Total syntheses of (-)-isoschizogamine and (-)-2-hydroxyisoschizogamine.
Total syntheses of (-)-isoschizogamine and (-)-2-hydroxyisoschizogamine are described. The synthesis employs two asymmetric Michael additions to establish chiral centers at C7 and the quaternary carbon C20. Regioselective reduction of the methylthioiminium cation rather than the enamine generates an isoschizogamine-type pentacyclic skeleton. Acidic hydrolysis of the isoschizogamine-type intermediate in the absence of oxygen provides natural (-)-isoschizogamine. Conducting the reaction in the presence of oxygen leads to a multistep oxidative hydrolysis cascade that affords unnatural (-)-2-hydroxyisoschizogamine.
Key Laboratory of Drug Targeting and Drug Delivery Systems of the Ministry of Education, West China School of Pharmacy and State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041 (P. R. China).
Xiaobei
X
Wang
Key Laboratory of Drug Targeting and Drug Delivery Systems of the Ministry of Education, West China School of Pharmacy and State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041 (P. R. China).
Dongliang
D
Xia
Key Laboratory of Drug Targeting and Drug Delivery Systems of the Ministry of Education, West China School of Pharmacy and State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041 (P. R. China).
Ling
L
Tan
Key Laboratory of Drug Targeting and Drug Delivery Systems of the Ministry of Education, West China School of Pharmacy and State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041 (P. R. China).
Huan
H
Chen
Key Laboratory of Drug Targeting and Drug Delivery Systems of the Ministry of Education, West China School of Pharmacy and State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041 (P. R. China).
Hongxiu
H
Huang
Key Laboratory of Drug Targeting and Drug Delivery Systems of the Ministry of Education, West China School of Pharmacy and State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041 (P. R. China).
Hao
H
Song
Key Laboratory of Drug Targeting and Drug Delivery Systems of the Ministry of Education, West China School of Pharmacy and State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041 (P. R. China). yongqin@scu.edu.cn.
Yong
Y
Qin
D001688:Biological Products; D002384:Catalysis; D026121:Indole Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D010084:Oxidation-Reduction; D013237:Stereoisomerism
C000607307:2-hydroxyisoschizogamine; D001688:Biological Products; D026121:Indole Alkaloids; C409122:isoschizogamine
Michael addition; asymmetric total synthesis; biogenetic pathway; isoschizogamine; oxidative hydrolysis