Synthesis of Bioactive Anthraquinones Using Intramolecular

分子内合成生物活性蒽醌类化合物

• 批准号: 12640521
• 负责人: UNO Hidemitsu
• 金额: $ 2.18万
• 依托单位: Ehime University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12640521/
• 关键词: Espicufolin; K1115A; Intramolecular Michael addition; Intramolecular condensation; Anthraquinones; AH-1763 IIa; Intramolecular acyl migration; SS43405E; 分子内アシル転移反応; ピラノアントラキノン; アシルナフトキノン

Recently, compounds with an anthraquinone skeleton have been reported to have many interesting activities such as neuronal cell-protecting activity (espicufolin), anti-helpetic activity (AH-1763 IIa), and carbon clearance activity (SS43405E). We planned not only to prepare the bioactive anthraquinones and their analogs, but also to create highly active compounds by elucidation of their in vivo action mechanisms on neuronal cells.In this research, we achieved the synthesis and absolute structure determination of espicufolin, the synthesis and absolute structure determination of SS43405E, and establishment of the synthetic routes to dihydroxyanthraquinones represented by K1115A. Racemic and S-espicfolins were subject to bioassay by using mouse embryonic neuronal cells. The espicufolins showed no protecting activity for the toxicity of glutamate but weak cytotoxiciry to the cells employed. In the synthetic approach for antihelpetic AH-1763 IIa, two different routes were examined, but total synthesis has not been achieved, yet. We now intended to prepare the side chain of AH-1763 IIa by asymmetric aldol condensation.

最近，已经报道了具有蒽醌骨架的化合物具有许多令人感兴趣的活性，例如神经元细胞保护活性（espicufolin）、抗疱疹活性（AH-1763 IIa）和碳清除活性（SS 43405 E）。本研究完成了刺果苦皮素（espicufolin）的合成及结构测定、SS 43405 E的合成及结构测定，以及以K1115 A为代表的二羟基蒽醌类化合物的合成路线的建立。外消旋和S-刺叶素通过使用小鼠胚胎神经元细胞进行生物测定。对谷氨酸的毒性无保护作用，但对细胞毒性较弱。在抗疱疹药AH-1763 IIa的合成方法中，检查了两种不同的路线，但尚未实现全合成。我们现在打算通过不对称羟醛缩合来制备AH-1763 IIa的侧链。

项目成果

H.Uno, Y.Nagamachi, E.Honda, A.Masumoto, and N.Ono: "Regioselective Preparation of 1,6- and 1,8-Dihydroxy-9,10-anthraquinones from the Common Intermediates : Synthesis of Aloesaponarin and K1115A"Chem.Lett.. 1014-1015 (2000)

H.Uno、Y.Nagamachi、E.Honda、A.Masumoto 和 N.Ono：“从常见中间体中区域选择性制备 1,6- 和 1,8-二羟基-9,10-蒽醌：芦荟皂苷和

H.Uno et al.: "Synthesis of Espicufolin Based on 6-Endo Ring Closure of o-Alkynoylnaphthols"J. Chem. Soc., Perkin Trans. 1. 229-238 (2001)

H.Uno等：“基于邻炔酰萘酚6-Endo环闭合的Espicufolin的合成”J。

H.Uno et al.: "Regioselective Preparation of 1,6-and 1,8-Dihydroxy-9,10-anthraquinones from the Common Intermediates : Synthesis of Aloesaponarin and K1115A"Chem.Lett.. 1014-1015 (2000)

H.Uno 等人：“从常见中间体中区域选择性制备 1,6-和 1,8-二羟基-9,10-蒽醌：芦荟皂苷和 K1115A 的合成”Chem.Lett.. 1014-1015 (2000)

K.Sakamoto et al.: "A Novel Synthetic Approach to Benzo[h]chromones via Sequential Intramolecular Alkynoyl Transfer Followed by 6-endo Ring Closure"Tetrahedron Lett.. 41. 1819-1823 (2000)

K.Sakamoto 等人：“通过顺序分子内炔酰基转移随后进行 6-endo 环闭合来合成苯并[h]色酮的新颖方法”Tetrahedron Lett.. 41. 1819-1823 (2000)

K.Sakamoto et al.: "A Novel Synthetic Approach to Benzo [h] chromones via Sequential Intramolecular Alkynoyl Transfer Follower by 6-endo Ring Closure"Tetrahedron Lett.. 41. 1819-1823 (2000)

K.Sakamoto 等人：“通过 6-endo 环闭合的顺序分子内炔酰基转移跟随器合成苯并 [h] 色酮的新颖方法”Tetrahedron Lett.. 41. 1819-1823 (2000)