Kazunobu Toshima

Regio- and stereoselective β-mannosylation using a boronic acid catalyst and its application in the synthesis of a tetrasaccharide repeating unit of lipopolysaccharide derived from E. coli O75

Co-reporter:Nobuya Nishi;Junki Nashida;Eisuke Kaji;Daisuke Takahashi

Chemical Communications 2017 vol. 53(Issue 21) pp:3018-3021

Publication Date(Web):2017/03/09

DOI:10.1039/C7CC00269F

Regio- and stereoselective β-mannosylations using 1,2-anhydromannose and diol sugar acceptors in the presence of a boronic acid catalyst proceeded smoothly to give the corresponding β-mannosides with high regio- and β-stereoselectivities in high yields without further additives under mild conditions. In addition, this glycosylation method was applied successfully to the synthesis of a tetrasaccharide repeating unit of lipopolysaccharide (LPS) derived from E. coli O75.

1,2-cis-α-Stereoselective Glycosylation Utilizing a Glycosyl-Acceptor-Derived Borinic Ester and Its Application to the Total Synthesis of Natural Glycosphingolipids

Co-reporter:Masamichi Tanaka, Daisuke Takahashi, and Kazunobu Toshima

Organic Letters 2016 Volume 18(Issue 19) pp:5030-5033

Publication Date(Web):September 14, 2016

DOI:10.1021/acs.orglett.6b02488

1,2-cis-α-Stereoselective glycosylations were conducted using a 1,2-anhydroglucose donor and mono-ol acceptors in the presence of a glycosyl-acceptor-derived borinic ester. Reactions proceeded smoothly under mild conditions to provide the corresponding α-glycosides with high stereoselectivity in moderate to high yields. In addition, the present method was applied successfully to the direct glycosylation of a protected ceramide acceptor and the total synthesis of natural glycosphingolipids (GSLs).

Stereocontrolled Photoinduced Glycosylation Using an Aryl Thiourea as an Organo photoacid

Co-reporter:Tomoya Kimura, Takahiro Eto, Daisuke Takahashi, and Kazunobu Toshima

Organic Letters 2016 Volume 18(Issue 13) pp:3190-3193

Publication Date(Web):June 23, 2016

DOI:10.1021/acs.orglett.6b01404

Photoinduced glycosylation of alcohols with α-glucosyl trichloroacetimidates, using aryl urea and thioureas as organo photoacids, was examined under long wavelength UV (ultraviolet) irradiation. The results show, for the first time, that such glycosylations proceed effectively to give the corresponding glycosides in high yields. In addition, high β-stereoselectivity was obtained under high concentration conditions, whereas high α-stereoselectivity was realized under low concentration conditions.

Target-selective photo-degradation of AFP-L3 and selective photo-cytotoxicity against HuH-7 hepatocarcinoma cells using an anthraquinone–PhoSL hybrid

Co-reporter:Mai Okuyama, Haruna Ueno, Yuka Kobayashi, Hirokazu Kawagishi, Daisuke Takahashi and Kazunobu Toshima

Chemical Communications 2016 vol. 52(Issue 10) pp:2169-2172

Publication Date(Web):14 Dec 2015

DOI:10.1039/C5CC09542E

A purposefully-designed anthraquinone–Pholiota squarrosa lectin (PhoSL) hybrid effectively degraded α-fetoprotein-L3 (AFP-L3) associated with liver cancer. Degradation was achieved under light irradiation in the absence of any additives and under neutral pH conditions. Moreover, the hybrid effectively exhibited selective photo-cytotoxicity against HuH-7 hepatocarcinoma cells upon photo-irradiation.

Glycosyl-Acceptor-Derived Borinic Ester-Promoted Direct and β-Stereoselective Mannosylation with a 1,2-Anhydromannose Donor

Co-reporter:Masamichi Tanaka, Junki Nashida, Daisuke Takahashi, and Kazunobu Toshima

Organic Letters 2016 Volume 18(Issue 9) pp:2288-2291

Publication Date(Web):April 19, 2016

DOI:10.1021/acs.orglett.6b00926

β-Stereoselective mannosylations were conducted using a 1,2-anhydromannose donor and mono-ol acceptors in the presence of a glycosyl-acceptor-derived borinic ester. Reactions proceeded smoothly under mild conditions to provide the corresponding β-mannosides with high stereoselectivity in moderate to high yields. In addition, the present glycosylation method was applied successfully to the total synthesis of acremomannolipin A.

Target-selective photo-degradation of a sialyl Lewis a (sLea) conjugate and photo-cytotoxicity against sLea positive cancer cells using an anthraquinone-antibody hybrid

Co-reporter:Daisuke Takahashi, Takashi Nagao, Shota Sotokawa and Kazunobu Toshima

MedChemComm 2016 vol. 7(Issue 6) pp:1224-1228

Publication Date(Web):11 May 2016

DOI:10.1039/C6MD00167J

A purpose-designed anthraquinone–monoclonal antibody (anti-sialyl Lewis A (sLea) mAb) hybrid 6 selectively bound to and effectively degraded the target glycoprotein, HSA (human serum albumin)–sLea conjugate 4. Degradation was achieved using long wavelength UV light irradiation in the absence of any additives and under neutral conditions. Furthermore, the hybrid 6 exhibited selective photo-cytotoxicity against the sLea positive cancer cells A431 and WiDr cells only upon photo-irradiation.

Systematic synthesis of low-molecular weight fucoidan derivatives and their effect on cancer cells

Co-reporter:Akihiro Kasai, Shinsuke Arafuka, Nozomi Koshiba, Daisuke Takahashi and Kazunobu Toshima

Organic & Biomolecular Chemistry 2015 vol. 13(Issue 42) pp:10556-10568

Publication Date(Web):26 Aug 2015

DOI:10.1039/C5OB01634G

Low-molecular weight type I and II fucoidan derivatives with different sulfation patterns were designed and systematically synthesized from the corresponding common key intermediate and their anti-proliferative activities and apoptosis-inducing activities against human breast cancer (MCF-7) and human cervical epithelioid carcinoma (HeLa) cells were evaluated. Our results demonstrated that one of the type II fucoidan derivatives, 9, effectively reduced the number of viable MCF-7 and HeLa cells in a dose-dependent manner without causing cytotoxicity toward normal WI-38 cells, and that the anti-proliferative activity of 9 was comparable to that of fucoidan 2 isolated from Fucus vesiculosus. Moreover, it was found that both 2 and 9 exhibited similar apoptosis-inducing activities through activation of caspase-8 and -9 on MCF-7 and HeLa cells, respectively.

Glycosylations of Glycals using N-Iodosuccinimide (NIS) and Phosphorus Compounds for Syntheses of 2-Iodo- and 2-Deoxyglycosides

Co-reporter:Tomoya Kimura, Daisuke Takahashi, and Kazunobu Toshima

The Journal of Organic Chemistry 2015 Volume 80(Issue 19) pp:9552-9562

Publication Date(Web):September 16, 2015

DOI:10.1021/acs.joc.5b01542

The glycosylations of glycals and alcohols using N-iodosuccinimide (NIS) and a catalytic amount of PPh3 effectively proceeded under mild conditions to provide the corresponding 2-deoxy-2-iodoglycosides in high yields. The reactivity of the iodoglycosylations with PPh3 significantly increased in comparison to that using NIS alone as an activator. In addition, the glycosylations of glycals and alcohols using catalytic amounts of NIS and P(OPh)3 were effectively realized to give the corresponding 2-deoxyglycosides in high yields.

