Protonated montmorillonite-mediated highly specific isomerization of oleanolic acid esters: application to the synthesis of Δ13(18)-CDDO-Me.
A one-pot highly specific isomerization of oleanolic acid esters (5a-g) to δ-oleanolic acid esters (6a-g) was achieved in the presence of proton-exchanged montmorillonite (H-mont) under mild reaction conditions. This protocol could proceed smoothly on a 15.0 gram scale. Based on this methodology, the synthesis of the biologically active compound Δ13(18)-CDDO-Me (4) was realized.
Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease and State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, China. hongbinsun@cpu.edu.cn wxagj@126.com and Department of Medicinal Chemistry, School of Pharmacy, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China.
Dongyin
D
Chen
Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease and State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, China. hongbinsun@cpu.edu.cn wxagj@126.com.
Pu
P
Zhang
Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease and State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, China. hongbinsun@cpu.edu.cn wxagj@126.com.
Yan
Y
Sun
Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease and State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, China. hongbinsun@cpu.edu.cn wxagj@126.com.
Pengfei
P
Wang
Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease and State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, China. hongbinsun@cpu.edu.cn wxagj@126.com.
Can
C
Zhang
Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease and State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, China. hongbinsun@cpu.edu.cn wxagj@126.com.
Lingyi
L
Kong
Department of Physical Chemistry, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, China. jzhangcpu@126.com.
Ji
J
Zhang
Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease and State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, China. hongbinsun@cpu.edu.cn wxagj@126.com.
Hongbin
H
Sun
Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease and State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, China. hongbinsun@cpu.edu.cn wxagj@126.com.
Xiaoan
X
Wen
D001546:Bentonite / Q000737:chemistry*; D060326:Chemistry Techniques, Synthetic; D004952:Esters / Q000737:chemistry*; D007536:Isomerism; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*; D011522:Protons
D004952:Esters; D011522:Protons; D001546:Bentonite; D009828:Oleanolic Acid; C445068:bardoxolone methyl