Total Synthesis of Antitumor Agent Eupenifeldin

描述(申请人提供)：自然界是各类抗肿瘤化合物的重要来源。最近，从短毛真球藻ATCC 74184的发酵液中分离到一种新的细胞毒性双环蛋白Eupenifeldin。初步实验表明，优苯非菌素对人结肠癌细胞株HCT-116和人结肠癌细胞株HCT-VM4有较强的体外毒性，其IC50值分别为5 ng/ml和2 ng/ml。下面的建议描述了标题化合物的高度收敛和对映选择性的全合成。关键步骤包括同时将两个特罗普隆单元引入到十一元核心，以及在一步中两个二氢吡喃环的立体选择性形成。如果成功，建议的路线将为进一步的生物学评价提供大量的天然产物，以及为结构-活性关系研究制备其他非天然类似物的可能性。

DESCRIPTION (provided by applicant): Nature is an important souce of various types of antitumor compounds. Recently a novel cytotoxic bistropolone Eupenifeldin was isolated from a culture broth produced by Eupenicillium brefeldianum ATCC 74184. Preliminary testing shows that Eupenifeldin is highly toxic in vitro against HCT-116 and HCT-VM4(human colon carcinoma) cell lines, with IC50 values of 5 ng/ml and 2 ng/ml, respectively. The following proposal describes a highly convergent and enantioselective total synthesis of the title compound. The key steps include the simultaneous introduction of both tropolone units to the eleven-membered core, as well as the stereoselective formation of both dihydropyran rings in a single step. If successful, the proposed route will provide large amount of the natural prouct for further biological evaluation, as well as the possibility to prepare other non-natural analogues for structure-activity relationship studies.