Practical Synthesis of MDM2 Antagonist RG7388. Part 1: A Cu(II)-Catalyzed Asymmetric [3+2] Cycloaddition
Practical Synthesis of MDM2 Antagonist RG7388. Part 1: A Cu(II)-Catalyzed Asymmetric [3+2] Cycloaddition
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DOI：
10.1021/acs.oprd.6b00320
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发表时间：
2016-12-01
影响因子：
3.4
通讯作者：
Li, Zizhong
中科院分区：
文献类型：
--
作者：
Shu, Lianhe;Gu, Chen;Li, Zizhong
An efficient asymmetric synthesis of MDM2 antagonist RG7388 is reported. The highly functionalized chiral pyrrolidine carboxamide was assembled via a Cu(OAc)(2)/(R)-BINAP catalyzed asymmetric [3 + 2] cycloaddition, which gave the exo and endo adducts in a ratio of 10:1, with high enantiomeric excess for the exo isomer. A one-pot hydrolysis and retro-Mannich/Mannich isomerization of the cycloaddition adducts in the presence of aqueous sodium hydroxide afforded RG7388 in high chemical and enantiomeric purities and 69% overall yield.
