Total synthesis and conformational analysis of apratoxin C

Yuichi Masuda, Jun Suzuki, Yuichi Onda, Yuta Fujino, Masahito Yoshida, Takayuki Doi

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Total synthesis of apratoxin C, a cyanobacterial cyclodepsipeptide with highly potent cytotoxicity against some cancer cell lines, was achieved using the apratoxin A synthetic strategy developed by us. To elucidate the relationship between conformation and activity, the tertiary structure of apratoxin C was analyzed by NMR spectroscopy. We obtained 37 ROEs and five 3JH,H values, which were translated into distance and dihedral angle constraints, respectively. Molecular modeling was performed with a restrained conformational search by a distance geometry method. The lowest energy structure indicated that the methyl group at C37 and the isopropyl group at C39 play critical roles in maintaining the conformation, whereas the methyl group at C34 does not. Moreover, we confirmed that apratoxin A and C possess similar conformations, providing a likely explanation for their nearly equivalent cytotoxicities.

Original languageEnglish
Pages (from-to)8000-8009
Number of pages10
JournalJournal of Organic Chemistry
Volume79
Issue number17
DOIs
Publication statusPublished - 2014 Sep 5

ASJC Scopus subject areas

  • Organic Chemistry

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