1996 Fiscal Year Annual Research Report

新規機能性薬物の分子設計と合成

Research Project

Project/Area Number	07457523
Research Institution	Teikyo University
Principal Investigator	池上四郎帝京大学, 薬学部, 教授 (10119555)
Co-Investigator(Kenkyū-buntansha)	東屋功帝京大学, 薬学部, 助手 (50276755) 高橋秀依帝京大学, 薬学部, 助手 (10266348) 大竹廣雄帝京大学, 薬学部, 助手 (50256054) 宮嵜洋二帝京大学, 薬学部, 助手 (70211597) 飯森隆昌帝京大学, 薬学部, 助教授 (90246025)
Keywords	Isocarbacyclin Analogue / Enediyne Compounds / Organolead Reagent / Ring Transformation / Decarboxylative Glycosidation / Glycosylene Orthoerste / Reductive Glycosidation / Cyclophellitol
Research Abstract	生体関連機能物質及び関連するリ-ド化合物に焦点を当て、分子設計と合成及び生物活性評価を通して構造活性相関を明らかにし、創薬の種を発見することにある。平成7〜8年度で得られた研究成果を以下に要約する。 1)有機鉛試薬を利用して確立したa-アルキニルケトンの汎用性ある合成法をイソカルバサイグリン類縁体のw-鎖に三重結合を導入した類縁体である13,14-ジデヒドロイソカルバサイクリンの合成を完成させた。この類縁体は興味ある生物活性を示した。 2)プロスタサイクリン受容体研究に新たな展開を意図して、アゴニスト活性の低い6-イソカルバサイクリンを光学活性体で合成した。残念なことに、イロプロスト受容体との結合能はイソカルバサイクリンに比して余り高くなかった。 3)循環器疾患治療薬の開発に対しては血液凝固の後期段階である腺溶系阻止因子としてトロンボモジュリンの生産増加を促す薬物の創製を目的として9-シスを環で固定したレチノイン酸類縁体を数種合成し、固定環が5員環の高活性新物質を発見した。 4)グリコシル化の新しい方法論を確立するための試みとして、ドナーとアクセプターをカルボナ-トとして連結するための合成法がほぼ確立できた。次は各種プロモタ-を用いて脱炭酸によるグリコシル化反応を選択性を含めて検討し、興味ある知見を得た。 5)新規グリコシル化反応開発の一環として、1-デヒドロ糖と他の糖の間で形成されるオルトエステルの合成と還元剤による還元的開裂によるグリコシル結合の形成を検討し、特徴的グリコシル化反応を見い出した。 6)合成中間体として汎用性の高い多置換シクロヘキサン環の構築を、Ferrier反応の遷移金属塩を用いる触媒的糖変換による実践的合成法として改良した。この変換がほぼ達成され、しかも、グルコースのみならずガラクトースやマンノースへも適用できることが判明した。

Research Products

(17 results)

All Other

All Publications (17 results)

[Publications] T.Iimori: "A Practical Preparation of Optically Active endo-Bicyclo [3.3.0] octan-2-ols" Chem.Pharm.Bull.45(1). 207-208 (1997)
[Publications] S.Hashimoto: "Site- and Enantiocontrol in Intramolecular C-H Insertion Reactions of α-Diazo Carbonyl Compounds Catalyzed by Dirhodium (II) Carboxylates." J.Synth.Org.Chem.Jpn.54(11). 988-999 (1996)
[Publications] S.Hashimoto: "A Regio- and Stereocontrolled Synthesis of 13,14-Didehydroisocarbacyclin" SYNLETT. NO.4. 324-326 (1996)
[Publications] T.Iimori: "A Novel Intramolecular Decarboxylative Glycosylation via Mixed Carbonate" Tetrahedron Lett.37(13). 2267-2270 (1996)
[Publications] T.Sasaki: "Regioselective Acetylation of 7-Deacetylforskolin with ^<11>C-Acetyl Chloride" J.Labelled Compds.and Radiopharmaceuticals. XXXVIII(4). 337-347 (1996)
[Publications] T.Iimori: "Palladium Chloride Mediated Rearrangement of 6-Deoxyhex-5-enopyranosides into Cyclohexanones" Tetrahedron Lett.37(5). 649-652 (1996)
[Publications] T.Iimori: "A Mild and Rapid Glycosylation Reaction Between Pyrimidine Bases and 2-Deoxyribofuranosyl N,N,N',N'-Tetramethylphosphroamidates" Heterocycles. 42(2). 485-488 (1996)
[Publications] N.Watanabe: "Dirhodium (II) Tetrakis [N-phthaloyl-(S)-tert-leucinate] : A Notable Catalyst for Enantiotopically Selective Aromatic Substitution Reactions of a-Diazocarbonyl Compounds" SYNLETT. 85-86 (1996)
[Publications] T.Sasaki: "1-Acetyl-7-deacetylforskolin : A Potential Non-Specific Inactive Analog of Forskolin for Estimation of its Specific High-Affinity Binding and Adenylyl Cyclase Stimulation in vitro" Life Science. 57. 1367-1373 (1995)
[Publications] S.Hashimoto: "An Attempt at the Direct Construction of 2-Deoxy-β-glycosidic Linkages Capitalizing on 2-Deoxyglycopyranosyl Diethyl Phosphites as Glycosyl Donora" SYNLETT. 1217-1273 (1995)
[Publications] S.Hashimoto: "An Extremely Mild and General Method for the Construction of 1,2-trans-β-Glycosidic Linkages via Glycopyranosyl Diethyl Phosphites with Participating Groups at C-2" Chem.Pharm.Bull.43(12). 2267-2269 (1995)
[Publications] S.Hashimoto: "A New Access to Mori's Intermediate for the Practiocal Synthesis of (-)-Periplanone-B" Chem.Lett.1091-1092 (1995)
[Publications] S.Hashimoto: "Highly Selective Glycosidation Reactions Capitalizing of Phosphorus-Containing Leaving Groups" J.Synth.Org.Chem.Japan. 53(7). 620-632 (1995)
[Publications] S.Hashimoto: "An Extremely Mild and Stereocontrolled Construction of 1,2-trans-β-Glycosidic Linkages Capitalizing of Benzyl-Protected Glycopyranosyl Diethyl Phosphites as Glycosyl Donors" Tetrahedron Lett.36(13). 2251-2254 (1995)
[Publications] N.Watanabe: "Asymmetric Creation of Quaternary Carbon Centers by Enantiotopically Selective Aromatic CH Insertion Catalyzed by Chiral Dirhodium (II) Carboxylates" Tetrahedron Lett.36(9). 1491-1494 (1995)
[Publications] 池上四郎、村上泰興編著: "有機化学" 朝倉書店, 1-6 (1996)
[Publications] 津田、二宮、金戸編著: "薬品化学改訂第6阪" 南江堂, 260-265 (1996)

