Ota Yusuke, Murayama Toshiki, Nozaki Kyoko
Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
Proc Natl Acad Sci U S A. 2016 Mar 15;113(11):2857-61. doi: 10.1073/pnas.1518898113. Epub 2016 Feb 23.
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.
在自然界中，许多复杂结构是通过一系列特定的酶催化反应由简单分子组装而成的。一个典型的例子是脱氧丙酸基序，它是一种含有多个手性中心的交替甲基化烷基链，由简单的构建单元通过一系列酶促反应生物合成。然而，在有机合成中，大多数已报道的路线都需要合成复杂的构建单元。此外，每次延长都需要进行多步反应并进行单独纯化。在此，我们展示了从丙烯一步构建脱氧丙酸结构，以实现三步合成（2R,4R,6R,8R）-2,4,6,8-四甲基癸酸，这是灰雁尾脂腺蜡的一种主要酸性成分。为实现这一策略，我们专注于配位链转移聚合，并优化反应条件以得到立体控制的低聚物，这与迄今为止开发的其他合成策略形成对比，后者每单元需要3至6步，且不可避免地会产生副产物。此外，从一批产物中分离出了具有不同脱氧丙酸单元数目的多种低聚物，这表明该方法可应用于构建文库。我们的策略为通向其他具有脱氧丙酸基序的天然产物的简便合成路线打开了大门。
