Development of New Organic Reactions and Synthesis of Physiologically Active Substance

新型有机反应的发展与生理活性物质的合成

• 批准号: 62065005
• 负责人: NOYORI Ryoji
• 金额: $ 129.28万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Specially Promoted Research
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1990
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-62065005/
• 关键词: BINAL-H; TMSOTf; BINAP; BINAP-Rh; BINAP-Ru; MAD; CAB; Pd(0)Catalyzed deprotection; 有機亜鉛; アルキル化; 不斉クライゼン転位; アリル系保護基; 超純度DNA合成; 超原子価スズ化合物; 分子内エン反応; アミノアルコール; 有機亜鉛化合物; アシロキシボラン; 不斉DielsーAlder反応; BINAP錯体; プロスタグランジン合成; DNA固相合成; 不斉アルキル化

Research objectives : the following six objectives have been studied. (1) development of new synthetic organic reactions and management of the research (R. Noyori), (2) development of new reactions based on the use of typical elements (H. Yamamoto), (3) synthesis of oligonucleotides (B. Hayakawa), (4) prostaglandin synthesis (M. Suzuki), (5) synthesis of anthracyclin antibiotics (K. Maruoka), (6) synthesis of alkaloids, terpines, and vitamines (M. Kitamura).Results : successful results are summarized as follows. (1) organozinc aided stereoselective conjugate addition to enones and selective momoalkylation of enolates ; selective propargylation of carbonyls ; catalysis of PG endoperoxides ; asymmetric reduction of carbonyls with BINAL-H ; TMSOTf catalyzed aldol-type reactions ; practical synthesis of BINAP ; BINAP-Rh catalyzed asymmetric hydrogenation of olefins ; BINAP-Ru (II) catalyzed asymmetric hydrogenation of functionalized olefins ; kinetic resolution of allylic alcohols by BINAP … More -Ru catalyzed hydrogenation ; asymmetric synthesis of diols by double stereodifferentiation ; kinetic resolution of a racemic hydroxy ketones ; assymmetric synthesis using dynamic kinetic resolution ; asymmetric 1, 3-hydrogen shift catalyzed by BINAP-Rh catalyst ; kinetic resolution of 4-hydroxy-2-cyclopentenone ; catalytic enantioselective alkylation using organozinc reagents and elucidation of the mechanism ; efficient Pd(O)-catalyzed deprotection of allyl- and allyloxycarbonyl protective groups in nucleosides and ncleotides ; synthesis of unsymmetrically (2'-5'), (3'-5') linked oligonucleotides. (2) amphiphilic alkylation using alliminium agents, MAD and MAT : synthesis of steroids, conjugate addition of enones, selective reduction of two different ketones ; organoaluminium-promoted Claisen rearrangement : synthesis of Lardolure and Recifeolide ; CAB catalysis in organic synthesis : asymmetric Diels-Alder reaction, Aldol reaction, enereaction ; stereoselective synthesis of geranyl- and neryl-metal reagents ; synthesis of Ubiquinone 10. (3) synthesis of extremely pure 60 mers of oligonucleotides ; direct synthesis of solid-anchored DNA oligomers. (4) extremely shot-step synthesis of prostaglandin E_2 ; general syntheis of PGs ; synthesis of isocarbacyclin, synthesis of punaglandins ; synthesis of a photoaffinity probe reagent for prostacyclin receptor. (5) asymmetric Hetero-Diels-Alder reaction based on the use of binaphthol modified chiral alunminium agent AL ; efficient in situ generation of chiral Lewis acid ; asymmetric ene and Claisen reactions with AL ; stereoselcctive C-glycosidation ; synthesis of pseudosugars ; efficient synthesis of a partial structure of FK506 ; efficient construction of anthracyclin skeletons. (6) BINAP-Ru catalyzed enantioselective hydrogenation of enamides ; synthesis of a key intermediate for general synthesis of isoquinoline alkaloids ; asymmetric hydrogenation of allylic alcohols ; BINAP-Ru catalyzed asymmetric hydrogenation of bifunctionalized ketones ; asymmetric synthesis of 1beta-methylcarbapenems ; asymmetric synthesis of beta-amino acids ; asymmetric synthesis of camitine, statine, and analogues ; stereoselective synthesis of threonine type compounds. Less

