Han Bing Yuan, Lam Nelson Y S, MacGregor Callum I, Goodman Jonathan M, Paterson Ian
University Chemical Laboratory, Lensfield Road, Cambridge, CB2 1EW, UK.
Chem Commun (Camb). 2018 Mar 27;54(26):3247-3250. doi: 10.1039/c8cc00933c.
Through synthesising both candidate diastereomers of a model C1-C28 fragment of the potent cytotoxic marine polyketide hemicalide, an assignment of the relative configuration between the C1-C15 and C16-C26 regions has been achieved. By detailed NMR comparisons with the natural product, the relative stereochemistry between these two 1,6-related stereoclusters is elucidated as 13,18-syn rather than the previously proposed 13,18-anti relationship. A flexible and modular strategy using an advanced C1-C28 ketone fragment 22 is outlined to elucidate the remaining stereochemical features and achieve a total synthesis.
通过合成强效细胞毒性海洋聚酮化合物hemicalide的模型C1 - C28片段的两种候选非对映异构体，实现了C1 - C15和C16 - C26区域之间相对构型的确定。通过与天然产物进行详细的核磁共振比较，阐明了这两个1,6相关立体簇之间的相对立体化学为13,18 - 顺式，而非先前提出的13,18 - 反式关系。概述了一种使用先进的C1 - C28酮片段22的灵活且模块化的策略，以阐明其余的立体化学特征并实现全合成。
