Synthesis of the Spiroketal Domains of Spirastrellolide

螺菌内酯螺酮结构域的合成

• 批准号: 7110613
• 负责人: KEVIN P COLE
• 金额: $ 4.6万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7110613
• 关键词: biological products; cell cycle; neoplasm /cancer; phosphatase inhibitor; phosphoprotein phosphatase; stereochemistry; stereoisomer

DESCRIPTION (provided by applicant): Spirastrellolide A is a complex marine natural product that has been shown to be a highly potent inhibitor of protein phosphatase 2A. Much like the well-known Ser/Thr phosphatase inhibitors fostriecin and okadaic acid, spirastrellolide causes premature entry into mitosis and mitotic arrest and is thus, a potential theraputic against various forms of cancer. There are however, many questions regarding the actual structure of spirastrellolide (absolute and relative stereochemistries, pharmacaphore etc.) which to date have not been answered through isolation/degredation and could likely be answered by total synthesis. The structural complexity of spirastrellolide is high, so the total synthesis would require a tremendous effort; we are proposing the stereoselective synthesis of the two spiroketal domains, and go on to suggest a general strategy with which the two pieces can be united, and the total synthesis completed.

描述（由申请人提供）：螺环内酯A是一种复杂的海洋天然产物，已被证明是蛋白磷酸酶2A的高效抑制剂。与众所周知的丝氨酸/苏氨酸磷酸酶抑制剂fostriecin和冈田酸非常相似，螺旋霉素导致过早进入有丝分裂和有丝分裂停滞，因此是一种潜在的治疗各种形式的癌症的药物。然而，关于螺环内酯的实际结构（绝对和相对立体化学，药效学等）存在许多问题。到目前为止还没有通过分离/降解来回答，并且可能通过全合成来回答。spirastrelllestine的结构复杂性高，所以全合成将需要巨大的努力，我们提出的立体选择性合成的两个螺缩酮结构域，并继续建议一个一般的策略，这两个部分可以联合起来，全合成完成。