Synthesis of the Spiroketal Domains of Spirastrellolide

说明书(申请人提供)：螺内酯A是一种复杂的海洋天然产物，已被证明是一种高度有效的蛋白磷酸酶2A抑制剂。就像著名的丝氨酸/苏氨酸磷酸酶抑制剂Fostriecin和冈田酸一样，螺列酯会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，关于螺雷内酯的实际结构(绝对和相对立体化学、药效等)仍有许多问题。到目前为止还没有通过分离/脱脂来回答，而很可能通过全合成来回答。螺内酯的结构复杂性很高，所以全合成需要付出巨大的努力；我们建议对两个螺酮结构域进行立体选择性合成，并提出了一个将两个片断结合在一起的一般策略，完成了全合成。

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.