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lgq101木虫 (小有名气)
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[求助]
求翻译！！！急~~~谢谢
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| Alkaloid and terpenoid natural products display an extensive array of chemical frameworks and biological activities. However such scaffolds remain underrepresented in current screening collections and are, thus, attractive targets for the synthesis of natural product-based libraries that access underexploited regions of chemical space. Recently, we reported a systematic approach to the stereoselective synthesis of multiple alkaloid/terpenoid-like scaffolds using transition metal-mediated cycloaddition and cyclization reactions of enyne and diyne substrates assembled on a tert-butylsulfinamide lynchpin. We report herein the synthesis of a 190-membered library of alkaloid/terpenoid-like molecules using this synthetic approach. Translation to solid-phase synthesis was facilitated by the use of a tert-butyldiarylsilyl (TBDAS) linker that closely mimics the tert-butyldiphenysilyl protecting group used in the original solution-phase route development work. Unexpected differences in stereoselectivity and regioselectivity were observed in some reactions when carried out on solid support. Further, the sulfinamide moiety could be hydrolyzed or oxidized efficiently without compromising the TBDAS linker to provide additional amine and sulfonamide functionalities. Principal component analysis of the structural and physicochemical properties of these molecules confirmed that they access regions of chemical space that overlap with bona fide natural products and are distinct from areas addressed by conventional synthetic drugs and drug-like molecules. The influences of scaffolds and substituents were also evaluated, with both found to have significant impacts on location in chemical space and three-dimensional shape. Broad biological evaluation of this library will provide valuable insights into the abilities of natural product-based libraries to access similarly underexploited regions of biological space. |
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zuodg
铁杆木虫 (正式写手)
有为青年
- 翻译EPI: 180
- 应助: 5 (幼儿园)
- 贵宾: 0.015
- 金币: 6765.2
- 散金: 48
- 红花: 18
- 帖子: 500
- 在线: 285.5小时
- 虫号: 1055187
- 注册: 2010-07-10
- 性别: GG
- 专业: 外国语言
【答案】应助回帖
★
sltmac(金币+1): 谢谢应助~~ 2011-05-31 15:26:31
lgq101(金币+40, 翻译EPI+1): 谢谢 2011-05-31 21:17:58
sltmac(金币+1): 谢谢应助~~ 2011-05-31 15:26:31
lgq101(金币+40, 翻译EPI+1): 谢谢 2011-05-31 21:17:58
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生物碱和萜类天然产物具有一些列丰富的化学结构和生物活性。 然而目前这些结构骨架在筛选时还没有受到足够的重视，因此是化学合成天然产物文库、探索未知化学空间的魅力靶标。 最近，我们报道了一个使用过渡态金属介导炔、二炔底物（装配在t-丁基磺胺上）环加成与环化、通过立体化学系统合成多个生物碱/萜类结构骨架的研究。使用该合成方法我们合成一个包含190种化合物的生物碱/萜类化合物文库。固态合成借助于TBDAS链接分子（该分子与液态合成所用的t-丁基磺胺保护集团很类似）。固态合成发现有些反应的立体选择性与区位选择性不相同。此外，磺胺基团会发生高效水解或氧化，不能继续提供胺基与磺胺基。对文库分子的结构性质与理化性质进行分析发现， 这些分子的化学空间与天然产物有重叠，与传统合成药物或药物类似物分子的化学空间不同。化学结构骨架与取代基的影响也进行了评估，发现对化学空间的定位与三级结构有显著影响。文库生物活性的评估对于基于天然产物的文库探索未探索生物空间具有重要价值。 |
2楼2011-05-31 13:34:09