Faculty Profiles - ABE Hiroshi

Destabilizing universal linkers for signal amplification in self-ligating probes for RNA. Reviewed

Abe H, Kool ET

Journal of the American Chemical Society Vol. 126 ( 43 ) page： 13980-6 2004.11

An efficient synthesis of beta-C-glycosides based on the conformational restriction strategy: Lewis acid promoted silane reduction of the anomeric position with complete stereoselectivity Reviewed

M Terauchi, H Abe, A Matsuda, S Shuto

ORGANIC LETTERS Vol. 6 ( 21 ) page： 3751 - 3754 2004.10

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER CHEMICAL SOC

The reduction of glyconolactols having an anomeric carbon substituent by Et3SiH/TMSOTf proceeded with complete stereoselectivity to produce the corresponding beta-C-glycosides when the substrates were conformationally restricted in the C-4(1)-chair form by a 3,4-O-cyclic diketal or a 4,6-O-benzylidene protecting group. Thus, the efficient construction beta-C-glycosides was achieved on the basis of the conformation restriction strategy.

DOI： 10.1021/ol048525+

Stereoselective synthesis of alpha- and beta-C-glucosides via radical cyclization with an allylsilyl tether. Control of the stereoselectivity by changing the conformation of the pyranose ring (vol 41, pg 4151, 2000) Reviewed

S Shuto, M Terauchi, Y Yahiro, H Abe, S Ichikawa, A Matsuda

TETRAHEDRON LETTERS Vol. 45 ( 36 ) page： 6819 - 6819 2004.8

The unusual 1,4-chelation-controlled nucleophilic addition to aldehydes with high stereoselectivity. A systematic study of stereoselectivity in the addition reaction of carbon nucleophiles to cis-substituted cyclopropanecarbaldehydes Reviewed

Y Kazuta, H Abe, T Yamamoto, A Matsuda, S Shuto

TETRAHEDRON Vol. 60 ( 31 ) page： 6689 - 6703 2004.7

Language：English Publishing type：Research paper (scientific journal) Publisher：PERGAMON-ELSEVIER SCIENCE LTD

The addition reaction of carbon nucleophiles to cis-substituted cyclopropanecarbaldehydes was systematically investigated. Ab initio calculations of model cyclopropanecarbaldehydes suggested that the bisected s-cis and s-trans conformers are the only two minimum energy conformers, which are stabilized due to the pi-donating stereoelectronic effect of the cyclopropane ring. The experimental results of a series of substrates, that is, cyclopropanecarbaldehydes 1-5 bearing a cis-(tert-butyldiphenyisilyloxy)methyl group, a cis-benzyloxymethyl group, a cis-(p-methoxybenzyloxy)methyl group, cis-N,N-diethylcarbamoyl and trans-phenyl groups, and cis-(tert-butyldiphenylsilyloxy)methyl and trans-phenyl groups, respectively, showed that highly anti-selective Grignard additions could be realized. It turned out that it occurred via an unusual 7-membered 1,4-chelation-controlled pathway. Highly stereoselective Grignard addition via the chelation-controlled pathway occurred even in the reaction of the usually non-chelating silyl ether-type substrate 5. The results have great importance because the 1,4-chelation-controlled stereoselective addition reactions can indeed be realized. Under non-chelation conditions, the syn-products were produced with moderate stereoselectivity, which are likely to be formed via the bisected s-cis conformation-like transition state stabilized by the characteristic orbital interaction. These reactions, especially the chelation-controlled reaction, should be useful because of their t stereoselectivity and stereochemical predictability. (C) 2004 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tet.2004.05.063

Quenched auto-ligating DNAs: Multicolor identification of nucleic acids at single nucleotide resolution Reviewed

S Sando, H Abe, ET Kool

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Vol. 126 ( 4 ) page： 1081 - 1087 2004.2

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER CHEMICAL SOC

We describe the synthesis and study of multicolor quenched autoligating (QUAL) probes for identification and discrimination of closely related RNA and DNA sequences in solution and in bacteria. In these probes, a dabsyl quencher doubles as an activator in the oligonucleotide-joining reaction. The oligonucleotides remain dark until they bind at adjacent sites, and "light up" on nucleophilic displacement of the dabsyl probe by the phosphorothioate probe. Four fluorescent dye conjugates were prepared and tested with probes and targets that differ by one nucleotide. Experiments on polymer beads show clear color-based discrimination of DNAs added in solution. Two-color quenched probe pairs were then tested in the discrimination of 16S rRNA sequences in Escherichia coli. Single nucleotide resolution was achieved in the cells with green/red QUAL probes, allowing identification of a one-base sequencing error in the 16S rRNA database. Finally, QUAL probes were successfully applied in live bacterial cells. The method requires only incubation followed by fluorescence imaging, and requires no enzymes, added reagents, cross-linking, fixing, or washes. Because probes must bind side-by-side to generate signal, there is little or no interference from unintended protein binding, which can occur with other probe types. The results suggest that QUAL probes may be of general use in the detection and identification of sequences in solution, on microarrays, and in microorganisms.

