Ryffel DB,
Ryffel PC,
Martinelli M,
Pillai VR,
Sarlah D *.
Rice University, Houston and University of Illinois at Urbana–Champaign, USA
Stereoselective Total Synthesis of Nimbolide.
J. Am. Chem. Soc. 2025;
147: 14083-14087
DOI:
10.1021/jacs.5c04899
Keywords
(+)-nimbolide - limonoids - Pd-catalyzed borylative Heck cyclization - Pd-catalyzed
enolate cross-coupling - stereoretentive etherification - radical cyclization - lactonization
Significance
Sarlah and co-workers report the convergent total synthesis of ( + )-nimbolide in
11 steps (longest linear sequence). This natural product has shown promising biological
activities regarding the reduction of certain cancer hallmarks, such as cancer metastasis,
cancer-related inflammation and angiogenesis.
Comment
The authors developed a borylative Heck cyclization to access trans-decalin scaffold C, using a carvone-derived precursor A. Further adjustments of the oxygenation pattern furnished building block J. Epoxidation followed by stereoretentive ring-opening by alcohol K furnished ether L. Final radical cyclization and lactonization gave the natural product ( + )-nimbolide.
