Synthesis and biological evaluation of the [d-MeAla11]-epimer of coibamide A. Issue 2 (15th January 2015)

• Record Type: Journal Article
• Authors: Nabika, Ryota; Suyama, Takashi L.; Hau, Andrew M.; Misu, Ryosuke; Ohno, Hiroaki; Ishmael, Jane E.; McPhail, Kerry L.; Oishi, Shinya; Fujii, Nobutaka
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 2(2015)
• Page Start: 302
• Page End: 306
• Publication Date: 2015-01-15
• Subjects: Hva α-hydroxyisovaleric acid -- HATU O-(7-azabenzotriazol-1-yl)-1, 1, 3, 3-tetramethyluronium hexafluorophosphate -- BTC bis(trichloromethyl) carbonate -- DIC 1, 3-diisopropylcarbodiimide -- HOBt 1-hydroxybenzotriazole -- HOAt 1-hydroxy-7-azabenzotriazole -- TFA trifluoroacetic acid -- MSNT 1-(mesitylene-2-sulfonyl)-3-nitro-1, 2, 4-triazole -- NMI N-methylimidazole -- DCM dichloromethane; Antiproliferative peptide -- Coibamide A -- Depsipeptide -- N-Methylamino acid; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2014.11.044
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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.