Scalable solution-phase synthesis of the biologically active cyclodepsipeptide destruxin E, a potent negative regulator of osteoclast morphology

Masahito Yoshida, Hiroshi Sato, Yoshitaka Ishida, Hiroshi Nakagawa, Takayuki Doi

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

The scalable solution-phase synthesis of the cyclodepsipeptide destruxin E (1) has been achieved. Diastereoselective dihydroxylation of the terminal alkene in a 2-alkoxy-4-pentenoic amide, 7, was successfully accomplished utilizing (DHQD)2PHAL as the chiral ligand, and it was found that the use of the l-proline moiety in the substrate as a chiral auxiliary was essential for the induction of high diastereoselectivity to afford the key compound 4 on a gram scale. MNBA-mediated macrolactonization of 3 was also performed without formation of the dimerized product even under higher-dilution conditions, and it is noteworthy that the internal hydrogen bonds and s-cis configuration of the amide bond between N-methylalanine and N-methylvaline in the cyclization precursor 3 would assist in the macrolactonization to provide the macrolactone 2 without forming a dimerized product. Finally, epoxide formation in the side chain afforded destruxin E (1) on a gram scale in high purity (>98%).

Original languageEnglish
Pages (from-to)296-306
Number of pages11
JournalJournal of Organic Chemistry
Volume79
Issue number1
DOIs
Publication statusPublished - 2014 Jan 3

ASJC Scopus subject areas

  • Organic Chemistry

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