研究目标：研究了以下六个目标。(1)新的有机合成反应的开发和研究的管理（R。Noyori），（2）开发基于典型元素的新反应（H。Yamamoto）;（3）寡核苷酸的合成（B. Hayakawa）;（4）前列腺素合成（M. Suzuki）;（5）蒽环类抗生素（K.（6）生物碱、萜类和维生素的合成（M.结果：成功的结果总结如下。(1)有机锌辅助的对烯酮的立体选择性共轭加成和烯醇化物的选择性单烷基化;羰基的选择性炔丙基化; PG内过氧化物的催化;用BINAL-H的羰基的不对称还原; TMSOTf催化的羟醛型反应; BINAP的实用合成; BINAP-Rh催化的烯烃的不对称氢化; BINAP-Ru（II）催化的官能化烯烃的不对称氢化; BINAP催化烯丙醇动力学拆分 ...更多信息 -Ru催化的氢化;二醇的双立体分化不对称合成;外消旋羟基酮的动力学拆分;动态动力学拆分的不对称合成; BINAP-Rh催化剂催化的不对称1，3-氢转移; 4-羟基-2-环戊烯酮的动力学拆分;有机锌试剂催化的对映选择性烷基化反应及其机理的阐明;核苷和核苷酸中烯丙基和烯丙氧基羰基保护基的有效Pd（O）催化脱保护;不对称（2 '-5'）、（3 '-5'）连接的寡核苷酸的合成。(2)两亲性烷基化：使用烯丙基试剂，MAD和MAT：合成类固醇，共轭加成的烯酮，两种不同的酮的选择性还原;有机铝促进的克莱森重排：合成Lardolure和Recifefelicide; CAB催化在有机合成：不对称Diels-Alder反应，Aldol反应，烯反应;立体选择性合成香叶基和橙花基金属试剂;合成泛醌10。(3)合成极纯的60聚体寡核苷酸;直接合成固体锚定的DNA寡聚体。(4)前列腺素E_2的快速合成;前列腺素的一般合成;异碳环素的合成; punaglandins的合成;前列环素受体光亲和探针试剂的合成。(5)基于使用联萘修饰的手性试剂AL的不对称Hetero-Diels-桤木反应;高效原位生成手性刘易斯酸;与AL的不对称烯和克莱森反应;立体选择性C-糖苷化;合成假糖;高效合成FK 506的部分结构;高效构建蒽环骨架。(6)BINAP-Ru催化的烯酰胺的对映选择性氢化;合成异喹啉生物碱的一般合成的关键中间体;烯丙醇的不对称氢化; BINAP-Ru催化的双官能化酮的不对称氢化; 1 β-甲基碳青霉烯的不对称合成; β-氨基酸的不对称合成; camitine，statine和类似物的不对称合成;苏氨酸型化合物的立体选择性合成。少

项目成果

K. Maruoka, T. Itoh, T. Shirasaka, and H. Yamamoto: "Asymmetric Hetero-Diels-Alder Reaction Catalyzed by Chiral Organoaluminum Reagent." J. Am. Chem. Soc.110. 310-312 (1988)

K. Maruoka、T. Itoh、T. Shirasaka 和 H. Yamamoto：“手性有机铝试剂催化的不对称杂狄尔斯-阿尔德反应”。

Y. Hayakawa, S. Wakabayashi, H. Kato, and R. Noyori: "The Allylic Protection Method in Solid-Phase Oligonucleotide Synthesis. An Efficient Preparation of Solid-Anchored DNA Oligomers." J. Am. Chem. Soc.112. 1691-1696 (1990)

Y. Hayakawa、S. Wakabayashi、H. Kato 和 R. Noyori：“固相寡核苷酸合成中的烯丙基保护方法。固体锚定 DNA 寡聚物的有效制备。”

M.Suzuki,Y.Morita,H.Koyaho,M.Koga,R.Noyori: "Threeーcomponent Coupling Synthesis of Prostag Candins.A Simplitied,General procedure" Tetrahedron. 46. 4809-4822 (1990)

M.Suzuki、Y.Morita、H.Koyaho、M.Koga、R.Noyori：“前列腺癌的三组分偶联合成。简化的一般程序”Tetrahedron 46。4809-4822（1990）

Y.Morita,M.Suzuki,R.Noyori: "An organozinc aid in alkylation and acylation of lithium eno lates" J.Org.Chem.54. 1785-1787 (1989)

Y.Morita、M.Suzuki、R.Noyori：“烯醇锂烷基化和酰化中的有机锌助剂”J.Org.Chem.54。

R.Noyori and M.Kitamura: "Modern Synthetic Methods" Springer Verlag, 83 (1989)

R.Noyori 和 M.Kitamura：“现代合成方法”Springer Verlag，83 (1989)