高橋 孝志

The DNA cleaving properties of various enediyne analogues possessing sugar moieties and DNA-intercalators were investigated. The DNA cleaving experiments show that these hybrids analogues induced sequence-selective DNA cleavage and the simple sugars in the enediyne serve as a DNA recognition element for DNA cleavage. (C) 1998 Elsevier Science Ltd. All rights reserved.

Syntheses of hybrid DNA cleaving molecules which have the 9-membered enediyne structure of kedarcidin with the DNA intercalator of NCS and/or the sugar moieties were accomplished. Introduction of the sugar moieties to the masked enediyne was achieved via S-alkylation of a bromoacetate derivative with a sugar-containing thiol without the need for protection of the sugar moiety. (C) 1998 Elsevier Science Ltd. All rights reserved.

The DNA cleaving properties of various enediyne analogues possessing sugar moieties and DNA-intercalators were investigated. The DNA cleaving experiments show that these hybrids analogues induced sequence-selective DNA cleavage and the simple sugars in the enediyne serve as a DNA recognition element for DNA cleavage. (C) 1998 Elsevier Science Ltd. All rights reserved.

Syntheses of hybrid DNA cleaving molecules which have the 9-membered enediyne structure of kedarcidin with the DNA intercalator of NCS and/or the sugar moieties were accomplished. Introduction of the sugar moieties to the masked enediyne was achieved via S-alkylation of a bromoacetate derivative with a sugar-containing thiol without the need for protection of the sugar moiety. (C) 1998 Elsevier Science Ltd. All rights reserved.

This account describes our design, syntheses and DNA cleaving activities of a series of 9-membered masked enediyne analogues 8, 9, 19, 30, 44, 46, 47, 48, 49, and 50. In the first part of this report, we describe the development of a new method for the construction of 9-membered enediyne structures of NCS 8 and kedarcidin-C1027 9. The method involves the transannular [2,3]-Wittig rearrangement of the 12-membered cyclic ether to construct the highly strained 9-membered diyne. In the second part of this report, we describe the syntheses of the masked enediyne analogues of NCS 19 and kedarcidin-C1027 30 possessing trans-hydroxy groups at C(10) and C(11). Palladium-catalyzed ring-opening of the ene-oxides 27 and 34 was applied to the introduction of the trans relative stereochemistry at C(IO) and C(11) for the attachment of DNA recognition elements. Phthalic acid serves as a suitable "trigger" to control the stability of the 9-membered diynes and to generate enediynes for the DNA cleaving experiment. Both 19 and 30 caused DNA cleavage with the formation of Form II and Form III. In the last part of this report, we describe the synthesis of the masked enediyne analogues 44, 46, 47 48, 49, and 50 possessing the DNA intercalator of NCS and/or sugar moieties. DNA cleaving experiments of 44 showed that introduction of the DNA intercalators improved DNA cleaving activity about 10 fold compared with the corresponding alcohol 30. Introduction of sugar moieties to the masked enediyne was achieved via S-alkylation of a bromoacetate derivative with a sugar-containing thiol without the need for protection of the sugar moiety. DNA cleaving experiments showed that the masked enediyne analogues 46, 47, 48, 49, and 50 possessing sugar moieties induced sequence-selective DNA cleavage and that the simple sugars serve as a DNA recognition element for DNA cleavage.

The displacement of polymer-supported glucose 7 at the 6-position by azide, iodide, and acetate was achieved through a 4-hydroxybenzenesulfonate-linked Multipin(TM) system giving the corresponding glucose derivatives 8 in excellent yields. Macrocyclization of polymer-supported cyanohydrin ether 13 by displacement of the traceless sulfonate linker provided the cyclic compound 14 in moderate yield but in pure form.

This account describes our design, syntheses and DNA cleaving activities of a series of 9-membered masked enediyne analogues 8, 9, 19, 30, 44, 46, 47, 48, 49, and 50. In the first part of this report, we describe the development of a new method for the construction of 9-membered enediyne structures of NCS 8 and kedarcidin-C1027 9. The method involves the transannular [2,3]-Wittig rearrangement of the 12-membered cyclic ether to construct the highly strained 9-membered diyne. In the second part of this report, we describe the syntheses of the masked enediyne analogues of NCS 19 and kedarcidin-C1027 30 possessing trans-hydroxy groups at C(10) and C(11). Palladium-catalyzed ring-opening of the ene-oxides 27 and 34 was applied to the introduction of the trans relative stereochemistry at C(IO) and C(11) for the attachment of DNA recognition elements. Phthalic acid serves as a suitable "trigger" to control the stability of the 9-membered diynes and to generate enediynes for the DNA cleaving experiment. Both 19 and 30 caused DNA cleavage with the formation of Form II and Form III. In the last part of this report, we describe the synthesis of the masked enediyne analogues 44, 46, 47 48, 49, and 50 possessing the DNA intercalator of NCS and/or sugar moieties. DNA cleaving experiments of 44 showed that introduction of the DNA intercalators improved DNA cleaving activity about 10 fold compared with the corresponding alcohol 30. Introduction of sugar moieties to the masked enediyne was achieved via S-alkylation of a bromoacetate derivative with a sugar-containing thiol without the need for protection of the sugar moiety. DNA cleaving experiments showed that the masked enediyne analogues 46, 47, 48, 49, and 50 possessing sugar moieties induced sequence-selective DNA cleavage and that the simple sugars serve as a DNA recognition element for DNA cleavage.

