Synthesis of a biphenylalanine analogue of apratoxin a displaying substantially enhanced cytotoxicity

Yuichi Onda, Kazuki Fukushi, Kosuke Ohsawa, Masahito Yoshida, Yuichi Masuda, Takayuki Doi

Research output: Contribution to journalArticlepeer-review

Abstract

The concise synthesis of the 3,7-dihydroxy-2,5,8,8-tetramethylnonanoic acid moiety of apratoxin A and the total synthesis of compound 3, a 4-biphenylalanine (Bph) analogue of apratoxin A, have been demonstrated. The Bph analogue 3 exhibited a 16-fold increase in cytotoxicity against HCT-116 cells with respect to apratoxin A. This evidence indicated that existing the 4-phenyl group of Bph in 3 significantly enhanced its cytotoxicity, a conclusion corroborated by the 100-fold difference in cytotoxicity against HCT-116 cells observed between apratoxin M7 and apratoxin M16, which is characterized by the presence of a 4-phenyl group where apratoxin M7 displays a 4-methoxy group. Results from a conformational study using a distance geometry method suggested that 3 and apratoxin A adopt similar conformations in CD3CN.

Original languageEnglish
Pages (from-to)679-691
Number of pages13
JournalHeterocycles
Volume101
Issue number2
DOIs
Publication statusPublished - 2020 Jan 1

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmacology
  • Organic Chemistry

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