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.

中文翻译：

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具有完全立体控制的聚丙烯酸酯的迭代组装流水线合成

聚丙烯酸酯基序无处不在，是人类健康最重要的天然产物家族，即聚酮化合物。已经设计出许多策略来构建具有高度立体控制的这些分子，但是某些立体异构体仍然难以制备。现在，我们描述用于聚丙烯酸酯构造的迭代装配线策略的开发。已经描述了用于合成脱氧聚丙烯酸酯的流水线策略。但是，引入甲醇单元需要开发新的结构单元和新的反应条件。这是通过使用对映体富集的锂化α-氯硅烷[1-（（（2'-lithiochloromethyldimethylsilyl）-methyl）-2-（methoxymethyl）-pyrrolidine]，反–反异构体。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。现在，该方法学可以访问范围更广的聚酮化合物天然产品系列，并且可以随意拨打立体化学信息。