Chemical approach for target-selective degradation of oligosaccharides using photoactivatable organic molecules

Co-reporter:Kazunobu Toshima;Daisuke Takahashi

Glycoconjugate Journal 2015 Volume 32( Issue 7) pp:475-482

Publication Date(Web):2015 October

DOI:10.1007/s10719-015-9591-9

Molecular design, chemical synthesis, and biological evaluation of several organic molecules, which can target-selectively photodegrade oligosaccharides by irradiation with a specific wavelength of light under mild conditions without any additives, are introduced. These novel class of photochemical agents promise bright prospects for finding not only molecular-targeted bioprobes for understanding of the structure-activity relationships of oligosaccharides but also novel therapeutic drugs targeting biologically important oligosaccharides.

Systematic synthesis of sulfated oligofucosides and their effect on breast cancer MCF-7 cells

Co-reporter:Shinsuke Arafuka, Nozomi Koshiba, Daisuke Takahashi and Kazunobu Toshima

Chemical Communications 2014 vol. 50(Issue 69) pp:9831-9834

Publication Date(Web):09 Jun 2014

DOI:10.1039/C4CC03544E

Sulfated tetrafucosides 2–5 with different sulfation patterns, and a non-sulfated tetrafucoside 6, were designed and systematically synthesized from the common key intermediate 12. In addition, their anti-proliferative activities and apoptosis-inducing activities against human breast cancer MCF-7 cells were evaluated. Our results demonstrated that the sulfated tetrafucosides 2–4 reduced the number of MCF-7 cells in a dose-dependent manner, and of these, 3,4-O-sulfated type 4 showed the highest anti-proliferative activity, comparable to the activity of fucoidan 1 isolated from Fucus vesiculosus. Furthermore, it was revealed that both 1 and 4 exhibited apoptosis-inducing activities through activation of caspase-8 on MCF-7 cells.

A solid-phase affinity labeling method for target-selective isolation and modification of proteins

Co-reporter:Daichi Kuwahara, Takahiro Hasumi, Hajime Kaneko, Madoka Unno, Daisuke Takahashi and Kazunobu Toshima

Chemical Communications 2014 vol. 50(Issue 98) pp:15601-15604

Publication Date(Web):23 Oct 2014

DOI:10.1039/C4CC06783E

Solid-phase affinity labeling of a target protein, peanut agglutinin (PNA), with the specifically designed chemical tool 1 selectively and effectively furnished the labeled PNA. Furthermore, this method was applicable to native human carbonic anhydrase II in red blood cell lysate using the chemical tool 2 without the need for tedious manipulations.

Photodegradation of amyloid β and reduction of its cytotoxicity to PC12 cells using porphyrin derivatives

Co-reporter:Ayumi Hirabayashi, Yutaka Shindo, Kotaro Oka, Daisuke Takahashi and Kazunobu Toshima

Chemical Communications 2014 vol. 50(Issue 67) pp:9543-9546

Publication Date(Web):07 Jul 2014

DOI:10.1039/C4CC03791J

A purpose-designed porphyrin–peptide hybrid effectively degraded amyloid β monomer and oligomers associated with Alzheimer's disease. Degradation was achieved using light irradiation in the absence of any additives and under neutral conditions. Moreover, the hybrid effectively neutralized the cytotoxicity of amyloid β in PC12 cells upon photoirradiation.

Photo-induced glycosylation using reusable organophotoacids

Co-reporter:Ryosuke Iwata, Kanjiro Uda, Daisuke Takahashi and Kazunobu Toshima

Chemical Communications 2014 vol. 50(Issue 73) pp:10695-10698

Publication Date(Web):24 Jul 2014

DOI:10.1039/C4CC04753B

The glycosylation reactions of glycosyl trichloroacetimidates and several alcohols using an organophotoacid as an activator under photoirradiation proceeded smoothly to give the corresponding glycosides in high yields. The organophotoacid was recovered and reused without any loss of efficiency.

Chemical and biological evaluation of unusual sugars, α-aculosides, as novel Michael acceptors

Co-reporter:Hiromasa Ikeda, Erika Kaneko, Shunsuke Okuzawa, Daisuke Takahashi and Kazunobu Toshima

Organic & Biomolecular Chemistry 2014 vol. 12(Issue 44) pp:8832-8835

Publication Date(Web):18 Sep 2014

DOI:10.1039/C4OB01877J

The unusual sugars, α-aculosides, which appear in certain antibiotics and have an α,β-unsaturated ketone structure, were found to be novel and selective Michael acceptors for the thiol function of cysteine residues. A coumarin derivative possessing α-aculoside as a Michael acceptor effectively and irreversibly operated as a fluorescent probe in cells. Furthermore, α-aculosides exhibited cytotoxic activity against several cancer cell lines.

Total Synthesis of Vineomycin B2

Co-reporter:Shunichi Kusumi ; Satoshi Tomono ; Shunsuke Okuzawa ; Erika Kaneko ; Takashi Ueda ; Kaname Sasaki ; Daisuke Takahashi

Journal of the American Chemical Society 2013 Volume 135(Issue 42) pp:15909-15912

Publication Date(Web):September 27, 2013

DOI:10.1021/ja407827n

The first total synthesis of vineomycin B2 (1) has been accomplished. The aglycon segment, a vineomycinone B2 derivative, and the glycon segment, an α-l-acurosyl-l-rhodinose derivative, were prepared via C-glycosylation using an unprotected sugar and powerful chemoselective O-glycosylation using a 2,3-unsaturated sugar, respectively, as the key steps. Furthermore, effective and simultaneous introduction of the two glycon moieties to the aglycon part by concentration-controlled glycosylation led to the total synthesis of 1.

Photodegradation and inhibition of drug-resistant influenza virus neuraminidase using anthraquinone–sialic acid hybrids

Co-reporter:Yusuke Aoki, Shuho Tanimoto, Daisuke Takahashi and Kazunobu Toshima

Chemical Communications 2013 vol. 49(Issue 12) pp:1169-1171

Publication Date(Web):18 Dec 2012

DOI:10.1039/C2CC38742E

The anthraquinone–sialic acid hybrids designed effectively degraded not only non-drug-resistant neuraminidase but also drug-resistant neuraminidase, which is an important target of anti-influenza therapy. Degradation was achieved using long-wavelength UV radiation in the absence of any additives and under neutral conditions. Moreover, the hybrids efficiently inhibited neuraminidase activities upon photo-irradiation.

Design, synthesis and evaluation of a boronic acid based artificial receptor for L-DOPA in aqueous media

Co-reporter:Haruna Ueno, Takayuki Iwata, Nozomi Koshiba, Daisuke Takahashi and Kazunobu Toshima

Chemical Communications 2013 vol. 49(Issue 88) pp:10403-10405

Publication Date(Web):17 Sep 2013

DOI:10.1039/C3CC45275A

Design and synthesis of a boronic acid based artificial receptor which selectively and effectively bound to a neurotransmitter, L-DOPA (1), in aqueous media. In addition, the synthetic receptor was found to effectively inhibit the DDC (L-DOPA decarboxylase) enzymatic reaction under physiological conditions.