DOI： 10.1021/ja038665z

Construction of a cis-cyclopropane via reductive radical decarboxylation. Enantioselective synthesis of cis- and trans-1-arylpiperazyl-2-phenyleyclopropanes designed as antidopaminergic agents Reviewed

K Yamaguchi, Y Kazuta, H Abe, A Matsuda, S Shuto

JOURNAL OF ORGANIC CHEMISTRY Vol. 68 ( 24 ) page： 9255 - 9262 2003.11

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER CHEMICAL SOC

(1S,2S)-, (1S,2R)-, and (1R,2S)-1-(2,4-Dimethylphenyl)piperazyl-2-phenylcyclopropane (2a, 3, and ent-3, respectively), which were designed as conformationally restricted analogues of haloperidol (1), a clinically effective antipsychotic agent, were synthesized from chiral epichlorohydrins using the Barton reductive radical decarboxylation as the key step. (1S,2R)-1-(tert-Butyldiphenylsilyloxy)methyl-2-carboxy-2-phenylcyclopropane (5), which was prepared from (S)-epichlorohydrin ((S)-7), was converted into its N-hydroxypyridine-2-thione ester 12, the substrate for the reductive radical decarboxylation. When 12 was treated with TMS(3)SiH in the presence of Et(3)B or AIBN, the decarboxylation and subsequent hydride attack on the cyclopropyl radical intermediate from the side opposite to the bulky silyloxymethyl moiety occurred, resulting in selective formation of the corresponding reductive decarboxylation product 4-cis with the cis-cyclopropane structure. From 4-cis, the cis-cyclopropane-type target compound 3 was readily synthesized. Starting from (R)epichlorohydrin ((R)-7), ent-3 was similarly synthesized. Epimerization of the cyclopropanecarboxamide ent-16-cis, a synthetic intermediate for ent-3, on treatment with a base prepared from Bu(2)Mg and i-Pr(2)NH in THF occurred effectively to give the corresponding trans isomer 16-trans, which was converted into 2a with the trans-cyclopropane structure.

DOI： 10.1021/jo0302206

A study on the conformation-anomeric effect-stereoselectivity relationship in anomeric radical reactions, using conformationally restricted glucose derivatives as substrates Reviewed

H Abe, M Terauchi, A Matsuda, S Shuto

JOURNAL OF ORGANIC CHEMISTRY Vol. 68 ( 19 ) page： 7439 - 7447 2003.9

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER CHEMICAL SOC

We previously theorized that, since the stereoselectivity of anomeric radical reactions is significantly influenced by the kinetic anomeric effect, which can be controlled by restricting the conformation of the radical intermediate, the proper conformational restriction of the pyranose ring of the substrates would therefore make highly alpha- and beta-stereoselective anomeric radical reactions possible. This theory was based on our previous results of the anomeric radical reactions with D-xylose derivatives as the substrates. We herein report the anomeric radical deuteration reactions with the conformationally restricted 1-phenylseleno-D-glucose derivatives, 2g and 3g, restricted in a C-4(1)-conformation by an beta-cyclic diketal moiety, and 4g, 5g, 6g, 7g, and 8g, restricted in a C-1(4)-conformation by bulky O-silyl protecting groups. The radical deuterations with Bu3SnD, using the C-4(1)-restricted substrates 2g and 3g, afforded the corresponding alpha-products (alpha/beta = 98:2) highly stereoselectively, whereas the C-1(4)-restricted substrate 6g, having a trigonal (sp(2)) carbon substituent, i.e., -CHO, at the 5-position, selectively gave the beta-products (alpha/beta = 0: 100). Thus, the stereoselectivity was significantly increased by the conformational restriction and was completely inverted by changing the substrate conformation from the C-4(1)-form to the C-1(4)-form. On the other hand, the deuterations with the C-1(4)-restricted substrates 4g and 5g showed that the 1,5-steric effect due to the tetrahedral carbon substituent (-CH2OTIPS or -CH2OH) at the 5-axial position dominantly prevented the hydride transfer from the beta-face competing with the kinetic anomeric effect. This study suggests that, depending on the restricted conformation of the substrates to the C-4(1)- or the C-1(4)-form, the alpha- or beta-products would be obtained highly stereoselectively via anomeric radical reactions of hexopyranoses.

