Fostriecin and Related Protein Phosphatase Inhibitors

描述(申请人提供)：一项对福斯特列星的详细研究，一种有效的 和有效的抗肿瘤药物，抑制有丝分裂进入检查点 通过选择性抑制蛋白磷酸酶2A和4，以及相关的 天然的和人工合成的蛋白磷酸酶(PP)抑制剂将 被引导了。这将包括实施一项改进的 第二代Fostriecin的全合成、全合成和 细胞抑素的立体化学归属、全合成和 舒曲菌素的立体化学归属。将研究范围扩大到 福司他汀药效团的定义 选择性PP缓蚀剂及制备更稳定、更有结构的PP 更简单的类似物，解决目前限制临床潜力的问题 福斯特里西林的研究将继续进行。

DESCRIPTION (provided by applicant): A detailed study of fostriecin, a potent and efficacious antitumor agent that inhibits the mitotic entry checkpoint through the selective inhibition of protein phosphatases 2A and 4, and related naturally-occurring and synthetic inhibitors of protein phosphatases (PP) will be conducted. This will include the implementation of an improved second-generation total synthesis of fostriecin, the total synthesis and stereochemical assignment of cytostatin, and the total synthesis and stereochemical assignment of sultriecin. Extensions of the studies to the definition of the fostriecin pharmacophore responsible for its potent and selective PP inhibition and the preparation of more stable and structurally simpler analogues that address issues currently limiting the clinical potential of fostriecin will be pursued.