Design of Functional Chromene-type Kobayashi Precursor: Gram-scale Total Synthesis of Natural Xanthones via Highly Regioselective Aryne Annulation.

2,2-Dimethyl-2 H -chromene motif is widely found in many bioactive molecules, and is a privileged structure in pharmaceutical area. We have developed a concise and regioselective approach to chromenes and chromanes via an aryne-based synthetic strategy. A practical, gram-scale synthetic route to chromene-type aryne precursor was explored. Subsequently, cyclization under mild conditions afforded tetracyclic xanthone skeletons with excellent regioselectivity. In addition, the resulting skeletons could be further transformed in order to construct chromenes and chromanes. Our approach provides a concise strategy for the gram-scale synthesis of chromene-type xanthones such as 6-deoxyisojacareubin, cylindroxanthone D, staudtiixanthone D, brasilixanthone A and cudracuspixanthone O.