Concise syntheses of GB22, GB13, and himgaline by cross-coupling and complete reduction

Neuroactive metabolites from the bark of Galbulimima belgraveana occur in variable distributions among trees and are not easily accessible through chemical synthesis because of elaborate bond networks and dense stereochemistry. Previous syntheses of complex congeners such as himgaline have relied on iterative, stepwise installation of multiple methine stereocenters. We decreased the synthetic burden of himgaline chemical space to nearly one-third of the prior best (7 to 9 versus 19 to 31 steps) by cross-coupling high fraction aromatic building blocks (high F(sp)2) followed by complete, stereoselective reduction to high fraction sp(3) products (high F(sp)3). This short entry into Galbulimima alkaloid space should facilitate extensive chemical exploration and biological interrogation.

Automated summary

Neuroactive metabolites from the bark of Galbulimima belgraveana exhibit varying distributions among trees and are challenging to access through chemical synthesis due to intricate bond networks and dense stereochemistry. However, a new synthetic approach has been developed to reduce the synthetic burden and increase efficiency, allowing for further chemical exploration and biological investigation in Galbulimima alkaloid space.