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Synfacts 2024; 20(10): 1091
DOI: 10.1055/s-0043-1775326
Innovative Drug Discovery and Development

Late-Stage O-to-N Molecular Editing of Bilobalide Alters Pharmacology

Contributor(s):
Dirk Trauner
,
Joseph A. Flores
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;
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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.


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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.


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Publication History

Article published online:
13 September 2024

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