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

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.

SUBMITTER: Kumamoto T

PROVIDER: S-EPMC8587838 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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

Kumamoto Takuya T Kainuma Mika M Takahashi Azusa A Matsuo Yoshika Y Katakawa Kazuaki K Taguchi Takaaki T Ichinose Koji K

Molecules (Basel, Switzerland) 20211022 21

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 AlH< ...[more]

PMID: 34770806

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