1991 Fiscal Year Annual Research Report

特異な構造をもつヌクレオシドの化学合成と反応

Research Project

Project/Area Number	03242103
Research Institution	Tohoku University
Principal Investigator	金子主税東北大学, 薬学部, 教授 (40013833)
Co-Investigator(Kenkyū-buntansha)	佐々木琢磨金沢大学, がん研究所, 教授 (90109976) 関根光雄東京工業大学, 生命理工学部, 助教授 (40111679) 小林進東京大学, 薬学部, 助教授 (70101102) 向山光昭東京理科大学, 理学部, 教授 (60016003)
Keywords	レトロアルド-ル反応 / 炭素環ヌクレオシド / 抗HIV活性 / グリコシル化反応 / ブレオマイシン / ディスタマイシン / 分岐RNA / 抗腫瘍性
Research Abstract	DielsーAlder反応の新しいジエノフィルとして,ビニルホスホネ-トを開発し,シクロペンタジエンとのDielsーAlder付加体より還元条件下でのレトロアルド-ル反応を用いて炭素環Cーヌクレオシド前駆体の合成を達成した。また、ビシクロアシドの水素化ホウ素ナトリウムによる還元的アシド結合開裂反応を行い炭素環ヌクレオシドの一般合成法の開発に成功した。本手法を用いて各種新規炭素環ヌクレオシドを合成し,それらの中に顕著な抗HIV活性を有するBCAを見出した(金子)。グリコシル化反応に関して,ルイス酸の組合せ,あるいはルイス酸と銀塩の組合せにより生じるカチオン活性種が1ー0ーアセチル糖の活性化に有効であり,トリメチルシリルエ-テルをグリコシル化ドナ-とする触媒的0ーグリコシル化反応の開発に成功した。また,1ーヒドロキシ糖の活性化剤として,トリフェニルホスフィンオキシドと無水トリフラ-トの組合せが有効であることも明らかにした(向山)。ブレオマイシンの金属部位モデルにディスタマイシンを連結した化合物によりDNAのアデニン,チミンに富む部分を切断することが出来た(小林)。2'および3'に保護された2つのリン酸基をもつ合成ユニットを用いて分岐RNAの合成研究を行い,2'リン酸基が転移しないため立体障害をもつリン酸基のヌクレオシドの糖水酸基への導入反応を確立した。また核酸合成条件下におけるこれら立体障害をもつリン酸基の保護基の基本的な諸性質を明らかにすることができた。さらに,3',5'環状シリルエ-テル型の保護基の選択的脱保護には弱酸性条件下おこなうと、極めて選択的にリン酸基の転移は防げるという基礎的かつ重要な結果を得た(関根)。新規ヌクレオシド,DMDC,CNDAはマウス実験腫瘍ばかりでなく、ヒト固型腫瘍に対しても強い抗腫瘍性を示すことを見出した(佐々木)。

Research Products
(12 results)

All Other

All Publications (12 results)

[Publications] Chikara Kaneko: "A new method for the stereoselective synthesis of nucleosides by means of sodium borohydride mediated C-C or C-N bond cleavage reaction" Israel J.Chem.,.
[Publications] Nobuya Katagiri: "Synthesis of nucleosides and related compounds.20.Synthesis of carbocyclic nucleosides from 2-azabicyclo 2.2.1 heptan-3-ones:sodium borohydride mediated carbon-nitrogen bond cleage of five- and six-membered lactams" Chem.Pharm.Bull.39. 1112-1122 (1991)
[Publications] Nobuya Katagiri: "Synthesis of purine bases having a di(hydroxymethyl)cyclopentenyl group by means of high-pressure reaction and their anti-HIV activity" Nucleic Acids Research,Symposium Ser.24. 5-6 (1991)
[Publications] Nobuya Katagiri: "Synthesis and anti-HIV activity of 9-(c-4,t-5-bishydroxy-methylcyclopent-2-en-r-l-yl)-9H-adenine" J.Med.Chem.,.
[Publications] Nobuya Katagiri: "Chiral 2-vinyl-1,3,2-oxazaphospholidin-2-ones:new dienophiles for asymmetric Diels-Alder reactions" J.Chem.Soc.,Chem.Commun.1429-1430 (1991)
[Publications] Teruaki Mukaiyama: "The evaluation of catalysts generated from Lewis acids and silver perchlorate in a highly selective glycosilation of 1-0-acetyl-D-glucose" Chemistry Lett.985-988 (1991)
[Publications] Teruaki Mukaiyama: "A highly stereosective synthesis of -glucosides from 1-0-acetyl glucose by use of Tin(IV) chloride-silver perchlorate catalyst system" Chemistry Lett.533-536 (1991)
[Publications] Masahisa Nakada: "A novel synthesis of asylsilanes" Tetrahedron Lett.32. 4929-4932 (1991)
[Publications] Mitsuo Sekine: "A convenient method for the synthesis of N2,N2-dimethylguanosine by reductive C-S bond cleavage with tributyltin hydride" J.Org.Chem.56. 1224-1227 (1991)
[Publications] Mitsuo Sekine: "A convenient method for removal of the t-butyl group from nucleoside bis(t-butyl)phosphates under non-acidic conditions" Tetrahedron Lett.32. 395-398 (1991)
[Publications] Akira Matsuda: "2'-C-Cyano-2'-deoxy-1- -D-arabinofuranosylcytidine(CNDA C):Design of a potential mechanism-based DNA-strand-breaking antineoplastic nucleosides" J.Med.Chem.34. 2917-2919 (1991)
[Publications] Akira Matsuda: "Synthesis of a new broad spectrum of antineoplastic nucleosides,2'-deoxy-2'-methylidenecytidine" J.Med.Chem.34. 812-819 (1991)

