aldol condensation reaction, followed by reduction of the resultant double bond and allows the introduction of a range of alkyl chains to solid-linked ketones at a position. Using the methodology we accomplished the synthesis of phlorizin library of 132 compounds using 43 aldehydes and four glycosyl bromides.

We describe a novel reaction sequence for the solid-phase synthesis of beta-mono-substituted ketones. The methodology involves an aldol condensation reaction, followed by reduction of the resultant double bond and allows the introduction of a range of alkyl chains to solid-linked ketones at a position. Using the methodology we accomplished the synthesis of phlorizin library of 132 compounds using 43 aldehydes and four glycosyl bromides.

A solid-phase synthesis of pentasaccharide 1 that has phytoalexin elicitor activity for rice is described. Efficient block-type synthesis by P-selective glycosylation with thioglycosides A(3) and B-2 at the 3-position of the polymer-supported glycosyl acceptor has been demonstrated.

A conformationally constrained 10-membered cyclic diamide was designed and synthesized. Conformational analysis suggested that the 9-membered ring formation was preferred to the direct formation of 10-membered ring. On the basis of the prediction, lactonization of 9-membered lactone, followed by intramolecular ester-amide transformation afforded the desired 10-membered cyclic diamide. (C) 2002 Elsevier Science Ltd. All rights reserved.

A conformationally constrained 10-membered cyclic diamide was designed and synthesized. Conformational analysis suggested that the 9-membered ring formation was preferred to the direct formation of 10-membered ring. On the basis of the prediction, lactonization of 9-membered lactone, followed by intramolecular ester-amide transformation afforded the desired 10-membered cyclic diamide. (C) 2002 Elsevier Science Ltd. All rights reserved.

The formation of the B ring of the ABC ring system of paclitaxel was accomplished by intramolecular alkylation of the protected cyanohydrin ether in the presence of the 7-alkoxy group on the C ring. A significant effect of the protective groups at the 1,2-positions was observed in this alkylation. Acyclic protection provided the desired compound 3c and 3d in moderate yields, whereas cyclic protection led to 3a in low yield.