Synthetic Studies Toward 2-Epi Altemicidin and Its Derivatives: Construction of the 6-Azatetrahydroindane Core.

Isoleucyl-tRNA synthetase (IleRS) inhibitors are promising drug targets. SB-203207, an altemicidin-type monoterpene alkaloid, potently inhibits IleRS. To elucidate the stereochemical structure-activity relationship of SB-203207, we investigated the synthesis of 2-epi altemicidin. We achieved the stereoselective construction of the 6-azatetrahydroindane core of 2-epi altemicidin and its derivatives, featuring a nitrogen-containing quaternary setereogenic center. We also improved access to the previously reported intermediate, shortening the sequence by three steps.