Solution-phase total synthesis of the hydrophilic natural product argifin using 3,4,5-tris(octadecyloxy)benzyl tag

Tomoyasu Hirose, Takako Kasai, Takafumi Akimoto, Ayako Endo, Akihiro Sugawara, Kazuo Nagasawa, Kazuro Shiomi, Satoshi Omura, Toshiaki Sunazuka

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

A solution-phase total synthesis of argifin using 3,4,5-tris(octadecyloxy) benzyl tag as a hydrophobic protective group of carboxylic acid was developed to produce 44% overall yield for 16 linear steps. Argifin, a novel class of natural product chitinase inhibitor, is a highly water-soluble cyclic pentapeptide, so hitherto, only solid-phase synthesis techniques have been used to conveniently prepare the compound and its derivatives. 3,4,5- Tris(octadecyloxy)benzyl alcohol (HO-TAGa) and its esters are highly crystalline materials and highly capable of dissolving in less-polar solvents such as dichloromethane, benzene, THF, etc., but insoluble in polar solvents such as methanol and DMSO. The combination of HO-TAGa and Fmoc-based peptide synthesis, together with simple purification by recrystallization from MeOH solution, furnished an efficient and practical route of argifin production in the liquid-phase.

Original languageEnglish
Pages (from-to)6633-6643
Number of pages11
JournalTetrahedron
Volume67
Issue number35
DOIs
Publication statusPublished - 2011 Sep 2
Externally publishedYes

Keywords

  • Argifin
  • Chitinase inhibitor
  • HO-TAGa
  • Hydrophilic natural product
  • Hydrophobic tag
  • Solution-phase
  • Total synthesis

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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