Molecules (Oct 2021)

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

  • Takuya Kumamoto,
  • Mika Kainuma,
  • Azusa Takahashi,
  • Yoshika Matsuo,
  • Kazuaki Katakawa,
  • Takaaki Taguchi,
  • Koji Ichinose

DOI
https://doi.org/10.3390/molecules26216397
Journal volume & issue
Vol. 26, no. 21
p. 6397

Abstract

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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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