Two-Phase Synthesis of Taxol.

Two-Phase Synthesis of Taxol.
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DOI:
10.1021/jacs.0c03592
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发表时间:
2020-06-10
影响因子:
15
通讯作者:
Baran PS
Baran PS
中科院分区:
化学1区
文献类型:
--
作者:
Kanda Y;Nakamura H;Umemiya S;Puthukanoori RK;Murthy Appala VR;Gaddamanugu GK;Paraselli BR;Baran PS

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紫杉醇®被广泛认为是迄今发现的最著名的天然菌株之一,并已成为基础和应用科学中无数研究的主题。它作为抗癌剂取得了有据可查的成功,再加上早期对供应的担忧,促使全球化学家进行了激烈的努力,通过全合成为其制备提供了解决方案。这些开创性的研究证明了后合成导向获得合成紫杉醇的可行性,尽管数量很少,而且需要付出巨大的努力。在实践中,所有的药物化学努力和最终的商业化都依赖于天然的(植物材料)或生物合成衍生的(合成生物学)供应。在这里,我们展示了一种互补的发散合成方法,这种方法是在生物合成萜类合成设备的基础上整体仿制而成的,可以用来实现紫杉醇®。
Taxol® is widely regarded as amongst the most famed natural isolates ever discovered, and has been the subject of innumerable studies in both basic and applied science. Its documented success as an anticancer agent, coupled with early concerns over supply, stimulated a furious worldwide effort from chemists to provide a solution for its preparation through total synthesis. Those pioneering studies proved the feasibility of retrosynthetically-guided access to synthetic Taxol, albeit in minute quantities and with enormous effort. In practice, all medicinal chemistry efforts and eventual commercialization have relied upon natural- (plant material) or biosynthetically-derived (synthetic biology) supplies. Here we show how a complementary divergent synthetic approach that is holistically patterned off of biosynthetic machinery for terpene synthesis can be used to arrive at Taxol®.
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