Design of Versatile Chiral Building Blocks via Asymmetric Cleavage of the Bridged Bicyclic Ketone and Its Applications to the Natural Product Synthesis

通过桥联双环酮的不对称裂解设计多功能手性结构单元及其在天然产物合成中的应用

• 批准号: 03670994
• 负责人: MOMOSE Takefumi
• 金额: $ 1.15万
• 依托单位: TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670994/
• 关键词: bridged bicyclic compound; 'fork head' ketone; (+)-monomorine I; (-)-indolizidine 223AB; sigma-symmetric ring-crossed glycol; functionalized 3-piperidinol; (+)-monomorineI; (-)-indolizidine 223AB; σ対称型双環系ジオール; α,α'位シス置換3ーピペリジノール; “fork head"位ケトン

We have focused our attention on the bridged bicyclic compound as one of the useful starting material for stereoselective synthesis of natural products because of its conformational rigidity and sigma-symmetry.Thus, in this research project, we have developed the asymmetric synthesis of versatile chiral building blocks for the synthesis of biologically active alkaloids based on the asymmetric cleavage of the nitrogen-bridged bicyclic 'fork head' ketone according to the Koga's protocol to afford cis-2,5-disubstituted pyrrolidine, cis-2,6-disubstituted, and cis-3,5- disubstituted piperidine ring systems.As a result, we acheived the total synthesis of (+)-dihydropinidine, the dihydro compound of (-)-pinidine, (+)-monomorine I, a trail pheromone of the pharaoh ant, and (-)-indolizidine 223AB.In addition, we designed a sigma-symmetric ring-crossed glycol and examined its transformation into a homochiral ketone via lipase-catalyzed differentiation of the hydroxyl. The cleavage of the ketone obtained furnished a highly functionalized 3-piperidinol.

由于桥连双环化合物的构象刚性和σ对称性，我们将注意力集中在它作为天然产物立体选择性合成的有用起始原料之一上。我们已经开发了用于合成生物活性生物碱的多功能手性结构单元的不对称合成，按照古贺等人的方法，以桥连双环“叉头”酮为起始原料，合成了顺式-2，5-二取代吡咯烷、顺式-2，6-二取代和顺式-3，5-二取代哌啶环系，从而实现了（-）-二氢哌啶的二氢化合物（+）-二氢哌啶的全合成，此外，我们还设计了一个σ对称的环交叉二醇，并考察了其通过脂肪酶催化羟基的分化转化为纯手性酮。所得酮的裂解提供高度官能化的3-哌啶醇。

项目成果

T.Momose,N.Toyooka and M.Jin: "Asymmetric Twin-Ring Differentiation by Lipase-Catalyzed Enantiotoposelective Reaction of the Ring-Crossed meso Glycol:Asymmetrie Synthesis of a Highly Frnctionalized Piperidine from the Coujeined Twin Piperidine System" Tet

T.Momose、N.Toyooka 和 M.Jin：“脂肪酶催化环交叉内消旋乙二醇的对映选择性反应进行不对称双环分化：从 Coujeined 双哌啶系统不对称合成高度官能化哌啶”Tet

T.Momose,H.Inoue,N.Toyooka,O.Muraoka,and K.Okumura: "3ーAzabicyclo[3.3.1]nonaneー7,9ーdione 9ーHydrate:An Extraordinarily Stable Hydrate of the Cyclic Ketone Bearing No Vicinal Electrouーwithdrawing Functionality." Heterocycles,.

T.Momose、H.Inoue、N.Toyooka、O.Muraoka 和 K.Okumura：“3－氮杂双环[3.3.1]壬烷－7,9－二酮 9－水合物：环酮轴承的极其稳定的水合物无邻位电子撤回功能。”杂环，。

T.Momose,N.Toyooka and Y.Hirai: "Asymmetric Cleavage of 9-Azabicyclo[3.3.1]nonan-3-one into cis-2,6-Disubsitituted Piperidine.A Facile Approach to a Chiral Building Black for Alkaloid Synthesis" Chemistry Letters. 1319-1322 (1990)

T.Momose、N.Toyooka 和 Y.Hirai：“9-氮杂双环[3.3.1]壬南-3-酮不对称裂解为顺式-2,6-二取代哌啶。用于生物碱合成的手性建筑黑的简便方法

T.Momose,M.Toshima,N.Toyoka,and Y.Hirai: "Bicyclo[3.3.1]nonanes as Synthetic Intermediates.XVIII.Asymmetric Cleavage of wーAzabicyelo[3.n.1]alkanー3ーones at the “fork head"Ketone." Chem.Pharm.Bull.,.

T.Momose、M.Toshima、N.Toyoka 和 Y.Hirai：“双环[3.3.1]壬烷作为合成中间体。XVIII.wーAzabicyelo[3.n.1]alkanー3ーones 的不对称裂解“叉头”酮。

T.Momose,M.Toshima,N.Toyooka,and Y.Hirai: "Bicyclo[3.3.1]nonanes as synthetie Intermediates.XXI.Asymmetrie Synthesis and Absolute Stereochemistry of the Ant Venom Alkaloid 3,5ーDi(5ーhexenyl)pyrrobzidine." Chem.Pharm.Bull.,.

T.Momose、M.Toshima、N.Toyooka 和 Y.Hirai：“双环[3.3.1]壬烷作为合成中间体。XXI.蚂蚁毒生物碱 3,5-Di(5-己烯基)的不对称合成和绝对立体化学）吡咯西啶。”Chem.Pharm.Bull.,.