This account describes our design, syntheses and DNA cleaving activities of a series of 9-membered masked enediyne analogues 8, 9, 19, 30, 44, 46, 47, 48, 49, and 50. In the first part of this report, we describe the development of a new method for the construction of 9-membered enediyne structures of NCS 8 and kedarcidin-C1027 9. The method involves the transannular [2,3]-Wittig rearrangement of the 12-membered cyclic ether to construct the highly strained 9-membered diyne. In the second part of this report, we describe the syntheses of the masked enediyne analogues of NCS 19 and kedarcidin-C1027 30 possessing trans-hydroxy groups at C(10) and C(11). Palladium-catalyzed ring-opening of the ene-oxides 27 and 34 was applied to the introduction of the trans relative stereochemistry at C(IO) and C(11) for the attachment of DNA recognition elements. Phthalic acid serves as a suitable "trigger" to control the stability of the 9-membered diynes and to generate enediynes for the DNA cleaving experiment. Both 19 and 30 caused DNA cleavage with the formation of Form II and Form III. In the last part of this report, we describe the synthesis of the masked enediyne analogues 44, 46, 47 48, 49, and 50 possessing the DNA intercalator of NCS and/or sugar moieties. DNA cleaving experiments of 44 showed that introduction of the DNA intercalators improved DNA cleaving activity about 10 fold compared with the corresponding alcohol 30. Introduction of sugar moieties to the masked enediyne was achieved via S-alkylation of a bromoacetate derivative with a sugar-containing thiol without the need for protection of the sugar moiety. DNA cleaving experiments showed that the masked enediyne analogues 46, 47, 48, 49, and 50 possessing sugar moieties induced sequence-selective DNA cleavage and that the simple sugars serve as a DNA recognition element for DNA cleavage.

The displacement of polymer-supported glucose 7 at the 6-position by azide, iodide, and acetate was achieved through a 4-hydroxybenzenesulfonate-linked Multipin(TM) system giving the corresponding glucose derivatives 8 in excellent yields. Macrocyclization of polymer-supported cyanohydrin ether 13 by displacement of the traceless sulfonate linker provided the cyclic compound 14 in moderate yield but in pure form.

Rh(I)-catalyzed hydroformylation of a polymer-supported 1,1-disubstituted alkene was carried out on the Multipin(TM) system. The reaction proceeded under 75 atm of syngas (H-2 : CO = 1 : 1) providing the corresponding aldehyde on the solid support. Optimization of the reaction conditions is described. (C) 1998 Elsevier Science Ltd. All rights reserved.

Rh(I)-catalyzed hydroformylation of a polymer-supported 1,1-disubstituted alkene was carried out on the Multipin(TM) system. The reaction proceeded under 75 atm of syngas (H-2 : CO = 1 : 1) providing the corresponding aldehyde on the solid support. Optimization of the reaction conditions is described. (C) 1998 Elsevier Science Ltd. All rights reserved.

Glycosidation, using the methylthio derivative of N-acetylneuraminic acid 3, of linker alcohol 4 in DME with "long-range participation" produced the alpha-glycosyl linkage with high stereoselectivity. The alpha-linked sialic acid 2 was introduced in taxol without protection of the alcohol functionality in sialic acid. (C) 1997 Elsevier Science Ltd. All rights reserved.

Syntheses of the proposed structure of periplanone J (3) and its diastereomer (4), and the discussion on the true structure of PJ based on spectral analysis of 3,4 and the natural PJ are described.

Glycosidation, using the methylthio derivative of N-acetylneuraminic acid 3, of linker alcohol 4 in DME with "long-range participation" produced the alpha-glycosyl linkage with high stereoselectivity. The alpha-linked sialic acid 2 was introduced in taxol without protection of the alcohol functionality in sialic acid. (C) 1997 Elsevier Science Ltd. All rights reserved.