DOI： 10.1021/jo030128+

A systematic study of the hydride reduction of cyclopropyl ketones with structurally simplified substrates. Highly stereoselective reductions of trans-substituted cyclopropyl ketones via the bisected s-cis conformation Reviewed

Y Kazuta, H Abe, T Yamamoto, A Matsuda, S Shuto

JOURNAL OF ORGANIC CHEMISTRY Vol. 68 ( 9 ) page： 3511 - 3521 2003.5

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER CHEMICAL SOC

The stereoselective hydride reduction of the cis- and trans-substituted cyclopropyl ketones was systematically investigated using a series of structurally simplified substrates, trans-[tert-butyldiphenylsilyloxymethyl]cyclopropyl ketones la-a and trans- (benzyloxymethyl)cyclopropyl methyl ketone (2), and the corresponding cis congeners 3a,b,e and 4. The results showed that, not only in the reduction of the cis-substituted cyclopropyl ketones but also in that of the trans-substituted ketones, high stereoselectivity can be realized when the substrate has a bulky substituent on the cyclopropane ring, even though it is attached to the position trans to the acyl moiety. Ab initio calculations based on the density functional theory (DFT) of cyclopropyl ketones showed that (1) the bisected s-cis and s-trans conformers were the only two minimum energy conformers; while the s-cis conformer was more stable than the s-trans and (2) a bulky alkyl group in the acyl moiety and a cis substituent on the cyclopropane ring made the bisected s-cis conformer much more stable. On the basis of these calculations and experimental results, it is likely that the more stable the bisected s-cis conformer of the substrate, the more stereoselective the hydride reduction. Thus, the stereochemistry can be explained by hydride attack on the bisected s-cis conformation of the substrate from the less-hindered face. The predictability of the stereochemical results is predicated on the bisected s-cis transition-state model, which is very important from the viewpoint of synthetic organic chemistry.

DOI： 10.1021/jo030019v

Control of alpha/beta stereoselectivity in Lewis acid promoted C-glycosidations using a controlling anomeric effect based on the conformational restriction strategy Reviewed

S Tamura, H Abe, A Matsuda, S Shuto

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Vol. 42 ( 9 ) page： 1021 - + 2003

Development of New Radical Reactions with a Vinylsilyl Group and Their Application to the Synthesis of Branched-Chain Sugar Nucleosides

Satoshi Shuto, Makiko Kanazaki, Isamu Sugimoto, Satoshi Ichikawa, Yuki Nagasawa, Yoshihito Ueno, Hiroshi Abe, Noriaki Minakawa, Makoto Sukeda, Tetsuya Kodama, Makoto Nomura, Akira Matsuda

Recent Advances in Nucleosides: Chemistry and Chemotherapy page： 21 - 55 2002

Synthesis and biological activity of adenophostin derivatives as IP3 receptor ligands. Reviewed

Shuto S, Mochizuki T, Abe H, Kondo Y, Matsuda A

Nucleic acids research. Supplement (2001) ( 2 ) page： 23-4 2002

Development of new radical reactions with a vinylsilyl group and their application to the synthesis of branched-chain sugar nucleosides

Satoshi Shuto, Maki kanazaki, Isamu Sugimoto, Satoshi Ichikawa, Yuki Nagasawa, Yoshihito Ueno, Hiroshi Abe, Noriaki Minakawa, Makoto Sukeda, Tetsuya Kodama, Makoto Nomura, Akira matsuda

Recent Advances in Nucleosides page： 21-55 2002

Synthesis and biological activity of adenophostin derivatives as IP3 receptor ligands Reviewed

Satoshi Shuto, Tetsuya Mochizuki, Hiroshi Abe, Yoshihiko Kondo, Akira Matsuda

Nucleic Acids Symposium Series Vol. 2 page： 23 - 24 2002

Highly alpha- and beta-selective radical C-glycosylation reactions using a controlling anomeric effect based on the conformational restriction strategy. A study on the conformation-anomeric effect-stereoselectivity relationship in anomeric radical reactions Reviewed

