Preparation of a Solid-Phase Polyketide Synthase Mimic

描述（由申请人提供）：聚酮化合物代表一类对人类状况产生巨大影响的小分子。这类天然产物和衍生物具有丰富的药理学性质，从抗癌到抗生素，甚至抗胆固醇活性。制备这些分子的标准方法包括发酵和全合成。该提案概述了一种新的方法，用于一般的聚酮化合物的合成，这是由聚酮化合物合酶的启发，在自然界中利用的酶机制，以制备这类分子。该方法将利用固体支撑的模板的使用，以通过硫酯之间的脱羧Claisen反应来延长生长的聚酮链。如果成功，这种方法可以为合成聚酮化合物的迭代标准化方法奠定基础，为天然产物及其衍生物的自动合成开辟途径。

DESCRIPTION (provided by applicant): Polyketides represent a class of small molecules that has had an enormous impact on the human condition. Several natural products and derivatives of this class possess a wealth of pharmacological properties from anti-cancer to antibiotic and even anti-cholesterol activity. Standard methods to prepare these molecules include fermentation and total synthesis. This proposal outlines a new method for the general synthesis of polyketides that is inspired by polyketide synthase, the enzymatic machinery that is utilized in Nature to prepare molecules of this class. This method would capitalize on the use of a solid-supported template to elongate a growing polyketide chain via decarboxylative Claisen reactions between thioesters. If successful, this method could lay the groundwork for an iterative, standardized method for the synthesis polyketides, opening avenues for automated synthesis of natural products and derivatives thereof.