Practical Synthesis of MDM2 Antagonist RG7388. Part
1: A Cu(II)-Catalyzed Asymmetric [3 + 2] Cycloaddition
Lianhe Shu
Chen Gu
Dan Fishlock
Zizhong Li
10.1021/acs.oprd.6b00320.s001
https://acs.figshare.com/articles/journal_contribution/Practical_Synthesis_of_MDM2_Antagonist_RG7388_Part_1_A_Cu_II_-Catalyzed_Asymmetric_3_2_Cycloaddition/4235060
An efficient asymmetric
synthesis of MDM2 antagonist RG7388 is
reported. The highly functionalized chiral pyrrolidine carboxamide
was assembled via a CuÂ(OAc)<sub>2</sub>/(<i>R</i>)-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.
2016-10-31 00:00:00
MDM 2 antagonist RG 7388
exo isomer
one-pot hydrolysis
Practical Synthesis
enantiomeric purities
sodium hydroxide
endo adducts
cycloaddition adducts
RG 7388
BINAP
functionalized chiral pyrrolidine carboxamide
Cu