Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania, 15260, USA.
Chemistry. 2018 Nov 2;24(61):16271-16275. doi: 10.1002/chem.201804417. Epub 2018 Oct 9.
A diverted total synthesis effort is described that is designed to prepare potent cytotoxins based on the actin-binding natural product bistramide A. The major focus of this study is the preparation of analogues that contain oxygenation at the C29 position, which is necessary for a key reaction in the sequence but is not present in the natural product. This process showed that C29 ketone analogues are accessed more readily and show similar potency compared to the natural product. The ability to incorporate C29 oxygenation and to replace a secondary alcohol by a primary alcohol allowed for the development of a more convergent approach that provides a potent analogue in just eight steps in its longest linear sequence.
描述了一种经转换的全合成方法，旨在基于肌动蛋白结合天然产物 bistramide A 来制备有效的细胞毒素。本研究的主要重点是制备含有 C29 位置氧化的类似物，这是该序列中一个关键反应所必需的，但在天然产物中不存在。该过程表明，C29 酮类似物更容易获得，并且与天然产物相比具有相似的效力。能够引入 C29 氧化并将仲醇取代为伯醇，使得可以开发出一种更具收敛性的方法，该方法在其最长线性序列的仅八个步骤中提供了一种有效的类似物。
