Biomimetic Intramolecular Diels-Alder Reaction to Construct the Tetrahydroindane Core of Elansolid A1/A2

Abstract

The Elansolid A1/A2 is metabolite from the gliding bacterium Chitinophaga sanctii and shows antibiotic activity against Gram-positive bacteria. Up to now, the total synthesis of this natural product has not been reported yet due to its structure complexity, which arises from the trans-tetrahydroindane unit and (Z)-(E)-(Z) triene motif as well as a 19-member macrolactone. In this study, two new O-functionalized substrates were synthesized to undergo the biomimetic intramolecular Diels-Alder reactions (IMDA) catalyzed by a chiral phosphoric acid to build the key trans-tetrahydroindane core of Elansolid A1/A2 via a vinylic p-quinone methide intermediate. This result shows that an improved dr (1.8∶1) of IMDA reaction and shorter synthetic steps could be achieved.