Synthesis and biological evaluation of the [d-MeAla(11)]-epimer of coibamide A

  • Bioorg Med Chem Lett. 2015 Jan 15;25(2):302-6. doi: 10.1016/j.bmcl.2014.11.044.
Ryota Nabika  1 ,  Takashi L Suyama  2 ,  Andrew M Hau  2 ,  Ryosuke Misu  1 ,  Hiroaki Ohno  1 ,  Jane E Ishmael  2 ,  Kerry L McPhail  2 ,  Shinya Oishi  3 ,  Nobutaka Fujii  4
Affiliations
  • 1. Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
  • 2. Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR 97331, USA.
  • 3. Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address: [email protected].
  • 4. Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address: [email protected].
PMID: 25488840 DOI: 10.1016/j.bmcl.2014.11.044
Abstract

Coibamide A is a highly potent antiproliferative cyclic depsipeptide, which was originally isolated from a Panamanian marine cyanobacterium. In this study, the synthesis of coibamide A has been investigated using Fmoc-based solid-phase peptide synthesis followed by the cleavage of the resulting linear peptide from the resin and its subsequent macrolactonization. The peptide sequence of the linear coibamide A precursor was constructed on a solid-support following the optimization of the coupling conditions, where numerous coupling agents were evaluated. The macrocyclization of the resulting linear peptide provided the [d-MeAla(11)]-epimer of coibamide A, which exhibited nanomolar cytotoxic activity towards a number of human Cancer cell lines.

Keywords
Antiproliferative peptide; Coibamide A; Depsipeptide; N-Methylamino acid.