1991 Fiscal Year Annual Research Report

特異な構造をもつヌクレオシドの化学合成と反応

Principal Investigator

金子 主税 東北大学, 薬学部, 教授 (40013833)

Research Products

[Publications] Chikara Kaneko: "A new method for the stereoselective synthesis of nucleosides by means of sodium borohydride mediated C-C or C-N bond cleavage reaction" Israel J.Chem.,.

[Publications] Nobuya Katagiri: "Synthesis of nucleosides and related compounds.20.Synthesis of carbocyclic nucleosides from 2-azabicyclo 2.2.1 heptan-3-ones:sodium borohydride mediated carbon-nitrogen bond cleage of five- and six-membered lactams" Chem.Pharm.Bull.39. 1112-1122 (1991)

[Publications] Nobuya Katagiri: "Synthesis of purine bases having a di(hydroxymethyl)cyclopentenyl group by means of high-pressure reaction and their anti-HIV activity" Nucleic Acids Research,Symposium Ser.24. 5-6 (1991)

[Publications] Nobuya Katagiri: "Synthesis and anti-HIV activity of 9-(c-4,t-5-bishydroxy-methylcyclopent-2-en-r-l-yl)-9H-adenine" J.Med.Chem.,.

[Publications] Nobuya Katagiri: "Chiral 2-vinyl-1,3,2-oxazaphospholidin-2-ones:new dienophiles for asymmetric Diels-Alder reactions" J.Chem.Soc.,Chem.Commun.1429-1430 (1991)

[Publications] Teruaki Mukaiyama: "The evaluation of catalysts generated from Lewis acids and silver perchlorate in a highly selective glycosilation of 1-0-acetyl-D-glucose" Chemistry Lett.985-988 (1991)

[Publications] Teruaki Mukaiyama: "A highly stereosective synthesis of -glucosides from 1-0-acetyl glucose by use of Tin(IV) chloride-silver perchlorate catalyst system" Chemistry Lett.533-536 (1991)

[Publications] Masahisa Nakada: "A novel synthesis of asylsilanes" Tetrahedron Lett.32. 4929-4932 (1991)

[Publications] Mitsuo Sekine: "A convenient method for the synthesis of N2,N2-dimethylguanosine by reductive C-S bond cleavage with tributyltin hydride" J.Org.Chem.56. 1224-1227 (1991)

[Publications] Mitsuo Sekine: "A convenient method for removal of the t-butyl group from nucleoside bis(t-butyl)phosphates under non-acidic conditions" Tetrahedron Lett.32. 395-398 (1991)

[Publications] Akira Matsuda: "2'-C-Cyano-2'-deoxy-1- -D-arabinofuranosylcytidine(CNDA C):Design of a potential mechanism-based DNA-strand-breaking antineoplastic nucleosides" J.Med.Chem.34. 2917-2919 (1991)

[Publications] Akira Matsuda: "Synthesis of a new broad spectrum of antineoplastic nucleosides,2'-deoxy-2'-methylidenecytidine" J.Med.Chem.34. 812-819 (1991)

金子主税東北大学, 薬学部, 教授 (40013833)