Target-selective photo-degradation of verotoxin-1 and reduction of its cytotoxicity to Vero cells using porphyrin–globotriose hybrids

Co-reporter:Atsushi Okochi, Shuho Tanimoto, Daisuke Takahashi and Kazunobu Toshima

Chemical Communications 2013 vol. 49(Issue 54) pp:6027-6029

Publication Date(Web):17 May 2013

DOI:10.1039/C3CC42957A

Designed and synthesized porphyrin–globotriose hybrids effectively degraded verotoxin-1, which causes severe bloody diarrhoea and fetal hemolytic uremic syndrome (HUS). Degradation was achieved using long-wavelength UV or visible light irradiation in the absence of any additives and under neutral conditions. Moreover, the hybrids neutralized the cytotoxicity of verotoxin upon photo-irradiation.

Light-induced O-glycosylation of unprotected deoxythioglycosyl donors

Co-reporter:Mayuka Nakanishi, Daisuke Takahashi and Kazunobu Toshima

Organic & Biomolecular Chemistry 2013 vol. 11(Issue 31) pp:5079-5082

Publication Date(Web):21 Jun 2013

DOI:10.1039/C3OB41143E

The O-glycosylation of several unprotected deoxythioglycosides and alcohols using 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) under long-wavelength UV irradiation was effectively realized using a single electron transfer (SET) mechanism. In some cases, the use of p-methoxyboronic acid was very effective in temporary protection of the 1,3-diol (C4 and C6 positions) of the unprotected glycosyl donors to increase the yields of the obtained O-glycosides.

The direct and one-pot transformation of xylan into the biodegradable surfactants, alkyl xylosides, is aided by an ionic liquid

Co-reporter:Maiko Sekine, Tomoya Kimura, Yasushi Katayama, Daisuke Takahashi and Kazunobu Toshima

RSC Advances 2013 vol. 3(Issue 43) pp:19756-19759

Publication Date(Web):12 Aug 2013

DOI:10.1039/C3RA42680G

Xylan, the most abundant and renewable hemicellulose, was directly converted in one step into alkyl xylosides, a family of biodegradable surfactants, using fatty alcohols and catalytic amounts of 10-camphorsulfonic acid (CSA) in an ionic liquid, 1-n-butyl-3-methylimidazolium chloride (Bmim[Cl]).

Chemical biology based on target-selective degradation of proteins and carbohydrates using light-activatable organic molecules

Co-reporter:Kazunobu Toshima

Molecular BioSystems 2013 vol. 9(Issue 5) pp:834-854

Publication Date(Web):30 Nov 2012

DOI:10.1039/C2MB25416F

Proteins and carbohydrates play crucial roles in a wide range of biological processes, including serious diseases. The development of novel and innovative methods for selective control of specific proteins and carbohydrates functions has attracted much attention in the field of chemical biology. In this account article, the development of novel chemical tools, which can degrade target proteins and carbohydrates by irradiation with a specific wavelength of light under mild conditions without any additives, is introduced. This novel class of photochemical agents promise bright prospects for finding not only molecular-targeted bioprobes for understanding of the structure–activity relationships of proteins and carbohydrates but also novel therapeutic drugs targeting proteins and carbohydrates.

Chiral Brnsted Acid Mediated Glycosylation with Recognition of Alcohol Chirality

Co-reporter:Tomoya Kimura;Maiko Sekine;Dr. Daisuke Takahashi ;Dr. Kazunobu Toshima

Angewandte Chemie International Edition 2013 Volume 52( Issue 46) pp:12131-12134

Publication Date(Web):

DOI:10.1002/anie.201304830

Improved total synthesis of incednam

Co-reporter:Akira Takada, Kanjiro Uda, Takashi Ohtani, Shinya Tsukamoto, Daisuke Takahashi and Kazunobu Toshima

The Journal of Antibiotics 2013 66(3) pp:155-159

Publication Date(Web):February 6, 2013

DOI:10.1038/ja.2013.4

An alternative and improved total synthesis of incednam, the aglycon of the 24-membered macrolactam glycoside antibiotic incednine, was accomplished. The synthesis was realized via construction of the 24-membered macrocycle using intramolecular ring-closing olefin metathesis reaction as a key step.

Chiral Brnsted Acid Mediated Glycosylation with Recognition of Alcohol Chirality

Co-reporter:Tomoya Kimura;Maiko Sekine;Dr. Daisuke Takahashi ;Dr. Kazunobu Toshima

Angewandte Chemie 2013 Volume 125( Issue 46) pp:12353-12356

Publication Date(Web):

DOI:10.1002/ange.201304830

Photodegradation of lipopolysaccharides and the inhibition of macrophage activation by anthraquinone–boronic acid hybrids

Co-reporter:Daisuke Takahashi, Takuya Miura and Kazunobu Toshima

Chemical Communications 2012 vol. 48(Issue 61) pp:7595-7597

Publication Date(Web):13 Jun 2012

DOI:10.1039/C2CC33559J

Target-selective photodegradation of 3-deoxy-D-manno-2-octulopyranosonic acid (KDO) was achieved without additives and under neutral conditions using a designed anthraquinone–boronic acid hybrid and long wavelength UV light irradiation. The hybrid can photodegrade lipopolysaccharides (LPS) and inhibit macrophage activation induced by LPS.

Chemical methods for degradation of target oligosaccharides using designed light-activatable organic molecules

Co-reporter:Daisuke Takahashi and Kazunobu Toshima

Chemical Communications 2012 vol. 48(Issue 37) pp:4397-4407

Publication Date(Web):14 Feb 2012

DOI:10.1039/C2CC17384K

Carbohydrates play crucial roles in a wide range of biological processes, including serious diseases. The development of novel and innovative methods for selective control of specific oligosaccharide functions has attracted much attention in the fields of chemistry, biology, and medicine. In this feature article, the development of novel chemical tools, which can degrade target oligosaccharides by irradiation with a specific wavelength of light under mild conditions without any additives, is introduced. This novel class of photochemical agents promise bright prospects for finding not only molecular-targeted bioprobes for understanding of the structure–activity relationships of oligosaccharides but also novel therapeutic drugs targeting oligosaccharides.

Chemical methods for degradation of target proteins using designed light-activatable organic molecules

Co-reporter:Shuho Tanimoto, Daisuke Takahashi and Kazunobu Toshima

Chemical Communications 2012 vol. 48(Issue 62) pp:7659-7671

Publication Date(Web):22 May 2012

DOI:10.1039/C2CC30831B

Molecular design, chemical synthesis, and biological evaluation of several designed organic molecules, which target-selectively degrade proteins upon photo-irradiation, are introduced. The designed molecules for protein photo-degradation include 2-phenylquinoline–steroid hormone hybrids and porphyrin derivatives, both of which selectively photo-degrade estrogen receptor-α, and fullerene–sugar and –sulfonic acid hybrids, which selectively photo-degrade HIV-1 protease and amyloid β, respectively. The information will provide a novel and effective way to control specific functions of proteins, and contribute to the molecular design of novel protein photo-degrading agents, which should find wide application in chemistry, biology, and medicine.

