One-step catalytic asymmetric synthesis of all-/syn/deoxypropionate motif from propylene: Total synthesis of (-)tetramethyldecanoic acid
One-step catalytic asymmetric synthesis of all-/syn/deoxypropionate motif from propylene: Total synthesis of (-)tetramethyldecanoic acid
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从丙烯一步催化不对称合成全/顺式/脱氧丙酸酯基序：(-)四甲基癸酸的全合成
DOI：
10.1073/pnas.1518898113
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Kyoko Nozaki
中科院分区：
文献类型：
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作者：
Yusuke Ota;Toshiki Murayama;Kyoko Nozaki
在自然界中，许多复杂的结构是由简单分子通过一系列定制的酶催化反应组装而成的。一个代表性的例子是脱氧丙酸基序，一个交替甲基化的烷基链含有多个立体中心，这是生物合成的一系列酶促反应从简单的积木。然而，在有机合成中，大多数报道的路线需要合成复杂的结构单元。此外，在每次延伸时需要具有单独纯化的多步反应。在这里，我们展示了从丙烯在一个单一的步骤中的脱氧丙酸酯结构的建设，以实现三步合成（2 R，4 R，6 R，8 R）-2，4，6，8-四甲基癸酸，一个主要的酸成分的一个preen腺蜡的灰雁。为了实现这一策略，我们重点研究了配位链转移聚合，并优化了反应条件，以提供立体控制的低聚物，这与迄今为止开发的其他合成策略不同，这些策略需要3-6个步骤/单元，不可避免地产生副产物。此外，从一个批次中分离出具有不同数目的脱氧丙酸酯单元的多个寡聚体，显示了对文库构建的应用。我们的策略打开了大门，为其他天然产品，共享脱氧丙酸基序的简易合成路线。
In nature, many complex structures are assembled from simple molecules by a series of tailored enzyme-catalyzed reactions. One representative example is the deoxypropionate motif, an alternately methylated alkyl chain containing multiple stereogenic centers, which is biosynthesized by a series of enzymatic reactions from simple building blocks. In organic synthesis, however, the majority of the reported routes require the syntheses of complex building blocks. Furthermore, multistep reactions with individual purifications are required at each elongation. Here we show the construction of the deoxypropionate structure from propylene in a single step to achieve a three-step synthesis of (2R,4R,6R,8R)-2,4,6,8-tetramethyldecanoic acid, a major acid component of a preen-gland wax of the graylag goose. To realize this strategy, we focused on the coordinative chain transfer polymerization and optimized the reaction condition to afford a stereo-controlled oligomer, which is contrastive to the other synthetic strategies developed to date that require 3–6 steps per unit, with unavoidable byproduct generation. Furthermore, multiple oligomers with different number of deoxypropionate units were isolated from one batch, showing application to the construction of library. Our strategy opens the door for facile synthetic routes toward other natural products that share the deoxypropionate motif.