Total Synthesis of 6-Deoxydihydrokalafungin,a Key Biosynthetic Precursor of Actinorhodin,and Its Epimer |
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| Authors: | Takuya Kumamoto Mika Kainuma Azusa Takahashi Yoshika Matsuo Kazuaki Katakawa Takaaki Taguchi Koji Ichinose |
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| Affiliation: | 1.Department of Synthetic Organic Chemistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan;2.Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo 202-8585, Japan; (M.K.); (A.T.); (Y.M.); (K.K.); (K.I.);3.National Institute of Health Sciences, Kanagawa 210-9501, Japan; |
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| Abstract: | 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, epi-DDHK. Tricyclic hemiacetal with 3-siloxyethyl group was subjected to Et3SiH reduction to establish the 1,3-cis stereochemistry in the benzoisochromane, and a subsequent oxidation/deprotection sequence then afforded epi-DDHK. A bicyclic acetal was subjected to AlH3 reduction to deliver the desired 1,3-trans isomer in an approximately 3:1 ratio, which was subjected to a similar sequence to that used for the 1,3-cis isomer that successfully afforded DDHK. A semisynthetic approach from (S)-DNPA, an isolable biosynthetic precursor of ACT, was also examined to afford DDHK and its epimer, which are identical to the synthetic products. |
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| Keywords: | benzoisochromane diastereoselective reduction annulation deoxydihydrokalafungin actinorhodin |
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