Jiang X,
He X,
Wong J,
Scheef S,
Hau SC.-K,
Wong TH,
Qin Y,
Fan CH,
Ma B,
Chug NL,
Huang J,
Zhao J,
Yan Y,
Xiao M,
Song X,
Hui TK. C,
Zuo Z,
Wu WK.-K,
Ko H,
Chow KH.-M,
Ng BW.-L.
*
The Chinese University of Hong Kong, P. R. of China
Lactone-to-Lactam Editing Alters the Pharmacology of Bilobalide.
JACS Au 2024;
DOI:
10.1021/jacsau.4c00416
Key words
bilobalide - molecular editing - O-to-N - lactone-to-lactam - ferroptosis - GPX4
Significance
Exploiting known skeletal rearrangements of GABA antagonist bilobalide, the authors developed an unprecedented N-to-O transformation to readily access lactam-type derivatives.
Comment
Bilobalide was reacted with amine nucleophiles to access lactam-type derivatives; these derivatives were modified further with copper-promoted coupling. Interestingly, the modified A demonstrated no GABA antagonism and atypically potent ferroptosis inhibition.
