title: Total synthesis of (+)-gelsemine via an organocatalytic Diels-Alder approach.
abstract: 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%.
authors.affiliation: 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.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Shengguo
authors.initials: S
authors.lastname: Duan
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Tao
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Zhai
authors.affiliation: 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.
authors.forename: Fayang G
authors.initials: FG
authors.lastname: Qiu
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis*; D061565:Cycloaddition Reaction; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids; C063230:gelsemine