Carbohydrate recognition and photodegradation by an anthracene–Kemp's acid hybrid

Co-reporter:Miyuki Nishibu, Daisuke Takahashi and Kazunobu Toshima

Organic & Biomolecular Chemistry 2012 vol. 10(Issue 42) pp:8393-8395

Publication Date(Web):19 Sep 2012

DOI:10.1039/C2OB26417J

Selective recognition and photodegradation of a monosaccharide, octyl β-D-glucopyranoside, was achieved without any additives under neutral conditions using an anthracene–Kemp's acid hybrid and long-wavelength UV irradiation.

Target-Selective Photodegradation of HIV-1 Protease and Inhibition of HIV-1 Replication in Living Cells by Designed FullereneSugar Hybrids

Co-reporter:Shuho Tanimoto;Satoshi Sakai;Eriko Kudo;Dr. Seiji Okada;Dr. Shuichi Matsumura;Dr. Daisuke Takahashi;Dr. Kazunobu Toshima

Chemistry – An Asian Journal 2012 Volume 7( Issue 5) pp:911-914

Publication Date(Web):

DOI:10.1002/asia.201101043

Degradation of Target Oligosaccharides by AnthraquinoneLectin Hybrids with Light Switching

Co-reporter:Yukari Imai;Shingo Hirono;Haruka Matsuba;Dr. Tomohiro Suzuki;Dr. Yuka Kobayashi;Dr. Hirokazu Kawagishi;Dr. Daisuke Takahashi;Dr. Kazunobu Toshima

Chemistry – An Asian Journal 2012 Volume 7( Issue 1) pp:97-104

Publication Date(Web):

DOI:10.1002/asia.201100586

Abstract

Anthraquinone–lectin hybrids were effectively synthesized using water-soluble anthraquinone derivative 11 with concanavalin A (ConA) and hygrophorus russula lectin (HRL) to give anthraquinone–ConA (16) and anthraquinone–HRL (17) hybrids, respectively. These anthraquinone–lectin hybrids effectively and selectively degraded oligosaccharides containing a mannose residue as a non-reducing terminal sugar, which has affinity for ConA and HRL, under photo-irradiation with long-wavelength UV light without additives and under neutral conditions. In addition, anthraquinone–HRL (17) selectively photo-degraded only Man(α1,6)Man, which has a high affinity for HRL, among several mannosides by recognition of both the type and glycosidic linkage profile of the sugar in an oligosaccharide.

Target-selective photodegradation of oligosaccharides by a fullerene–boronic acid hybrid upon visible light irradiation

Co-reporter:Daisuke Takahashi, Shingo Hirono and Kazunobu Toshima

Chemical Communications 2011 vol. 47(Issue 42) pp:11712-11714

Publication Date(Web):27 Sep 2011

DOI:10.1039/C1CC15646B

A fullerene derivative was found to be capable of photodegrading oligosaccharides under irradiation with not only UV but also visible light. Furthermore, target-selective photodegradation of oligosaccharides (β-D-galactofuranosides) was achieved by a designed and synthesized fullerene–boronic acid hybrid upon irradiation with visible light in the absence of any additives under neutral conditions.

Armed–disarmed effect of remote protecting groups on the glycosylation reaction of 2,3-dideoxyglycosyl donors

Co-reporter:Satoshi Tomono, Shunichi Kusumi, Daisuke Takahashi, Kazunobu Toshima

Tetrahedron Letters 2011 Volume 52(Issue 18) pp:2399-2403

Publication Date(Web):4 May 2011

DOI:10.1016/j.tetlet.2011.02.109

The armed–disarmed effect of remote protecting groups at the C-4 and/or C-6 position(s) on the glycosylation reactions of 2,3-dideoxyglycosyl donors was investigated. It was found that under various glycosylation conditions, 4- or 6-O-Bn 2,3-dideoxyglycosyl donors were much more reactive than the corresponding 4,6-di-O-Bz 2,3-dideoxyglycosyl donors. Based on these results, an effective and chemoselective glycosylation reaction using 4,6-di-O-Bn glycosyl acetate and 4-OH-6-O-Bz glycosyl acetate was realized, producing a 2,3-dideoxydisaccharide in good yield with high α-stereoselectivity.

Inhibition of Amyloid Aggregation and Cytotoxicity by Photodegradation Using a Designed Fullerene Derivative

Co-reporter:Yasunori Ishida;Tomohiko Fujii;Dr. Kotaro Oka;Dr. Daisuke Takahashi;Dr. Kazunobu Toshima

Chemistry – An Asian Journal 2011 Volume 6( Issue 9) pp:2312-2315

Publication Date(Web):

DOI:10.1002/asia.201100421

Total Synthesis of Incednam, the Aglycon of Incednine

Co-reporter:Takashi Ohtani, Shinya Tsukamoto, Hiroshi Kanda, Kensuke Misawa, Yoshifumi Urakawa, Takahiro Fujimaki, Masaya Imoto, Yoshikazu Takahashi, Daisuke Takahashi, and Kazunobu Toshima

Organic Letters 2010 Volume 12(Issue 21) pp:5068-5071

Publication Date(Web):October 12, 2010

DOI:10.1021/ol102400c

The first total synthesis of incednam (1), the aglycon of antibiotic incednine (2), is described. Incednine has been reported to exhibit significant inhibitory activity against the antiapoptotic oncoproteins Bcl-2 and Bcl-xL. The synthesis of 1 commenced with the preparation of the C1−C13 subunit 3 and the C14−C23 subunit 4. The construction of the novel 24-membered macrocycle was achieved by the application of a Stille coupling between 3 and 4, followed by macrolactamization.

Chemoselective glycosylations using 2,3-unsaturated-4-keto glycosyl donors

Co-reporter:Shunichi Kusumi, Sainan Wang, Tatsuya Watanabe, Kaname Sasaki, Daisuke Takahashi and Kazunobu Toshima

Organic & Biomolecular Chemistry 2010 vol. 8(Issue 5) pp:988-990

Publication Date(Web):07 Jan 2010

DOI:10.1039/B925587G

2,3-Unsaturated-4-keto glycosyl acetates were found to exhibit low reactivity under several glycosylation conditions. Chemoselective glycosylations were effectively performed using 2,3-unsaturated glycosyl and 2,3-dideoxy glycosyl acetates as armed glycosyl donors, and 2,3-unsaturated-4-keto glycosyl acetates as disarmed glycosyl donors.

Effective and chemoselective glycosylations using 2,3-unsaturated sugars

Co-reporter:Shunichi Kusumi, Kaname Sasaki, Sainan Wang, Tatsuya Watanabe, Daisuke Takahashi and Kazunobu Toshima

Organic & Biomolecular Chemistry 2010 vol. 8(Issue 14) pp:3164-3178

Publication Date(Web):26 May 2010

DOI:10.1039/C004204H

Glycosyl donors containing a double bond between C2 and C3 were designed by mimicking the reaction mechanism of lysozyme-initiated hydrolysis of mucopolysaccharides. It was found that, under various glycosylation conditions, the reactivities of 2,3-unsaturated glycosyl acetates were significantly higher, while those of the corresponding 2,3-unsaturated-4-keto glycosyl acetates were much lower than those of the corresponding 2,3-dideoxy (2,3-saturated) glycosyl acetates. Based on these results, chemoselective glycosylations were effectively realized via combinatorial techniques in short-steps using three types of glycosyl donors to construct several types of deoxyoligosaccharides. Furthermore, the highly reactive 2,3-unsaturated glycosyl acetates were found to be useful in the synthesis of the O-glycosides of low reactive tertiary alcohols.

