Development of the effecient synthetic methods of some pharmeceuticals by using the generalized asymmetric epoxidation

利用广义不对称环氧化开发一些药物的有效合成方法

• 批准号: 06558093
• 负责人: KATSUKI Tsutomu
• 金额: $ 4.16万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06558093/
• 关键词: asymmetric epoxidation; aziridination; (salen) manganese complex; benzylic hydroxylation; asymmetric oxidation; 不斉酸化; エポキシド; 昆虫フェロモン; メタラオキセタン中間体

We have studied on asymmetric epoxidation of simple olefins to provide a useful methodology for the synthesis of pharmaceuticals and found that well-designed (salen) manganese (III) complexes are efficient catalysts for epoxidation of conjugated olefins. To develop the more effective catalyst, we examined about the reaction mechanism of epoxidation using a (salen) manganese (III) catalyst this year and could propose a unique mechanism of asymmetric induction by the catalysts : the high asymmetric induction by salen catalyst is mainly attributable to asymmetric non-planar structure of the salen ligand. Based on this new knowledge, we could find that an achiral (salen) manganese (III) complex catalyzes epoxidation in the presence of an optically amine in a enantioselective manner. Although enantioselectivity of the reaction is not high enough for practical use at present, this new methodology using readily available and non-expensive achiral salen catalyst will lead to the development of more economical epoxidation.We also developed asymmetric aziridination of styrane derivatives and asymmetric benzylic hydroxylation by the modification of the (salen) manganese (III) complex we had reported.These new reactions are expected to be efficient tools for the synthesis of wide variety of pharmaceuticals.

我们已经研究了简单烯烃的不对称环氧化，为合成药物提供了有用的方法，发现精心设计的（盐）锰（III）配合物是有效的催化剂，可用于缀合的烯烃。为了开发更有效的催化剂，我们使用（Salen）锰（III）催化剂研究了环氧化的反应机理，今年可能提出了催化剂的不对称诱导的独特机制：Salen Catalyst的高不对称诱导诱导主要可归因于salenar ligand salen ligand的非对称性非平稳结构。基于这些新知识，我们可以发现，在光学胺的存在下以映选择性方式在存在光学胺的情况下催化环氧化。尽管反应的对抗序列性目前不足以实用，但这种新方法使用易于使用和非贵族盐催化剂将导致更经济的环氧化的发展。我们还通过对苯二元式（Salengan istrification of Salense istrification of Salense istrification of Salense istrification of Salense istrification of Salense istrification of Salense inii inii inii inii inii inii inii inii ishense ishense）（Salen）（salense）（salense）（Salen）（Salen）（Salen）（salenne）。预计将是合成各种药物的有效工具。

项目成果

北島浩: "N,N,N',N'-Tetraalkyl-2,2'-dihydroxy-1,1'-binaphthyl-3,3'-dicarboxamides : Novel Chiral Auxiliaries for Asymmetric Simmons-Smith Cyclopropanation of Allylic" Bull.Chem.Soc.Jpn.70・1. 207-217 (1997)

Hiroshi Kitajima：“N,N,N,N-四烷基-2,2-二羟基-1,1-联萘基-3,3-二甲酰胺：用于烯丙基不对称 Simmons-Smith 环丙烷化的新型手性助剂”公牛.Chem.Soc.Jpn.70・1. 207-217 (1997)

濱田哲也: "Mechanism of One Oxygen Atom transfer from Oxo (salen) manganese (V) Complex to Olefins." Tetrahedron. 52・2. 515-530 (1996)

Tetsuya Hamada：“一个氧原子从 Oxo (salen) 锰 (V) 络合物转移到四面体的机理”52・2（1996）。

T.Hashihayata, Y.Ito, and T.Katsuki: "Enantioselective Epoxidation of 2,2-Dimethylchromenes Using Achiral Mn-Salen Complex as a Catalyst in the Presence of Chiral Amine." Synlett.1079-1081 (1996)

T.Hashihayata、Y.Ito 和 T.Katsuki：“在手性胺存在下，使用非手性 Mn-Salen 络合物作为催化剂对 2,2-二甲基色烯进行对映选择性环氧化。”

三瓶 大輔: "Mn-Salen Catalyzed Asymmeric Epoxidation of 1,3-Cycloalkadienes and Dialkylsubstituted Z-olefins" Synlett. 827-828 (1995)

Daisuke Sanpei：“Mn-Salen 催化的 1,3-环二烯和二烷基取代的 Z-烯烃的不对称环氧化”Synlett 827-828 (1995)。

Y.Noguchi, R.Irie, T.Fukuda, and T.Katsuki: "Mn-Salen Catalyzed Asymmetric Epoxidation of ((]SY.+-。[))-3-Alkylindene : Reagent-Dependent Stereoselectivity." Tetrahedron Lett.37. 4533-4536 (1996)

Y.Noguchi、R​​.Irie、T.Fukuda 和 T.Katsuki：“Mn-Salen 催化的 ((]SY.+-.[))-3-Alkylindene 的不对称环氧化：试剂依赖性四面体 Lett。” 37. 4533-4536 (1996)