School of Chemistry, University of Bristol, Cantock's Close, Bristol BS8 1TS, UK.
Nat Chem. 2017 Sep;9(9):896-902. doi: 10.1038/nchem.2757. Epub 2017 Apr 10.
The polypropionate motif is ubiquitous, being characteristic of the most important family of natural products for human health, the polyketides. Numerous strategies have been devised to construct these molecules with high stereocontrol, but certain stereoisomers remain challenging to prepare. We now describe the development of an iterative assembly line strategy for the construction of polypropionates. An assembly line strategy for the synthesis of deoxypolypropionates has already been described. However, the introduction of carbinol units required the development of new building blocks and new reaction conditions. This has been achieved by the use of enantioenriched lithiated α-chlorosilanes [1-((2'-lithiochloromethyldimethylsilyl)-methyl)-2-(methoxymethyl)-pyrrolidine], thus enabling the programmed synthesis of polypropionates in a fully stereocontrolled manner, including the stereochemically challenging anti-anti isomers. The versatility of the approach is exemplified in its extension to the synthesis of 1,3-related polyols. The methodology now allows access to a much wider family of polyketide natural products with stereochemistry being dialled in at will.
聚丙酸盐基序无处不在，是对人类健康最重要的天然产物家族——聚酮类的特征。人们设计了许多策略来构建具有高立体选择性的这些分子，但某些立体异构体仍然难以制备。我们现在描述了一种用于构建聚丙酸盐的迭代装配线策略的开发。已经描述了用于合成去氧聚丙酸盐的装配线策略。然而，引入手性碳原子需要开发新的构建块和新的反应条件。通过使用对映体富集的锂化α-氯硅烷[1-((2'-锂代氯甲基二甲基硅基)-甲基)-2-(甲氧基甲基)-吡咯烷]实现了这一点，从而能够以完全立体控制的方式程序化合成聚丙酸盐，包括立体化学上具有挑战性的反式反式异构体。该方法的多功能性在其扩展到 1,3 相关多元醇的合成中得到了例证。该方法现在可以获得更广泛的聚酮类天然产物家族，其立体化学可以随意调节。
