Synthesis and molecular structure of piplartine (=piperlongumine)

The structure of piplartine (=piperlongumine) was established as ($\text{1}$)-$\text{3}$-3',4',5'-trimethoxycinnamoyl-5,6-dihydro-2(1H)-pyridone ($\text{13}$) by synthesis and by an X-ray crystallographic analysis. Model condensation of ($\text{E}$)-3,4,5-trimethoxycinnamoyl chloride and crotonamide gave not the expected cinnamoylcrotonamide, but ($\text{1}$)-$\text{N}$-3', 4', 5' -trimethoxycinnamoyl-3-chlorobutyramide ($\text{12}$).