Studies toward Determination of Absolute Stereochemistry and Total Synthesis of Stereochemically Undefined Bioactive Natural Polyether Macrolides

绝对立体化学测定及立体化学未定义生物活性天然聚醚大环内酯的全合成研究

基本信息

批准号：
16510152
负责人：
FUJIWARA Kenshu
金额：
$ 2.56万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

Toward development of an efficient methodology for determination of the absolute stereochemistry of undefined bioactive natural polyether macrolides, goniodomin A and caribenolide I were investigated in view of organic synthetic chemistry. Goniodomin A was isolated from dinoflagellate Alexandrium hiranoi as an antifungal agent by Murakami in 1988. Later, its particular bioactivities, such as modulation of actomyosin ATPase activities, increasing the filamentous actin content of human astronoma cells, and antiangiogenic activity via inhibition of actin reorganization in endothelial cells, were found. Although its detailed NMR data and unique planer structure featured by a 32-membered macrolactone including 5- and 6-membered cyclic ethers (the A-,D- and E-ring parts), a spirocyclic acetal (the BC-ring part), and a 6-membered cyclic hemiacetal (the F-ring part) were reported, the stereochemistry of goniodomin A was unclear. Caribenolide I was isolated from dinoflagellate Amphidinium sp.S1 … More -36-5 as a cytotoxic agent, which showed strong cytotoxicity against HCT116 with 1.6 nM of IC_<50>, by Shimizu in 1995. While its planer structure, characterized by a 26-membered macrolactone with an oxolane, a 6-membered cyclic hemiacetal, an epoxide, and 5 hydroxy groups (including a hemiacetal hydroxy group), was elucidated, its relative and absolute configurations were not determined. From this research project, determination of partial stereochemistry and partial synthesis of goniodomin A have been achieved as follows : (1)the relative configurations of the A-,BC-,D-,E-, and F-ring parts were predicted from the NMR data of goniodomin A reported by Murakami ; (2)the A-,D-,E-, and F-ring segments possessing the predicted stereochemistries were synthesized ; (3)NMR data of natural goniodomin A agreed well with those of synthetic A-,D-,E-, and F-ring segments ; (4)relative stereochemistry of the DE-ring part was determined by comparison of NMR data of natural goniodomin A with the synthetic DE-ring included in a macro ring ; (5)the proper stereochemistry of the BC-ring part was elucidated by synthetic assessment of the predicted structure from the NMR data of goniodomin A. Some synthetic analogues of caribenolide I were also designed in order to determine its relative stereochemistry. Less

鉴于有机合成化学，研究了有效的生物活性天然聚醚大环内酯类，Goniodomin A和Caribenolide I的有效方法来开发有效的方法论。 Goniodomin A was isolated from dinoflagellate Alexandrium hiranoi as an antifungal agent by Murakami in 1988. Later, its particular bioactivities, such as modulation of actomyosin ATPase activities, increasing the filamentous Although its detailed NMR data and unique planer structure featured by a 32-membered macrolactone including 5- and 6-membered cyclic ethers (the A-,据报道，d和e-ring零件），螺旋环乙酸（BC环部件）和6元的环状半骨（F-Ring部分），Goniodomin a的立体化学尚不清楚。从鞭毛藻二烷酸酯sp.s1中分离了加勒比诺酯I，更多的-36-5作为细胞毒性剂，其在1995年通过Shimizu表现出强烈的细胞毒性对HCT116，IC_ <50> 1.6 nm的IC_ <50>，其策略结构。阐明了环氧化物和5个羟基（包括半羟基组），尚未确定其相对和绝对构型。从该研究项目中，确定部分立体化学和促性腺素A的部分合成如下：（1）从穆拉卡米（Murakami）报道的A-，BC-，D-，E-和F-RIND部分的A-，BC-，D-，E-和F-RIND部件的相对构型是根据Murakami A报告的NMR数据的；（2）合成了具有预测的立体体的A-，D-，E-和F-Ring段；（3）天然Goniodomin A的NMR数据与合成A-，D，E-和F-Ring段的NMR数据一致；（4）通过比较自然促性腺素A的NMR数据与宏环中包含的合成脱环确定了脱环部分的相对立体化学；（5）通过从GoniodominA的NMR数据中对预测结构进行合成评估，可以阐明BC环部分的正确立体化学化学化学化学化学化学。较少的

项目成果

期刊论文数量（58）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Convergent synthesis of the ABCDE-ring part of ciguatoxin CTX3C

雪卡毒素 CTX3C ABCDE 环部分的收敛合成

DOI：
发表时间：
2004
期刊：
Tetrahedron Letters 45
影响因子：
0
作者：
Setsuko Komatsu;Hiroyuki Yano;Kenshu Fujiwara
通讯作者：
Kenshu Fujiwara

Synthesis of the common left-half part of pectenotoxins.

果胶毒素常见左半部分的合成。

DOI：
发表时间：
2005
期刊：
Tetrahedron Lett. 46(30)
影响因子：
0
作者：
Kenshu Fujiwara;Masanori Kobayashi;Fuyuki Yamamoto;Yu-ichi Aki;Mariko Kawamura;Daisuke Awakura;Seiji Amano;Azusa Okano;Akio Murai;Hidetoshi Kawai;Takanori Suzuki
通讯作者：
Takanori Suzuki

Formal total synthesis of hemibrevetoxin B by a convergent strategy