权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Molecular Scientific Research on Cytotoxic Oxasqualenoids Based on Chemical Synthesis

基于化学合成的细胞毒性氧杂鲨烯类化合物的分子科学研究

基本信息

批准号：
17510180
负责人：
MORIMOTO Yoshiki
金额：
$ 2.44万
依托单位：
Osaka City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

项目摘要

Recently, highly oxidized and structurally diverse triterpene polyethers, which are thought to be biogenetically squalene-derived natural products (oxasqualenoids), have been isolated from both marine and terrestrial organisms. However, it is often difficult to determine their stereostructures even by the current, highly advanced spectroscopic methods, especially in acyclic systems including stereogenic quaternary carbon centers such as those in oxasqualenoids. In such cases, it is effective to predict and synthesize the possible stereostructures. Herein, we report total assignments of the previously incomplete stereostructures of intricatetraol, enshuol, and aurilol, members of the oxasqualenoids, through the chemical syntheses of the natural products, the configurations of which are difficult to determine by other means.Intricatetraol and enshuol were isolated from the red algae Laurencia intricata and omaezakiana Masuda by Suzuki and co-workers in 1993 and 1995, respectively, and th … More e crude fraction including intricatetraol exhibited cytotoxicity against P388 with IC<50> of 12.5 μg/mL. Although the planar structures and partial configurations were elucidated by spectroscopic and chemical analyses, until now the entire configurations had not been determined. We have accomplished the total assignments of the previously incomplete stereostructures of (+)-intricatetraol and (+)-enshuol through the first asymmetric total syntheses.Aurilol was isolated from the sea hare, Dolabella auricularia, by Yamada et al. in 1998 and exhibited cytotoxicity against HeLa S_3 cells with IC_<50> of 4.3 μg/mL. Although the plane structure and partial stereochemistry were also elucidated by spectroscopic and chemical analyses, determination of the entire stereochemistry has not been reached. We have accomplished the first asymmetric total synthesis of (+)-aurilol featuring the highly regio- and stereocontrolled biogenetic-like A-D ether ring formations. The total synthesis has realized the total assignment of the incomplete stereostructure of aurilol.During these syntheses, we found that the switching of the usual 5-exo cyclizations of epoxide substrates to the 6-endo mode, which goes against Baldwin rule, is demonstrated by treating bishomoepoxy alcohols with triisopropylsilyl triflate (TIPSOTf) in nitromethane. This method is diffarent to those previously reported in which elaborate modifications of the epoxide substrate are required to attain 6-endo cyclization. The 6-endo cyclization was successfully applied to the B ring formation in enshuol and aurilol. Less

最近，高度氧化和结构多样的三萜聚醚，这被认为是生物角鲨烯衍生的天然产物（oxasqualene），已被分离出的海洋和陆地生物。然而，即使通过目前高度先进的光谱方法，通常也难以确定它们的立体结构，特别是在包括立体季碳中心的无环系统中，例如oxasqualcine中的那些。在这种情况下，预测和合成可能的立体结构是有效的。本文报道了氧化角鲨烷属化合物intricatetraol、enshuol和auriol的不完全立体结构的全归属，这些化合物是Suzuki及其同事分别于1993年和1995年从红藻凹顶藻Laurencia intricata和omaezakiana增田中分离得到的。和th ...更多信息结果表明，含intertricatetraol的粗品组分对P388细胞有较强的杀伤作用，IC<50>为12.5 μg/mL。虽然通过光谱和化学分析阐明了其平面结构和部分构型，但迄今为止尚未确定其全部构型。1998年Yamada等从海兔Dolabella auricularia中分离得到的（+）-intertricatetraol和（+）-enshuol对HeLa S_3细胞有明显的细胞毒作用，<50>IC_2为4.3 μg/mL。虽然平面结构和部分立体化学也阐明了光谱和化学分析，确定整个立体化学还没有达到。我们完成了第一个不对称全合成的（+）-aurilol具有高度区域和立体控制的生物类A-D醚环的形成。在这些合成中，我们发现在硝基甲烷中用三氟甲磺酸三异丙基硅酯（TIPSOTf）处理双环氧醇时，环氧底物通常的5-外环化转变为6-内环化，这违反了Baldwin规则。该方法不同于先前报道的那些方法，其中需要对环氧化物底物进行精心修饰以获得6-内环化。6-内环化反应成功地应用于恩硕和奥瑞洛尔的B环的形成。少