Denmark S E, Cottell J J
Roger Adams Laboratory, Department of Chemistry, University of Illinois, Urbana, Illinois 61801, USA.
J Org Chem. 2001 Jun 15;66(12):4276-84. doi: 10.1021/jo0101510.
A highly efficient total synthesis of (+)-1-epiaustraline ((+)-1), a tetrahydroxypyrrolizidine alkaloid of the alexine/australine subclass, is described. The key step is a tandem intramolecular [4 + 2]/intermolecular [3 + 2] nitroalkene cycloaddition involving dienylsilyloxy nitroalkene 3 and chiral vinyl ether 4, which establishes four of the five stereocenters present. The final center was installed by a diastereoselective dihydroxylation. Hydrogenolytic unmasking of the nitroso acetal tosylate 17 containing the silyl ether linkage was thwarted by a slow alkylation and an undesired Peterson-type elimination. Prior removal of the silicon moiety by Tamao-Fleming oxidation proceeded in excellent yield and provided a substrate suitable for hydrogenolysis and deprotection. The complete synthesis required only 10 steps to deliver the (+)-1-epiaustraline in 7.0% overall yield.
本文描述了一种高效全合成（+）-1-表澳洲茄碱（（+）-1）的方法，（+）-1是阿列辛/澳洲茄碱亚类的一种四羟基吡咯里西啶生物碱。关键步骤是涉及二烯基甲硅烷氧基硝基烯烃3和手性乙烯基醚4的串联分子内[4 + 2]/分子间[3 + 2]硝基烯烃环加成反应，该反应构建了五个立体中心中的四个。最后一个中心通过非对映选择性二羟基化反应引入。含有甲硅烷基醚键的亚硝基缩醛对甲苯磺酸酯17的氢解去保护反应因烷基化反应缓慢和不期望的彼得森型消除反应而受阻。通过玉尾-弗莱明氧化法预先除去硅部分，反应产率极高，并提供了适合氢解和脱保护的底物。完整的合成仅需10步，以7.0%的总产率得到（+）-1-表澳洲茄碱。