Photo-degradation of amyloid β by a designed fullerene–sugar hybrid

Co-reporter:Yasunori Ishida, Shuho Tanimoto, Daisuke Takahashi and Kazunobu Toshima

MedChemComm 2010 vol. 1(Issue 3) pp:212-215

Publication Date(Web):04 Aug 2010

DOI:10.1039/C0MD00075B

A purpose-designed fullerene–sugar hybrid effectively inhibited amyloid β peptide aggregation and caused degradation of its monomer and oligomers, which are key compounds in Alzheimer's disease. Degradation was achieved using long-wavelength UV radiation in the absence of any additives and under neutral conditions.

A novel glycosylation of inactive glycosyl donors using an ionic liquid containing a protic acid under reduced pressure conditions

Co-reporter:Yasutaka Kuroiwa, Maiko Sekine, Satoshi Tomono, Daisuke Takahashi, Kazunobu Toshima

Tetrahedron Letters 2010 Volume 51(Issue 48) pp:6294-6297

Publication Date(Web):1 December 2010

DOI:10.1016/j.tetlet.2010.09.108

The glycosylation of inactive glycosyl donors, such as methyl glycosides and 1-hydroxy sugars with nearly stoichiometric amounts of various alcohols (1.1 equiv) in an ionic liquid containing a protic acid (acid-IL) under reduced pressure conditions proceeded effectively to give the corresponding glycosides in good to high yields. Furthermore, the acid-IL could be reused for additional glycosylations without the loss of efficiency.

Photodegradation of Target Oligosaccharides by Light-Activated Small Molecules

Co-reporter:Dr. Daisuke Takahashi;Shingo Hirono;Chigusa Hayashi;Dr. Masayuki Igarashi;Dr. Yoshio Nishimura;Dr. Kazunobu Toshima

Angewandte Chemie International Edition 2010 Volume 49( Issue 52) pp:10096-10100

Publication Date(Web):

DOI:10.1002/anie.201005161

Photodegradation of Target Oligosaccharides by Light-Activated Small Molecules

Co-reporter:Dr. Daisuke Takahashi;Shingo Hirono;Chigusa Hayashi;Dr. Masayuki Igarashi;Dr. Yoshio Nishimura;Dr. Kazunobu Toshima

Angewandte Chemie 2010 Volume 122( Issue 52) pp:10294-10298

Publication Date(Web):

DOI:10.1002/ange.201005161

Synthetic studies of incednine: synthesis of C1–C13 pentaenoic acid segment

Co-reporter:Takashi Ohtani, Hiroshi Kanda, Kensuke Misawa, Yoshifumi Urakawa, Kazunobu Toshima

Tetrahedron Letters 2009 50(19) pp: 2270-2273

Publication Date(Web):

DOI:10.1016/j.tetlet.2009.02.203

Target-selective photo-degradation of HIV-1 protease by a fullerene-sugar hybrid

Co-reporter:Shuho Tanimoto, Satoshi Sakai, Shuichi Matsumura, Daisuke Takahashi and Kazunobu Toshima

Chemical Communications 2008 (Issue 44) pp:5767-5769

Publication Date(Web):02 Oct 2008

DOI:10.1039/B811726H

A designed fullerene-sugar hybrid effectively and selectively degraded the target protein, HIV-1 protease, which has high affinity for the fullerene moiety; degradation was achieved using long-wavelength UV or visible photo-irradiation, in the absence of any additives and under neutral conditions.

Target-selective degradation of proteins by porphyrins upon visible photo-irradiation

Co-reporter:Shuho Tanimoto, Shuichi Matsumura and Kazunobu Toshima

Chemical Communications 2008 (Issue 31) pp:3678-3680

Publication Date(Web):11 Jun 2008

DOI:10.1039/B806961A

A porphyrin derivative effectively and selectively degraded the target transcription factor, human estrogen receptor-α (hER-α), upon visible light irradiation, in the absence of additives and under neutral conditions.

Target-selective degradation of proteins by a light-activated 2-phenylquinoline-estradiol hybrid

Co-reporter:Akane Suzuki, Kana Tsumura, Takeo Tsuzuki, Shuichi Matsumura and Kazunobu Toshima

Chemical Communications 2007 (Issue 41) pp:4260-4262

Publication Date(Web):10 Aug 2007

DOI:10.1039/B708947C

A designed 2-phenylquinoline-estradiol hybrid effectively and selectively degraded the target transcription factor, human estrogen receptor-α (hER-α), which has a high affinity with the estradiol moiety, under long-wavelength UV photo-irradiation, without additives and under neutral conditions.

Target-Selective Degradation of Oligosaccharides by a Light-Activated Small-Molecule–Lectin Hybrid

Co-reporter:Maiko Ishii;Shuichi Matsumura Dr. Dr.

Angewandte Chemie 2007 Volume 119(Issue 44) pp:

Publication Date(Web):26 SEP 2007

DOI:10.1002/ange.200702127

Der Abbau von Oligosacchariden, die für eine Zielstruktur selektiv sind, wird in einer neuartigen Methode durch ein photoaktivierbares Anthrachinon-Lectin-Hybridmolekül bewirkt (siehe Schema). Die Reaktion läuft unter neutralen Bedingungen ohne Zusatz von Additiven ab. PNA=Erdnuss-Agglutinin.

Target-Selective Degradation of Oligosaccharides by a Light-Activated Small-Molecule–Lectin Hybrid

Co-reporter:Maiko Ishii;Shuichi Matsumura Dr. Dr.

Angewandte Chemie International Edition 2007 Volume 46(Issue 44) pp:

Publication Date(Web):26 SEP 2007

DOI:10.1002/anie.200702127

An innovative method for target-selective degradation of oligosaccharides induced by a light-activated hybrid molecule consisting of anthraquinone and lectin has been developed (see scheme). The reaction takes place under neutral conditions, and no additives are required. PNA=peanut agglutinin.

A highly stereoselective synthesis of β-olivosides by glycosidations of 2-iodo-olivosyl fluoride using montmorillonite K-10 as an environmentally benign solid acid

Co-reporter:Kazunobu Toshima, Keizou Uehara, Hideyuki Nagai and Shuichi Matsumura

Green Chemistry 2002 vol. 4(Issue 1) pp:27-29

Publication Date(Web):14 Jan 2002

DOI:10.1039/B109172G

The novel and highly β-stereoselective glycosidations of a 2-iodo-olivosyl fluoride and alcohols using a heterogeneous and environmentally benign solid acid, montmorillonite K-10, have been developed to afford the corresponding 2-iodo-β-olivosides in high yields with high stereoselectivities.

Molecular design and evaluation of quinoxaline-carbohydrate hybrids as novel and efficient photo-induced GG-selective DNA cleaving agents

Co-reporter:Kazunobu Toshima, Ryusuke Takano, Tomohiro Ozawa and Shuichi Matsumura

Chemical Communications 2002 (Issue 3) pp:212-213

Publication Date(Web):08 Jan 2002

DOI:10.1039/B107829C

Quinoxaline, found in antitumor quinoxaline antibiotics, was found to cleave double stranded DNA at the 5′ side guanine of 5′-GG-3′ site on irradiation with long wavelength UV light without any additive; furthermore, a bis(quinoxaline–carbohydrate) hybrid system was very effective for DNA cleavage.

