Chen Xiaoming, Duan Shengguo, Tao Cheng, Zhai Hongbin, Qiu Fayang G
1] State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China [2] Laboratory of Molecular Engineering, and Laboratory of Natural Product Synthesis, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, 190 Kaiyuan Boulevard, The Science Park of Guangzhou, Guangzhou 510530, China.
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China.
Nat Commun. 2015 May 21;6:7204. doi: 10.1038/ncomms8204.
The structurally complex alkaloid gelsemine was previously thought to have no significant biological activities, but a recent study has shown that it has potent and specific antinociception in chronic pain. While this molecule has attracted significant interests from the synthetic community, an efficient synthetic strategy is still the goal of many synthetic chemists. Here we report the asymmetric total synthesis of (+)-gelsemine, including a highly diastereoselective and enantioselective organocatalytic Diels-Alder reaction, an efficient intramolecular trans-annular aldol condensation furnishing the prolidine ring and establishing the configuration of the C20 quaternary carbon stereochemical centre. The entire gelsemine skeleton was constructed through a late-stage intramolecular SN2 substitution. The enantiomeric excess of this total synthesis is over 99%, and the overall yield is around 5%.
结构复杂的生物碱钩吻素甲以前被认为没有显著的生物活性，但最近的一项研究表明，它在慢性疼痛中具有强效且特异性的镇痛作用。虽然这种分子已引起合成领域的极大兴趣，但高效的合成策略仍是许多合成化学家的目标。在此，我们报道了（+）-钩吻素甲的不对称全合成，包括一个高度非对映选择性和对映选择性的有机催化狄尔斯-阿尔德反应、一个高效的分子内跨环羟醛缩合反应，该反应构建了脯氨酸环并确立了C20季碳立体化学中心的构型。整个钩吻素甲骨架通过后期分子内SN2取代构建而成。该全合成的对映体过量超过99%，总产率约为5%。
