Total Synthesis of 6-Deoxydihydrokalafungin, a Key Biosynthetic Precursor of Actinorhodin, and Its Epimer

In this article, we report the total synthesis of 6-deoxydihydrokalafungin (DDHK), a key biosynthetic intermediate of a dimeric benzoisochromanequinone antibiotic, actinorhodin (ACT), and its epimer, -DDHK. Tricyclic hemiacetal with 3-siloxyethyl group was subjected to Et SiH reduction to establish the 1,3- stereochemistry in the benzoisochromane, and a subsequent oxidation/deprotection sequence then afforded -DDHK. A bicyclic acetal was subjected to AlH reduction to deliver the desired 1,3- isomer in an approximately 3:1 ratio, which was subjected to a similar sequence to that used for the 1,3- isomer that successfully afforded DDHK. A semisynthetic approach from ( )-DNPA, an isolable biosynthetic precursor of ACT, was also examined to afford DDHK and its epimer, which are identical to the synthetic products.