剪接抑制素E的对映选择性合成及生物活性评价。

Ghosh Arun K, Veitschegger Anne M, Sheri Venkata Reddy, Effenberger Kerstin A, Prichard Beth E, Jurica Melissa S

†Department of Chemistry and Department of Medicinal Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, United States.

‡Department of Molecular Cell and Developmental Biology and Center for Molecular Biology of RNA, University of California, Santa Cruz, California 95064, United States.

Org Lett. 2014 Dec 5;16(23):6200-3. doi: 10.1021/ol503127r. Epub 2014 Nov 25.

An enantioselective total synthesis of spliceostatin E has been accomplished. The δ-lactone unit A was constructed from readily available (R)-glycidyl alcohol using a ring-closing olefin metathesis as the key reaction. A cross-metathesis of ring A containing δ-lactone and the functionalized tetrahydropyran B-ring provided spliceostatin E. Our biological evaluation of synthetic spliceostatin E revealed that it does not inhibit splicing in vitro and does not impact speckle morphology in cells. Spliceostatin E was reported to possess potent antitumor activity.

已完成剪接抑制素E的对映选择性全合成。δ-内酯单元A由易于获得的(R)-缩水甘油醇构建，以闭环烯烃复分解反应作为关键反应。含δ-内酯的A环与功能化的四氢吡喃B环进行交叉复分解反应得到剪接抑制素E。我们对合成的剪接抑制素E的生物学评估表明，它在体外不抑制剪接，对细胞中的斑点形态也没有影响。据报道，剪接抑制素E具有强大的抗肿瘤活性。