Asymmetric Total Synthesis of 4-Hydroxy-8- O -methyltetrangomycin, 4-Hydroxytetrangomycin, and 4-Keto-8- O -methyltetrangomycin.

Herein, we report the first asymmetric total synthesis of 4-hydroxy-8- O -methyltetrangomycin ( 1 ), 4-hydroxytetrangomycin ( 2 ), and 4-keto-8- O -methyltetrangomycin ( 3 ), angucyclinones featuring a highly oxidized nonaromatic A ring. A sequential enyne metathesis/Diels-Alder approach was utilized successfully to construct the tetracyclic skeleton of the angucyclinones. Late-stage acetonide deprotection challenges were overcome by A ring functional group manipulation, yielding a dihydroxy intermediate prior to the benzylic photo-oxidation, facilitating the total syntheses of angucyclinones 1 - 3 . The key stereocenter was established through a known Sharpless asymmetric epoxidation/regioselective epoxide opening reaction.