A unified and concise first asymmetric total synthesis of (−)-citreoisocoumarin (2), (−)-citreoisocoumarinol (3), 12-epi-citreoisocoumarinol (4), and (−)-mucorisocoumarins A (5) and B (6) have been accomplished from the common intermediate (−)-6-O-methyl-citreoisocoumarin (1). Central to the synthetic approach is a regioselective gold­(I)-catalyzed 6-endo-dig cyclization strategy for the construction of the isocoumarin skeleton. The other key steps in this approach included Sonogashira coupling, Tsuji-Wacker oxidation, Evans-Saksena’s 1,3-anti-reduction, and Narasaka-Prasad’s 1,3-syn-reduction. The synthetic results unambiguously confirmed the absolute configuration of the natural products mucorisocoumarins A and B as (−)-(10R,12S)-5 and (+)-(10S,12S)-6, respectively.

The synthesis of 2,6-trans-disubstituted tetrahydropyrans following the Mukaiyama type aldol reaction through C–C bond formation demonstrates the practicality of this protocol in the total synthesis of diospongin A and B.

An efficient, cost effective and protecting group tolerant CuBr2-catalyzed synthesis of 2,6-trans-disubstituted tetrahydropyran with excellent diastereoselectivity, demonstrated in the total synthesis of decytospolides A and B and their C6-epimers.