Development of New Organic Reactions and Synthesis of Physiologically Active Substance

研究目标：研究了以下六个目标。(1)开发新的合成有机反应和研究管理（R. Noyori），(2)开发基于典型元素的新反应（H. Yamamoto），(3)合成寡核苷酸（B. Hayakawa），(4)合成前列腺素（M. Suzuki），(5)合成蒽环类抗生素（K. Maruoka），(6)合成生物碱，萜松和维生素（M. Kitamura）。结果：成功的结果总结如下。(1)有机锌辅助烯酮立体选择性共轭加成和烯醇酯选择性单烷基化；羰基选择性丙基化；PG内过氧化物催化作用；羰基与BINAL-H的不对称还原反应TMSOTf催化醛型反应；BINAP的实用合成；BINAP-Rh催化烯烃不对称加氢反应BINAP-Ru （II）催化功能化烯烃的不对称加氢反应多钌催化氢化反应对烯丙醇的动力学拆分双立体分化法合成二醇的不对称反应外消旋羟基酮的动力学拆分动态动力学分辨非对称合成；BINAP-Rh催化剂催化的不对称1,3氢位移；4-羟基-2-环戊酮的动力学拆分有机锌试剂催化对映选择性烷基化反应及其机理的研究Pd(O)催化核苷和核苷酸中烯丙基和烯丙氧羰基保护基的高效脱保护；不对称（2’-5’），（3’-5’）连接寡核苷酸的合成。(2)用铝剂MAD和MAT进行两亲性烷基化：合成甾体、烯酮的共轭加成、两种不同酮的选择性还原；有机铝促进Claisen重排：Lardolure和Recifeolide的合成有机合成中的CAB催化：不对称Diels-Alder反应、Aldol反应、能量反应；香叶基和奈基金属试剂的立体选择性合成合成泛醌10。(3)极纯60米寡核苷酸的合成；直接合成固体锚定DNA低聚物。(4)前列腺素E_2的极短合成；PGs的一般合成；异碳环素的合成、普纳格兰丁素的合成前列环素受体光亲和探针试剂的合成。(5)基于联萘酚改性手性铝剂AL的不对称Hetero-Diels-Alder反应；手性路易斯酸的原位高效生成；不对称烯与AL的Claisen反应；立体选择性c -糖苷化；假糖的合成；FK506部分结构的高效合成高效构建蒽环类药物骨架。(6) BINAP-Ru催化酰胺对映选择性加氢反应；异喹啉类生物碱合成关键中间体的合成烯丙醇的不对称加氢反应BINAP-Ru催化双功能化酮的不对称加氢反应1 -甲基碳青霉烯类的不对称合成氨基酸的不对称合成；camitine、他汀及其类似物的不对称合成立体选择性合成苏氨酸类化合物。少

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