Syntheses of the proposed structure of periplanone J (3) and its diastereomer (4), and the discussion on the true structure of PJ based on spectral analysis of 3,4 and the natural PJ are described.

This account describes our design, syntheses and DNA cleaving activities of a series of 9-membered masked enediyne analogues 8, 9, 19, 30, 44, 46, 47, 48, 49, and 50, In the first part of this report, we describe the development of a new method for the construction of 9-membered enediyne structures of NCS 8 and kedarcidin-C1027 9. The method involves the transannular [2,3]-Wittig rearrangement of the 12-membered cyclic ether to construct the highly strained 9-membered diyne. In the second part of this report, we describe the syntheses of the masked enediyne analogues of NCS 19 and kedarcidin-C1027 30 possessing trans-hydroxy groups at C(10) and C(11). Palladium-catalyzed ring-opening of the ene-oxides 27 and 34 was applied to the introduction of the irons relative stereochemistry at C(10) and C(11) for the attachment of DNA recognition elements. Phthalic acid serves as a suitable "trigger" to control the stability of the 9-membered diynes and to generate enediynes for the DNA cleaving experiment. Both 19 and 30 caused DNA cleavage with the formation of Form II and Form III. In the last part of this report, we describe the synthesis of the masked enediyne analogues 44, 46, 47, 48, 49, and 50 possessing the DNA intercalator of NCS and/or sugar moieties. DNA cleaving experiments of 44 showed that introduction of the DNA interpolators improved DNA cleaving activity about 10 fold compared with the corresponding alcohol 30. Introduction of sugar moieties to the masked enediyne was achieved via S-alkylation of a bromoacetate derivative with a sugar-containing thiol without the need for protection of the sugar moiety. DNA cleaving experiments showed that the masked enediyne analogues 46, 47, 48, 49, and 50 possessing sugar moieties induced sequence-selective DNA cleavage and that the simple sugars serve as a DNA recognition element for DNA cleavage.

Syntheses of KDO and KDN by alkylation of 2-alkoxy-2-cyanoacetate anion, an acyl anion equivalent of alkyl glyoxylate, with a sugar-derived iodide and triflate are described.

N-Acetylneuraminic acid was synthesized via alkylation of 2-alkoxy-2-cyanoacetate anion, an acyl anion equivalent of alkyl glyoxylate, with a sugar-derived bromide prepared from D-glycero-D-gulo-heptose-1,4-lactone.

N-Acetylneuraminic acid was synthesized via alkylation of 2-alkoxy-2-cyanoacetate anion, an acyl anion equivalent of alkyl glyoxylate, with a sugar-derived bromide prepared from D-glycero-D-gulo-heptose-1,4-lactone.

Syntheses of KDO and KDN by alkylation of 2-alkoxy-2-cyanoacetate anion, an acyl anion equivalent of alkyl glyoxylate, with a sugar-derived iodide and triflate are described. (C) 1997 Elsevier Science Ltd.

Syntheses of the A-ring and the chiral C-ring model of taxol by using the intramolecular nitrile oxide cycloaddition and its diastereoselectivity based on MM2 transition state model are described.

Syntheses of the A-ring and the chiral C-ring model of taxol by using the intramolecular nitrile oxide cycloaddition and its diastereoselectivity based on MM2 transition state model are described. (C) 1997 Elsevier Science Ltd.

A short and efficient synthesis of 1 alpha, 25-dihydroxyvitamin D-3 A-ring synthon starting from diketene, acrolein and ethyl malonate by using palladium-catalyzed cyclization of the Q-enol triflate is described.

A short and efficient synthesis of 1 alpha, 25-dihydroxyvitamin D-3 A-ring synthon starting from diketene, acrolein and ethyl malonate by using palladium-catalyzed cyclization of the Q-enol triflate is described.

We describe a remote glycosidation that allows us to form a branched trisaccharide in intramolecular fashion. The molecular design of the spacer molecule for the remote glycosidation was examined based on molecular mechanics calculations. Copyright (C) 1996 Elsevier Science Ltd

The seco-B-ring triene system of 1 alpha,2 beta,25-trihydroxy-vitamin D3 is efficiently constructed by means of a palladium-catalyzed cyclization of the dienol triflate. (C) 1997, Elsevier Science Ltd. All rights reserved.

The stereoselective synthesis of a taxol intermediate via a biomimetic route is described. Aldol condensation of gamma-butyrolactone and citral derivatives generated three stereogenic centers at positions C1, C2, and C11 corresponding to taxol. Intramolecular alkylation of the cyanohydrin ether efficiently formed the 12-membered ring system in which stereoselective reduction, followed by directed epoxidation, afforded the key intermediate epoxide.