Faculty of Chemistry, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece.
J Org Chem. 2012 Nov 2;77(21):9659-67. doi: 10.1021/jo301662e. Epub 2012 Oct 18.
The total synthesis of the structure assigned to the natural product phaeosphaeride A 1a was accomplished. The key steps involve the addition of vinyllithium reagent 7 to the acetonide-protected aldehyde 8 to access the carbon backbone of 1a, the introduction of the methoxylamino group followed by intramolecular hetero-Michael cyclization, and methanol elimination to form the dihydropyran ring. In this study, both enantiomers of 1a were synthesized and tested for biological activity. Preliminary results showed that (6R,7R,8R)-1a and (6S,7S,8S)-1a inhibit STAT3-dependent transcriptional activity in a dose-dependent manner and exhibit antiproliferative properties in breast (MDA-MB-231) and pancreatic (PANC-1) cancer cells.
天然产物 phaeosphaeride A 1a 的结构的全合成已经完成。关键步骤包括将乙烯基锂试剂 7 添加到保护的醛 8 中，以获得 1a 的碳骨架，引入甲氧基氨基后进行分子内杂迈克尔环化，以及甲醇消除以形成二氢吡喃环。在这项研究中，1a 的两种对映异构体都被合成并进行了生物活性测试。初步结果表明，(6R,7R,8R)-1a 和 (6S,7S,8S)-1a 以剂量依赖的方式抑制 STAT3 依赖性转录活性，并在乳腺癌 (MDA-MB-231) 和胰腺 (PANC-1) 癌细胞中表现出抗增殖特性。
