Synthetic Study of Biologically Active Chiral Biaryls for Drug

药物用生物活性手性联芳基化合物的合成研究

• 批准号: 11554025
• 负责人: UEMURA Motokazu
• 金额: $ 8.96万
• 依托单位: Osaka Prefecture University, Faculty of Integrated Arts & Sciences
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11554025/
• 关键词: vancomycin; atropisomer; planar chiraliy; cross-coupling; 軸不斉ビアリール; アレーンクロム錯体; コルペンスアミン; アルカロイド; コンペンスアミン

Axially chiral biaryls are significantly important not only as chiral ligands or auxiliaries in asymmetric reactions but also for biologically active natural products. For the asymmetric synthesis of axially chiral biaryls, we have investigated the cross-coupling of the planar chiral arylhalide chromium tricarbonyl complexes with arylboronic acids. Thus, palladium (0)-mediated Suzuki-Miyaura cross-coupling of planar chiral (2, 6-disubstituted bromobenzene) chromium complexes with o-substituted arylboronic acids gave stereoselectively axially chiral mono Cr(CO)3-complexed biaryls. The axial stereochemistry of the cross-coupling products was found to be largely dependent on the steric bulkiness of ortho substituent of arylboronic acids and reaction conditions. The overall process gives a promising approach for the preparation of both atropisomers stereoselectively starting from a single planar chiral (arene)chromium complex. By utilizing these methodologies, biologically active axially chiral natural products, steganone, korupensamine and axially chiral A-B ring system of vancomycin were stereoselectively synthesized.

轴向手性联芳基不仅作为不对称反应中的手性配体或助剂，而且对于具有生物活性的天然产物也非常重要。为了不对称合成轴向手性联芳基化合物，我们研究了平面手性芳基卤化物三羰基铬配合物与芳基硼酸的交叉偶联。因此，平面手性（2, 6-二取代溴苯）铬配合物与邻位取代的芳基硼酸的钯（0）介导的Suzuki-Miyaura交叉偶联得到立体选择性轴向手性单Cr(CO)3配合的联芳基化合物。发现交叉偶联产物的轴向立体化学很大程度上取决于芳基硼酸邻位取代基的空间体积和反应条件。整个过程为从单一平面手性（芳烃）铬配合物开始立体选择性地制备两种阻转异构体提供了一种有前途的方法。利用这些方法，立体选择性合成了具有生物活性的轴向手性天然产物、丁酮、korupensamine和万古霉素轴向手性A-B环体系。

项目成果

Y.Tanaka, N. Taniguchi, M. Uemnura: "Asymmetric Synthesis of b-Amino Alcohols by Reductive Cross-Coupling of Benzylideneamine with Planar Chiral Benzaldehvdes"Org. Lett.. (in press).

Y.Tanaka、N. Taniguchi、M. Uemnura：“通过亚苄基胺与平面手性苯甲醛的还原交叉偶联合成 b-氨基醇”Org。

Kamikawa, K., Furusyo, M., Uno, T., Sato, Y., Konoo, A.,Bringmann,G.,Uemura,M: "Diastereoselective Ruthenium-Cp Complexation of Enantiopure Arene Compounds Possessing Stereogenic Benzvlic Alcohol Functionalities"Org. Lett.. 3. 3667-3670 (2001)

Kamikawa, K.、Furusyo, M.、Uno, T.、Sato, Y.、Konoo, A.、Bringmann,G.、Uemura,M：“具有立体苯并醇官能团的对映纯芳烃化合物的非对映选择性钌-Cp 络合”

Y.Tanaka, N.Taniguchi, M.Uemura: "Asymmetric Synthesis of β-Amino Alcohols by Reductive Cross-Coupling of Benzylideneamine with Planar Chiral Benzaldehydes"Org. Lett.. (in press).

Y.Tanaka、N.Taniguchi、M.Uemura：“通过苯亚甲基胺与平面手性苯甲醛的还原交叉偶联合成 β-氨基醇”Org。

N.,Taniguchi,T.Hata,M.Uemura: "Enantiomerically Pure Cyclic Trans 1,2-Diols,Diamines and Aminoalcohols by Intramolecular Pinacol Coupling of Planar Chiral (Arene) chromium Complexes"Angew.Chem.Int.Ed.Engl.. 38. 1232-1235 (1999)

N.，Taniguchi，T.Hata，M.Uemura：“通过平面手性（芳烃）铬络合物的分子内频哪醇偶联制备对映体纯环状反式 1,2-二醇、二胺和氨基醇”Angew.Chem.Int.Ed.Engl。

H.Koide,M.Uemura: "Axially Chiral Benzamides : Diastereoselective Nuceophilic Additions to Planar Chiral (N, N-Diethyl-2-Acyl-6Methylbenzamide) chromium Complexes"Tetrahedron Lett.. 40. 3443-3446 (1999)

H.Koide,M.Uemura：“轴向手性苯甲酰胺：平面手性（N,N-二乙基-2-酰基-6甲基苯甲酰胺）铬配合物的非对映选择性亲核加成”Tetrahedron Lett.. 40. 3443-3446 (1999)