Vacuolar-type H+-ATPase inhibitory activity of synthetic analogues of the concanamycins: Is the hydrogen bond network involving the lactone carbonyl, the hemiacetal hydroxy group, and the C-19 hydroxy group essential for the biological activity of the concanamycins?

Co-reporter:Yuya Yoshimoto, Takaaki Jyojima, Tsuyoshi Arita, Minoru Ueda, Masaya Imoto, Shuichi Matsumura, Kazunobu Toshima

Bioorganic & Medicinal Chemistry Letters 2002 Volume 12(Issue 24) pp:3525-3528

Publication Date(Web):16 December 2002

DOI:10.1016/S0960-894X(02)00806-5

Synthetic analogue of the concanamycins, which lacks the hydrogen bond network existing in the concanamycin structure, retains vacuolar-type H+-ATPase (V-ATPase) inhibitory activity and induces apoptosis to cancer cells that overexpressing epidermal growth factor receptors (EGFR).Graphic

Carbohydrate-modulated DNA photocleavage: design, synthesis, and evaluation of novel glycosyl anthraquinones

Co-reporter:Kazunobu Toshima, Yutaka Maeda, Hiromi Ouchi, Akira Asai, Shuichi Matsumura

Bioorganic & Medicinal Chemistry Letters 2000 Volume 10(Issue 19) pp:2163-2165

Publication Date(Web):2 October 2000

DOI:10.1016/S0960-894X(00)00410-8

Novel and artificial anthraquinone-carbohydrate hybrids were designed and synthesized, and found to effectively cleave DNA under irradiation with a long wavelength UV light and also exhibit cytotoxicity against HeLa S3 cells.

Chemical Synthesis and DNA Photocleavage of the Intercalator–Carbohydrate Hybrid Moiety of the Neocarzinostatin Chromophore

Co-reporter:Kazunobu Toshima Dr.;Shigeki Takai;Yutaka Maeda;Ryusuke Takano;Shuichi Matsumura Dr.

Angewandte Chemie 2000 Volume 112(Issue 20) pp:

Publication Date(Web):13 OCT 2000

DOI:10.1002/1521-3757(20001016)112:20<3802::AID-ANGE3802>3.0.CO;2-L

2-Phenylquinoline–Carbohydrate Hybrids: Molecular Design, Chemical Synthesis, and Evaluation of a New Family of Light-Activatable DNA-Cleaving Agents

Co-reporter:Kazunobu Toshima;Ryusuke Takano;Yutaka Maeda;Masataka Suzuki;Akira Asai;Shuichi Matsumura

Angewandte Chemie International Edition 1999 Volume 38(Issue 24) pp:

Publication Date(Web):16 DEC 1999

DOI:10.1002/(SICI)1521-3773(19991216)38:24<3733::AID-ANIE3733>3.0.CO;2-W

Artificial intercalator–carbohydrate hybrids such as that shown in the scheme cleave DNA at the site of guanine on irradiation with UV light with a long wavelength. The hybrids also exhibit strong cytotoxicity when irradiated. The hybrid system is very important for DNA cleavage, and the cytotoxic activity correlates with the DNA-cleaving capacity

2-Phenylchinolin-Kohlenhydrat-Hybride: Moleküldesign, Synthese und Prüfung einer neuen Klasse von photoaktivierbaren DNA-spaltenden Substanzen

Co-reporter:Kazunobu Toshima;Ryusuke Takano;Yutaka Maeda;Masataka Suzuki;Akira Asai;Shuichi Matsumura

Angewandte Chemie 1999 Volume 111(Issue 24) pp:

Publication Date(Web):16 DEC 1999

DOI:10.1002/(SICI)1521-3757(19991216)111:24<3953::AID-ANGE3953>3.0.CO;2-4

Künstliche Intercalator-Kohlenhydrat-Hybride wie das gezeigte spalten DNA bei Bestrahlung mit langwelligem UV-Licht an den Guaninresten. Bei Bestrahlung zeigen die Hybride auch starke Cytotoxizität. Die Hybridanordnung ist wichtig für die DNA-Spaltung (die einzelnen Komponenten, Didesoxyaminozucker oder 2-Phenylchinolin, zeigen keine DNA-Spaltung), und die cytotoxische Aktivität korreliert mit der Fähigkeit, DNA zu spalten.

Target-selective photo-degradation of HIV-1 protease by a fullerene-sugar hybrid

Co-reporter:Shuho Tanimoto, Satoshi Sakai, Shuichi Matsumura, Daisuke Takahashi and Kazunobu Toshima

Chemical Communications 2008(Issue 44) pp:NaN5769-5769

Publication Date(Web):2008/10/02

DOI:10.1039/B811726H

A designed fullerene-sugar hybrid effectively and selectively degraded the target protein, HIV-1 protease, which has high affinity for the fullerene moiety; degradation was achieved using long-wavelength UV or visible photo-irradiation, in the absence of any additives and under neutral conditions.

Regio- and stereoselective β-mannosylation using a boronic acid catalyst and its application in the synthesis of a tetrasaccharide repeating unit of lipopolysaccharide derived from E. coli O75

Co-reporter:Nobuya Nishi, Junki Nashida, Eisuke Kaji, Daisuke Takahashi and Kazunobu Toshima

Chemical Communications 2017 - vol. 53(Issue 21) pp:NaN3021-3021

Publication Date(Web):2017/02/20

DOI:10.1039/C7CC00269F

Regio- and stereoselective β-mannosylations using 1,2-anhydromannose and diol sugar acceptors in the presence of a boronic acid catalyst proceeded smoothly to give the corresponding β-mannosides with high regio- and β-stereoselectivities in high yields without further additives under mild conditions. In addition, this glycosylation method was applied successfully to the synthesis of a tetrasaccharide repeating unit of lipopolysaccharide (LPS) derived from E. coli O75.

Target-selective degradation of proteins by a light-activated 2-phenylquinoline-estradiol hybrid

Co-reporter:Akane Suzuki, Kana Tsumura, Takeo Tsuzuki, Shuichi Matsumura and Kazunobu Toshima

Chemical Communications 2007(Issue 41) pp:NaN4262-4262

Publication Date(Web):2007/08/10

DOI:10.1039/B708947C

A designed 2-phenylquinoline-estradiol hybrid effectively and selectively degraded the target transcription factor, human estrogen receptor-α (hER-α), which has a high affinity with the estradiol moiety, under long-wavelength UV photo-irradiation, without additives and under neutral conditions.

Effective and chemoselective glycosylations using 2,3-unsaturated sugars

Co-reporter:Shunichi Kusumi, Kaname Sasaki, Sainan Wang, Tatsuya Watanabe, Daisuke Takahashi and Kazunobu Toshima

Organic & Biomolecular Chemistry 2010 - vol. 8(Issue 14) pp:NaN3178-3178

Publication Date(Web):2010/05/26

DOI:10.1039/C004204H

Glycosyl donors containing a double bond between C2 and C3 were designed by mimicking the reaction mechanism of lysozyme-initiated hydrolysis of mucopolysaccharides. It was found that, under various glycosylation conditions, the reactivities of 2,3-unsaturated glycosyl acetates were significantly higher, while those of the corresponding 2,3-unsaturated-4-keto glycosyl acetates were much lower than those of the corresponding 2,3-dideoxy (2,3-saturated) glycosyl acetates. Based on these results, chemoselective glycosylations were effectively realized via combinatorial techniques in short-steps using three types of glycosyl donors to construct several types of deoxyoligosaccharides. Furthermore, the highly reactive 2,3-unsaturated glycosyl acetates were found to be useful in the synthesis of the O-glycosides of low reactive tertiary alcohols.

