Asymmetric Total Synthesis of Chaetoglobin A

An asymmetric total synthesis of chaetoglobin A was achieved.Atroposelectiveoxidative coupling of a phenol incorporating all but one carbon ofthe final product was used as a key step to generate axial chirality.The stereochemical outcome of the catalytic oxidative phenolic withthe highly substituted phenol used herein was found to be oppositethat of the simpler congeners reported previously, providing a cautionarytale about extrapolating asymmetric processes from simple to morecomplex substrates. Optimization of the postphenolic coupling stepsincluding formylation, oxidative dearomatization, and selective deprotectionsteps are outlined. The tertiary acetates of chaetoglobin A were exceptionallylabile due to activation by the adjacent keto groups, which complicatedeach of these steps. In contrast, the final oxygen to nitrogen exchangeproceeded readily and the spectroscopic data from the synthetic materialmatches that of the isolated natural product in all respects.

Automated summary

An asymmetric total synthesis of chaetoglobin A was accomplished by utilizing atroposelective oxidative coupling reaction of a phenol. The stereochemistry of the catalytic oxidative phenolic reaction was found to be opposite to that of the simpler congeners, illustrating the caution needed when extrapolating asymmetric reactions to complex substrates. The optimization of postphenolic coupling steps and difficulties caused by the lability of tertiary acetates in chaetoglobin A were discussed, while the final oxygen to nitrogen exchange proceeded smoothly and the spectroscopic data of the synthetic material matched the natural product.