H Abe, S Shuto, A Matsuda

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Vol. 123 ( 48 ) page： 11870 - 11882 2001.12

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER CHEMICAL SOC

We hypothesized that, because the stereoselectivity of anomeric radical reactions was significantly influenced by the anomeric effect, which can be controlled by restricting the conformation of the radical intermediate, the proper conformational restriction of the pyranose ring of the substrates would therefore make highly alpha- and beta -stereoselective anomeric radical reactions possible. Thus, the conformationally restricted 1-phenylseleno-D-xylose derivatives 9 and 10, restricted in a C-4(1)-conformation, and 11 and 12, restricted in a C-1(4)-conformation, were designed and synthesized by introducing the proper protecting groups on the hydroxyl groups on the pyranose ring as model substrates for the anomeric radical reactions. The radical deuterations with Bu3SnD and the C-glycosylation with Bu3SnCH2CH=CH2 or CH2 CHCN, using the C-4(1)-restricted substrates 9 and 10, afforded the corresponding alpha -products (alpha/beta = 97:3-85:15) highly stereoselectively, whereas the C-1(4)-restricted substrates 11 and 12 selectively gave the fl-products (alpha/beta = 1:99-0:100). Thus, stereoselectivity was significantly increased by conformational restriction and was completely inverted by changing the substrate conformation from the C-4(1)-form into the C-1(4)-form. Ab initio, calculations suggested that the radical intermediates produced from these substrates possessed the typical C-4(1)- or C-1(4)-Conformation, which was similar to that of the substrates, and that the anomeric effect in these conformations would be the factor controlling the transition state of the reaction. Therefore, the highly alpha- and beta -selective reactions would occur because of the anomeric effect, which could be manipulated by conformational restriction of the substrates, as expected. This would be the first radical C-glycosylation reaction to provide both alpha- and beta -C-glycosides highly stereoselectively.

DOI： 10.1021/ja011321t

An efficient method for preparing fully O-silylated pyranoses conformationally restricted in the unusual C-1(4)-form Reviewed

H Abe, S Shuto, S Tamura, A Matsuda

TETRAHEDRON LETTERS Vol. 42 ( 35 ) page： 6159 - 6161 2001.8

Language：English Publishing type：Research paper (scientific journal) Publisher：PERGAMON-ELSEVIER SCIENCE LTD

An efficient method for preparing fully O-silylated pyranoses, which are conformationally restricted in the unusual C-1(4)-form, was developed. Thus, successive treatment of pyranosides, such as xylose and glucose derivatives, with NaH and TIPSOTf or TBSOTf in THF at room temperature gave the corresponding fully O-silylated products. (C) 2001 Elsevier Science Ltd. All rights reserved.

DOI： 10.1016/S0040-4039(01)01233-3

Significance of substrate hydrophobicity for recognition by an oligopeptide transporter (PEPT1) Reviewed

R Tateoka, H Abe, S Miyauchi, S Shuto, A Matsuda, M Kobayashi, K Miyazaki, N Kamo

BIOCONJUGATE CHEMISTRY Vol. 12 ( 4 ) page： 485 - 492 2001.7

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER CHEMICAL SOC

Our previous paper [(1999) Bioconjugate Chem. 10, 24-31] pointed out that hydrophobicity of substrates/inhibitors plays an important role in the recognition by an oligopeptide transporter (PEPT1) expressed in the human intestinal epithelial cell line Caco-8. To determine the significance of that hydrophobicity, we have now synthesized dipeptide analogues conjugating the E-amino group of Lys in Val-Lys with aliphatic carboxylic acids: acetic acid (C2), propanoic acid (C3), pentanoic acid (C5), hexanoic acid (C6), and decanoic acid (C10). The affinities of these conjugates were estimated by their inhibition of the accumulation rate of Gly-Sar, a well-established substrate for PEPT1. With the increase in length of the hydrocarbon chain of the conjugates, i.e., in the hydrophobicity of the conjugates, the inhibition strengthened. Dixon-Webb plot analysis of the inhibition by the C10-conjugated dipeptide showed competitive inhibition. The trans-stimulation effect of Val-Lys conjugated to C10 or C5 on the uptake of Ceftibuten was observed using rat brush border membrane vesicles. This findings showed that these conjugates are transportable substrates. These results confirmed that the hydrophobicity of substrates/inhibitor is one of the factors in the recognition by PEPT1.

DOI： 10.1021/bc000135u