Carbohydrate recognition and photodegradation by an anthracene–Kemp's acid hybrid

Co-reporter:Miyuki Nishibu, Daisuke Takahashi and Kazunobu Toshima

Organic & Biomolecular Chemistry 2012 - vol. 10(Issue 42) pp:NaN8395-8395

Publication Date(Web):2012/09/19

DOI:10.1039/C2OB26417J

Selective recognition and photodegradation of a monosaccharide, octyl β-D-glucopyranoside, was achieved without any additives under neutral conditions using an anthracene–Kemp's acid hybrid and long-wavelength UV irradiation.

Target-selective degradation of proteins by porphyrins upon visible photo-irradiation

Co-reporter:Shuho Tanimoto, Shuichi Matsumura and Kazunobu Toshima

Chemical Communications 2008(Issue 31) pp:NaN3680-3680

Publication Date(Web):2008/06/11

DOI:10.1039/B806961A

A porphyrin derivative effectively and selectively degraded the target transcription factor, human estrogen receptor-α (hER-α), upon visible light irradiation, in the absence of additives and under neutral conditions.

Chemical methods for degradation of target proteins using designed light-activatable organic molecules

Co-reporter:Shuho Tanimoto, Daisuke Takahashi and Kazunobu Toshima

Chemical Communications 2012 - vol. 48(Issue 62) pp:NaN7671-7671

Publication Date(Web):2012/05/22

DOI:10.1039/C2CC30831B

Molecular design, chemical synthesis, and biological evaluation of several designed organic molecules, which target-selectively degrade proteins upon photo-irradiation, are introduced. The designed molecules for protein photo-degradation include 2-phenylquinoline–steroid hormone hybrids and porphyrin derivatives, both of which selectively photo-degrade estrogen receptor-α, and fullerene–sugar and –sulfonic acid hybrids, which selectively photo-degrade HIV-1 protease and amyloid β, respectively. The information will provide a novel and effective way to control specific functions of proteins, and contribute to the molecular design of novel protein photo-degrading agents, which should find wide application in chemistry, biology, and medicine.

Target-selective photo-degradation of verotoxin-1 and reduction of its cytotoxicity to Vero cells using porphyrin–globotriose hybrids

Co-reporter:Atsushi Okochi, Shuho Tanimoto, Daisuke Takahashi and Kazunobu Toshima

Chemical Communications 2013 - vol. 49(Issue 54) pp:NaN6029-6029

Publication Date(Web):2013/05/17

DOI:10.1039/C3CC42957A

Designed and synthesized porphyrin–globotriose hybrids effectively degraded verotoxin-1, which causes severe bloody diarrhoea and fetal hemolytic uremic syndrome (HUS). Degradation was achieved using long-wavelength UV or visible light irradiation in the absence of any additives and under neutral conditions. Moreover, the hybrids neutralized the cytotoxicity of verotoxin upon photo-irradiation.

Chemical and biological evaluation of unusual sugars, α-aculosides, as novel Michael acceptors

Co-reporter:Hiromasa Ikeda, Erika Kaneko, Shunsuke Okuzawa, Daisuke Takahashi and Kazunobu Toshima

Organic & Biomolecular Chemistry 2014 - vol. 12(Issue 44) pp:NaN8835-8835

Publication Date(Web):2014/09/18

DOI:10.1039/C4OB01877J

The unusual sugars, α-aculosides, which appear in certain antibiotics and have an α,β-unsaturated ketone structure, were found to be novel and selective Michael acceptors for the thiol function of cysteine residues. A coumarin derivative possessing α-aculoside as a Michael acceptor effectively and irreversibly operated as a fluorescent probe in cells. Furthermore, α-aculosides exhibited cytotoxic activity against several cancer cell lines.

Systematic synthesis of low-molecular weight fucoidan derivatives and their effect on cancer cells

Co-reporter:Akihiro Kasai, Shinsuke Arafuka, Nozomi Koshiba, Daisuke Takahashi and Kazunobu Toshima

Organic & Biomolecular Chemistry 2015 - vol. 13(Issue 42) pp:NaN10568-10568

Publication Date(Web):2015/08/26

DOI:10.1039/C5OB01634G

Low-molecular weight type I and II fucoidan derivatives with different sulfation patterns were designed and systematically synthesized from the corresponding common key intermediate and their anti-proliferative activities and apoptosis-inducing activities against human breast cancer (MCF-7) and human cervical epithelioid carcinoma (HeLa) cells were evaluated. Our results demonstrated that one of the type II fucoidan derivatives, 9, effectively reduced the number of viable MCF-7 and HeLa cells in a dose-dependent manner without causing cytotoxicity toward normal WI-38 cells, and that the anti-proliferative activity of 9 was comparable to that of fucoidan 2 isolated from Fucus vesiculosus. Moreover, it was found that both 2 and 9 exhibited similar apoptosis-inducing activities through activation of caspase-8 and -9 on MCF-7 and HeLa cells, respectively.

Photodegradation of amyloid β and reduction of its cytotoxicity to PC12 cells using porphyrin derivatives

Co-reporter:Ayumi Hirabayashi, Yutaka Shindo, Kotaro Oka, Daisuke Takahashi and Kazunobu Toshima

Chemical Communications 2014 - vol. 50(Issue 67) pp:NaN9546-9546

Publication Date(Web):2014/07/07

DOI:10.1039/C4CC03791J

A purpose-designed porphyrin–peptide hybrid effectively degraded amyloid β monomer and oligomers associated with Alzheimer's disease. Degradation was achieved using light irradiation in the absence of any additives and under neutral conditions. Moreover, the hybrid effectively neutralized the cytotoxicity of amyloid β in PC12 cells upon photoirradiation.

A solid-phase affinity labeling method for target-selective isolation and modification of proteins

Co-reporter:Daichi Kuwahara, Takahiro Hasumi, Hajime Kaneko, Madoka Unno, Daisuke Takahashi and Kazunobu Toshima

Chemical Communications 2014 - vol. 50(Issue 98) pp:NaN15604-15604

Publication Date(Web):2014/10/23

DOI:10.1039/C4CC06783E

Solid-phase affinity labeling of a target protein, peanut agglutinin (PNA), with the specifically designed chemical tool 1 selectively and effectively furnished the labeled PNA. Furthermore, this method was applicable to native human carbonic anhydrase II in red blood cell lysate using the chemical tool 2 without the need for tedious manipulations.

Photodegradation and inhibition of drug-resistant influenza virus neuraminidase using anthraquinone–sialic acid hybrids

Co-reporter:Yusuke Aoki, Shuho Tanimoto, Daisuke Takahashi and Kazunobu Toshima

Chemical Communications 2013 - vol. 49(Issue 12) pp:NaN1171-1171

Publication Date(Web):2012/12/18

DOI:10.1039/C2CC38742E

The anthraquinone–sialic acid hybrids designed effectively degraded not only non-drug-resistant neuraminidase but also drug-resistant neuraminidase, which is an important target of anti-influenza therapy. Degradation was achieved using long-wavelength UV radiation in the absence of any additives and under neutral conditions. Moreover, the hybrids efficiently inhibited neuraminidase activities upon photo-irradiation.

