Original and practical total syntheses of antitumor natural products

通过2h -吡喃衍生物的仿生二聚化，合成了环氧喹啉A、B、C和环氧双酚A。前三种天然产物均由Diels-Alder反应得到，而后者则由形式的4+4环加成反应合成，这是一种非常罕见的反应。我们通过从头计算研究了这种4+4环加成的反应机理，发现该反应是通过双基机制进行的。我们还合成了一些具有较强生物活性的天然产物，如lucilactaene、synerazol、pseurotin A、RK-805、fumagillol、FR65814、ovalicin、5- demethyllovalicin、EI-1941-1、EI-1941-2、EI-1941-3、panepophenthrin、nikkomycin B、fostriecin。在这些合成过程中，我们利用有机催化剂开发了几种实用的不对称反应，如在水存在下的直接醛醇反应、Mannich反应、羰基化合物的α-氨基氧化反应和Michael反应。

We have synthesized epoxyquinol A, B, C and epoxytwinol A, by the biomimetic dimerization of 2H-pyran derivatives. The former three natural products were derived by the Diels-Alder reaction, while the latter was synthesized by the formal 4+4 cycloaddition reaction, which is a very rare reaction. We have investigated the reaction mechanism of this 4+4 cycloaddition via ab initio calculation and found that the reaction would proceed via a biradical mechanism. We have also synthesized several natural products with strong biological activities, such as lucilactaene, synerazol, pseurotin A, RK-805, fumagillol, FR65814, ovalicin, 5-demethylovalicin, EI-1941-1, EI-1941-2, EI-1941-3, panepophenanthrin, nikkomycin B, and fostriecin. During these syntheses, we developed several practical asymmetric reactions using oragnocatalysts such as direct aldol reaction in the presence of water, Mannich reaction, α-aminoxylation of carbonyl compounds, and Michael reaction.