高橋 孝志

A solid-phase synthesis of 6-sulfonylamino morphinan has been developed. The morphinan derivatives were designed as selective opioid ligands. The sulfonamide moiety was introduced by reductive amination of a ketone on solid phase, followed by sulfonylation of the resulting amine. Using this methodology, the synthesis of three combinatorial libraries was accomplished to prepare 339 morphinan derivatives with over 70% purity.

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.

A solid-phase synthesis of 6-sulfonylamino morphinan has been developed. The morphinan derivatives were designed as selective opioid ligands. The sulfonamide moiety was introduced by reductive amination of a ketone on solid phase, followed by sulfonylation of the resulting amine. Using this methodology, the synthesis of three combinatorial libraries was accomplished to prepare 339 morphinan derivatives with over 70% purity.

We describe a highly convergent approach for the synthesis of the tetraglucosyl glucitol 1 and its derivatives 4, 5 and 6 which exhibit phytoalexin-elicitor activity in rice cells based on sequential glycosylation. © 2001 Elsevier Science Ltd. All rights reserved.

We describe a highly convergent approach for the synthesis of the tetraglucosyl glucitol 1 and its derivatives 4, 5 and 6 which exhibit phytoalexin-elicitor activity in rice cells based on sequential glycosylation. © 2001 Elsevier Science Ltd. All rights reserved.

We describe a highly convergent approach for the synthesis of the tetraglucosyl glucitol 1 and its derivatives 4. 5 and 6 which exhibit phytoalexin-elicitor activity in rice cells based on sequential glycosylation. (C), 2001 Elsevier Science Ltd. All rights reserved.

We have developed a practical synthetic route for the A and C rings of paclitaxel. The key reaction is a Ti-mediated radical cyclization of an epoxyalkene. (C) 2001 Elsevier Science Ltd. All rights reserved.

We have developed a practical synthetic route to the CD ring of paclitaxel. Unsaturated ester 8 was stereo- and regioselectively isomerized to 9. Stereoselective introduction of hydroxy groups and oxetane formation provided potential intermediate 4, which was coupled to an A ring moiety. (C) 2001 Elsevier Science Ltd. All rights reserved.

We have developed a practical synthetic route for the A and C rings of paclitaxel. The key reaction is a Ti-mediated radical cyclization of an epoxyalkene. (C) 2001 Elsevier Science Ltd. All rights reserved.

We have developed a practical synthetic route to the CD ring of paclitaxel. Unsaturated ester 8 was stereo- and regioselectively isomerized to 9. Stereoselective introduction of hydroxy groups and oxetane formation provided potential intermediate 4, which was coupled to an A ring moiety. (C) 2001 Elsevier Science Ltd. All rights reserved.

A solid-phase synthesis of enediyne molecules containing a sugar moiety is reported, polymer-supported (2-mercaptoethyl)glycosides linked through a trialkylsilane linker were coupled to a bromoacetate on an enediyne by S-alkylation. After simple washing of the polymer, mild acid treatment, and evaporation, the desired oligosaccharide conjugated enediynes were isolated in pure form in parallel fashion.

A solid-phase synthesis of enediyne molecules containing a sugar moiety is reported, polymer-supported (2-mercaptoethyl)glycosides linked through a trialkylsilane linker were coupled to a bromoacetate on an enediyne by S-alkylation. After simple washing of the polymer, mild acid treatment, and evaporation, the desired oligosaccharide conjugated enediynes were isolated in pure form in parallel fashion.

A highly efficient synthesis of the vitamin D-3 system on solid support is described. Two synthetic strategies for the solid-phase synthesis of vitamin D-3 were developed. One is,for 11-hydroxy analogues, and the other is for most other synthetic analogues. In the latter strategy, the sulfonate-linked CD-ring 58 was initially immobilized an PS-DES resin to give solid-supported CD-ring 63 (Scheme 10). Similarly, solid-supported CD-ring 63 was prepared by attachment of the CD-ring 10 to the chlorosulfonate resin 63. The vitamin D3 system was synthesized by Homer-Wadsworth-Emmons reaction of the A-ring phosphine oxide to a solid-supported CD-ring, followed by simultaneous introduction of the side chain and cleavage from resin with a Cu-1-catalyzed Grignard reagent. Parallel synthesis of the vitamin Dg analogues was accomplished by a split and pool methodology utilizing radio frequency encoded combinatorial chemistry, and a manual parallel synthesizer for side chain diversification and deprotection. Additionally, we demonstrated the synthesis of various A-rings in a similar protocol for efficient preparation of building blocks.