Chemical methods for degradation of target oligosaccharides using designed light-activatable organic molecules

Co-reporter:Daisuke Takahashi and Kazunobu Toshima

Chemical Communications 2012 - vol. 48(Issue 37) pp:NaN4407-4407

Publication Date(Web):2012/02/14

DOI:10.1039/C2CC17384K

Carbohydrates play crucial roles in a wide range of biological processes, including serious diseases. The development of novel and innovative methods for selective control of specific oligosaccharide functions has attracted much attention in the fields of chemistry, biology, and medicine. In this feature article, the development of novel chemical tools, which can degrade target oligosaccharides by irradiation with a specific wavelength of light under mild conditions without any additives, is introduced. This novel class of photochemical agents promise bright prospects for finding not only molecular-targeted bioprobes for understanding of the structure–activity relationships of oligosaccharides but also novel therapeutic drugs targeting oligosaccharides.

Photodegradation of lipopolysaccharides and the inhibition of macrophage activation by anthraquinone–boronic acid hybrids

Co-reporter:Daisuke Takahashi, Takuya Miura and Kazunobu Toshima

Chemical Communications 2012 - vol. 48(Issue 61) pp:NaN7597-7597

Publication Date(Web):2012/06/13

DOI:10.1039/C2CC33559J

Target-selective photodegradation of 3-deoxy-D-manno-2-octulopyranosonic acid (KDO) was achieved without additives and under neutral conditions using a designed anthraquinone–boronic acid hybrid and long wavelength UV light irradiation. The hybrid can photodegrade lipopolysaccharides (LPS) and inhibit macrophage activation induced by LPS.

Light-induced O-glycosylation of unprotected deoxythioglycosyl donors

Co-reporter:Mayuka Nakanishi, Daisuke Takahashi and Kazunobu Toshima

Organic & Biomolecular Chemistry 2013 - vol. 11(Issue 31) pp:NaN5082-5082

Publication Date(Web):2013/06/21

DOI:10.1039/C3OB41143E

The O-glycosylation of several unprotected deoxythioglycosides and alcohols using 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) under long-wavelength UV irradiation was effectively realized using a single electron transfer (SET) mechanism. In some cases, the use of p-methoxyboronic acid was very effective in temporary protection of the 1,3-diol (C4 and C6 positions) of the unprotected glycosyl donors to increase the yields of the obtained O-glycosides.

Target-selective photodegradation of oligosaccharides by a fullerene–boronic acid hybrid upon visible light irradiation

Co-reporter:Daisuke Takahashi, Shingo Hirono and Kazunobu Toshima

Chemical Communications 2011 - vol. 47(Issue 42) pp:NaN11714-11714

Publication Date(Web):2011/09/27

DOI:10.1039/C1CC15646B

A fullerene derivative was found to be capable of photodegrading oligosaccharides under irradiation with not only UV but also visible light. Furthermore, target-selective photodegradation of oligosaccharides (β-D-galactofuranosides) was achieved by a designed and synthesized fullerene–boronic acid hybrid upon irradiation with visible light in the absence of any additives under neutral conditions.

Systematic synthesis of sulfated oligofucosides and their effect on breast cancer MCF-7 cells

Co-reporter:Shinsuke Arafuka, Nozomi Koshiba, Daisuke Takahashi and Kazunobu Toshima

Chemical Communications 2014 - vol. 50(Issue 69) pp:NaN9834-9834

Publication Date(Web):2014/06/09

DOI:10.1039/C4CC03544E

Sulfated tetrafucosides 2–5 with different sulfation patterns, and a non-sulfated tetrafucoside 6, were designed and systematically synthesized from the common key intermediate 12. In addition, their anti-proliferative activities and apoptosis-inducing activities against human breast cancer MCF-7 cells were evaluated. Our results demonstrated that the sulfated tetrafucosides 2–4 reduced the number of MCF-7 cells in a dose-dependent manner, and of these, 3,4-O-sulfated type 4 showed the highest anti-proliferative activity, comparable to the activity of fucoidan 1 isolated from Fucus vesiculosus. Furthermore, it was revealed that both 1 and 4 exhibited apoptosis-inducing activities through activation of caspase-8 on MCF-7 cells.

Design, synthesis and evaluation of a boronic acid based artificial receptor for L-DOPA in aqueous media

Co-reporter:Haruna Ueno, Takayuki Iwata, Nozomi Koshiba, Daisuke Takahashi and Kazunobu Toshima

Chemical Communications 2013 - vol. 49(Issue 88) pp:NaN10405-10405

Publication Date(Web):2013/09/17

DOI:10.1039/C3CC45275A

Design and synthesis of a boronic acid based artificial receptor which selectively and effectively bound to a neurotransmitter, L-DOPA (1), in aqueous media. In addition, the synthetic receptor was found to effectively inhibit the DDC (L-DOPA decarboxylase) enzymatic reaction under physiological conditions.

Target-selective photo-degradation of AFP-L3 and selective photo-cytotoxicity against HuH-7 hepatocarcinoma cells using an anthraquinone–PhoSL hybrid

Co-reporter:Mai Okuyama, Haruna Ueno, Yuka Kobayashi, Hirokazu Kawagishi, Daisuke Takahashi and Kazunobu Toshima

Chemical Communications 2016 - vol. 52(Issue 10) pp:NaN2172-2172

Publication Date(Web):2015/12/14

DOI:10.1039/C5CC09542E

A purposefully-designed anthraquinone–Pholiota squarrosa lectin (PhoSL) hybrid effectively degraded α-fetoprotein-L3 (AFP-L3) associated with liver cancer. Degradation was achieved under light irradiation in the absence of any additives and under neutral pH conditions. Moreover, the hybrid effectively exhibited selective photo-cytotoxicity against HuH-7 hepatocarcinoma cells upon photo-irradiation.

Chemoselective glycosylations using 2,3-unsaturated-4-keto glycosyl donors

Co-reporter:Shunichi Kusumi, Sainan Wang, Tatsuya Watanabe, Kaname Sasaki, Daisuke Takahashi and Kazunobu Toshima

Organic & Biomolecular Chemistry 2010 - vol. 8(Issue 5) pp:NaN990-990

Publication Date(Web):2010/01/07

DOI:10.1039/B925587G

2,3-Unsaturated-4-keto glycosyl acetates were found to exhibit low reactivity under several glycosylation conditions. Chemoselective glycosylations were effectively performed using 2,3-unsaturated glycosyl and 2,3-dideoxy glycosyl acetates as armed glycosyl donors, and 2,3-unsaturated-4-keto glycosyl acetates as disarmed glycosyl donors.

Photo-induced glycosylation using reusable organophotoacids

Co-reporter:Ryosuke Iwata, Kanjiro Uda, Daisuke Takahashi and Kazunobu Toshima

Chemical Communications 2014 - vol. 50(Issue 73) pp:NaN10698-10698

Publication Date(Web):2014/07/24

DOI:10.1039/C4CC04753B

The glycosylation reactions of glycosyl trichloroacetimidates and several alcohols using an organophotoacid as an activator under photoirradiation proceeded smoothly to give the corresponding glycosides in high yields. The organophotoacid was recovered and reused without any loss of efficiency.

TOPICS

Abstract