Harvard Department of Chemistry and Chemical Biology, 12 Oxford Street, Box 408, Cambridge, Massachussetts 02138, USA.
Nat Chem. 2010 Oct;2(10):886-92. doi: 10.1038/nchem.794. Epub 2010 Aug 1.
The cortistatins are a recently identified class of marine natural products characterized by an unusual steroidal skeleton, which have been found to inhibit differentially the proliferation of various mammalian cells in culture by an unknown mechanism. We describe a comprehensive route for the synthesis of cortistatins from a common precursor, which in turn is assembled from two fragments of similar structural complexity. Cortistatins A and J, and for the first time K and L, have been synthesized in parallel processes from like intermediates prepared from a single compound. With the identification of facile laboratory transformations linking intermediates in the cortistatin L synthetic series with corresponding intermediates to cortistatins A and J, we have been led to speculate that somewhat related paths might occur in nature, offering potential sequencing and chemical detail for cortistatin biosynthetic pathways.
考替他汀是一类最近被鉴定的海洋天然产物，其特征是具有不寻常的甾体骨架，通过未知机制被发现能够在培养的各种哺乳动物细胞中差异抑制增殖。我们描述了一种从共同前体制备考替他汀的综合途径，该前体又由两个结构相似的片段组装而成。考替他汀 A 和 J，以及首次合成的 K 和 L，都从类似的中间体平行合成，这些中间体是由单个化合物制备的。通过识别在考替他汀 L 合成系列的中间体与考替他汀 A 和 J 的相应中间体之间的易于进行的实验室转化，我们推测在自然界中可能存在稍微相关的途径，为考替他汀生物合成途径提供了潜在的序列和化学细节。