A highly efficient synthesis of the vitamin D-3 system on solid support is described. Two synthetic strategies for the solid-phase synthesis of vitamin D-3 were developed. One is,for 11-hydroxy analogues, and the other is for most other synthetic analogues. In the latter strategy, the sulfonate-linked CD-ring 58 was initially immobilized an PS-DES resin to give solid-supported CD-ring 63 (Scheme 10). Similarly, solid-supported CD-ring 63 was prepared by attachment of the CD-ring 10 to the chlorosulfonate resin 63. The vitamin D3 system was synthesized by Homer-Wadsworth-Emmons reaction of the A-ring phosphine oxide to a solid-supported CD-ring, followed by simultaneous introduction of the side chain and cleavage from resin with a Cu-1-catalyzed Grignard reagent. Parallel synthesis of the vitamin Dg analogues was accomplished by a split and pool methodology utilizing radio frequency encoded combinatorial chemistry, and a manual parallel synthesizer for side chain diversification and deprotection. Additionally, we demonstrated the synthesis of various A-rings in a similar protocol for efficient preparation of building blocks.

We have developed a practical synthetic route to constrained P-strand mimetic templates by regioselective 1,3-dipolar cycloaddition of azomethine imines with vinyl sulfone. A small library of P-strand mimetic templates was generated which include potent and selective inhibitors of serine proteases. (C) 2001 Elsevier Science Ltd. All rights reserved.

We have developed a practical synthetic route to constrained P-strand mimetic templates by regioselective 1,3-dipolar cycloaddition of azomethine imines with vinyl sulfone. A small library of P-strand mimetic templates was generated which include potent and selective inhibitors of serine proteases. (C) 2001 Elsevier Science Ltd. All rights reserved.

A library of 72 trisaccharides constructed from a combination of glucosides, galactosides, and mannosides via solution-phase one-pot glycosylation was synthesized rapidly using a manual synthesizer. (C) 2000 Elsevier Science Ltd. All rights reserved.

A library of 72 trisaccharides constructed from a combination of glucosides, galactosides, and mannosides via solution-phase one-pot glycosylation was synthesized rapidly using a manual synthesizer. (C) 2000 Elsevier Science Ltd. All rights reserved.

[GRAPHICS] We developed a new method for alpha-glycoside formation of sialyl conjugates based on alkylation and subsequent intramolecular glycosidation of 2-alkoxy-2-phenylthioacetate. By this method we succeeded in the syntheses of G(M4) and G(M3) intermediates.

Pd(0)-catalyzed carbonylation using carbon monoxide and various aryl iodides with polymer-supported primary and secondary alcohols, and primary amines was accomplished. (C) 1999 Elsevier Science Ltd. All rights reserved.

Pd(0)-catalyzed carbonylation using carbon monoxide and various aryl iodides with polymer-supported primary and secondary alcohols, and primary amines was accomplished. (C) 1999 Elsevier Science Ltd. All rights reserved.

Pd(0)-catalyzed carbonylation using carbon monoxide and various aryl iodides with polymer-supported primary and secondary alcohols, and primary amines was accomplished. (C) 1999 Elsevier Science Ltd. All rights reserved.

One-pot glycosylations of glycosyl bromides and phenylthio glycosides with various dihydroxyl glycosyl accepters have been examined to provide the corresponding branched trisaccharides. (C) 1999 Elsevier Science Ltd. All rights reserved.

One-pot glycosylations of glycosyl bromides and phenylthio glycosides with various dihydroxyl glycosyl accepters have been examined to provide the corresponding branched trisaccharides. (C) 1999 Elsevier Science Ltd. All rights reserved.

Glycosidation of silicon-connected glycosyl donors on polystyrene resin is described Thiophenyl glycoside 2a and glucopyranosyl fluoride 2 b reacted with glycosyl acceptor 3 (R-2 = Bn) to give disaccharide 4a in 96% and 70% yields, respectively. Glycosidation of thiophenyl glucoside 2a (R-1 =Bn or Bz) with glycosyl acceptor 3 (R-2 =Bn or Ac) yielded 4a-4c in satisfactory yields and 4d in moderate yield. (C) 1999 Elsevier Science Ltd. All rights reserved.

Glycosidation of silicon-connected glycosyl donors on polystyrene resin is described Thiophenyl glycoside 2a and glucopyranosyl fluoride 2 b reacted with glycosyl acceptor 3 (R-2 = Bn) to give disaccharide 4a in 96% and 70% yields, respectively. Glycosidation of thiophenyl glucoside 2a (R-1 =Bn or Bz) with glycosyl acceptor 3 (R-2 =Bn or Ac) yielded 4a-4c in satisfactory yields and 4d in moderate yield. (C) 1999 Elsevier Science Ltd. All rights reserved.