1996 Fiscal Year Annual Research Report

新規機能性薬物の分子設計と合成

Principal Investigator

池上 四郎 帝京大学, 薬学部, 教授 (10119555)

Research Products

[Publications] T.Iimori: "A Practical Preparation of Optically Active endo-Bicyclo [3.3.0] octan-2-ols" Chem.Pharm.Bull.45(1). 207-208 (1997)

[Publications] S.Hashimoto: "Site- and Enantiocontrol in Intramolecular C-H Insertion Reactions of α-Diazo Carbonyl Compounds Catalyzed by Dirhodium (II) Carboxylates." J.Synth.Org.Chem.Jpn.54(11). 988-999 (1996)

[Publications] S.Hashimoto: "A Regio- and Stereocontrolled Synthesis of 13,14-Didehydroisocarbacyclin" SYNLETT. NO.4. 324-326 (1996)

[Publications] T.Iimori: "A Novel Intramolecular Decarboxylative Glycosylation via Mixed Carbonate" Tetrahedron Lett.37(13). 2267-2270 (1996)

[Publications] T.Sasaki: "Regioselective Acetylation of 7-Deacetylforskolin with ^<11>C-Acetyl Chloride" J.Labelled Compds.and Radiopharmaceuticals. XXXVIII(4). 337-347 (1996)

[Publications] T.Iimori: "Palladium Chloride Mediated Rearrangement of 6-Deoxyhex-5-enopyranosides into Cyclohexanones" Tetrahedron Lett.37(5). 649-652 (1996)

[Publications] T.Iimori: "A Mild and Rapid Glycosylation Reaction Between Pyrimidine Bases and 2-Deoxyribofuranosyl N,N,N',N'-Tetramethylphosphroamidates" Heterocycles. 42(2). 485-488 (1996)

[Publications] N.Watanabe: "Dirhodium (II) Tetrakis [N-phthaloyl-(S)-tert-leucinate] : A Notable Catalyst for Enantiotopically Selective Aromatic Substitution Reactions of a-Diazocarbonyl Compounds" SYNLETT. 85-86 (1996)

[Publications] T.Sasaki: "1-Acetyl-7-deacetylforskolin : A Potential Non-Specific Inactive Analog of Forskolin for Estimation of its Specific High-Affinity Binding and Adenylyl Cyclase Stimulation in vitro" Life Science. 57. 1367-1373 (1995)

[Publications] S.Hashimoto: "An Attempt at the Direct Construction of 2-Deoxy-β-glycosidic Linkages Capitalizing on 2-Deoxyglycopyranosyl Diethyl Phosphites as Glycosyl Donora" SYNLETT. 1217-1273 (1995)

[Publications] S.Hashimoto: "An Extremely Mild and General Method for the Construction of 1,2-trans-β-Glycosidic Linkages via Glycopyranosyl Diethyl Phosphites with Participating Groups at C-2" Chem.Pharm.Bull.43(12). 2267-2269 (1995)

[Publications] S.Hashimoto: "A New Access to Mori's Intermediate for the Practiocal Synthesis of (-)-Periplanone-B" Chem.Lett.1091-1092 (1995)

[Publications] S.Hashimoto: "Highly Selective Glycosidation Reactions Capitalizing of Phosphorus-Containing Leaving Groups" J.Synth.Org.Chem.Japan. 53(7). 620-632 (1995)

[Publications] S.Hashimoto: "An Extremely Mild and Stereocontrolled Construction of 1,2-trans-β-Glycosidic Linkages Capitalizing of Benzyl-Protected Glycopyranosyl Diethyl Phosphites as Glycosyl Donors" Tetrahedron Lett.36(13). 2251-2254 (1995)

[Publications] N.Watanabe: "Asymmetric Creation of Quaternary Carbon Centers by Enantiotopically Selective Aromatic CH Insertion Catalyzed by Chiral Dirhodium (II) Carboxylates" Tetrahedron Lett.36(9). 1491-1494 (1995)

[Publications] 池上四郎、村上泰興編著: "有機化学" 朝倉書店, 1-6 (1996)

[Publications] 津田、二宮、金戸編著: "薬品化学 改訂第6阪" 南江堂, 260-265 (1996)

池上四郎帝京大学, 薬学部, 教授 (10119555)

[Publications] 津田、二宮、金戸編著: "薬品化学改訂第6阪" 南江堂, 260-265 (1996)