Submitted to: Synthetic Communications
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 14, 2011
Publication Date: May 1, 2013
Repository URL: http://handle.nal.usda.gov/10113/56934
Citation: Zeller, W.E. 2013. Synthesis of (+)- and (-)-phaselic acid. Synthetic Communications. 43(10):1345-1350. Interpretive Summary: Phaselic acid is a common plant substance thought to be involved in plant stress responses. Our interest in this substance stems from previous studies showing that the presence of phaselic acid in red clover is crucial to the preservation of protein in this forage during the ensiling process. In order to conduct more studies on the role of phaselic acid and similar substances in silage preservation, we required reasonable quantities of it. However, phaselic acid is not commercially available and is usually obtained in small quantities through isolation from plant material. Therefore, we developed a laboratory synthesis of phaselic acid. The synthesis described here should be applicable to other scientists needing reasonable quantities of phaselic acid and similar substances.
Technical Abstract: (2S)-Phaselic acid (2S-O-caffeoylmalate) is a common plant metabolite belonging to the o-diphenol subclass of phenolic secondary metabolites. Our interest in this metabolite stems from previous studies showing that the presence of (2S)-phaselic acid in red clover is crucial to the preservation of utilizable protein in this forage during the ensiling process. We required reasonable quantities of (2S)-phaselic acid, both as a reference standard and for a variety of studies directed at elucidating the biological pathway of specific secondary phenolic metabolites. The synthesis of both enantiomers of phaselic acid (2-O-caffeoylmalate) is described. The previously unreported acetate-protected caffeic acid anhydride, prepared through triphosgene-mediated coupling of caffeic acid diacetate, was used with appropriately protected malic acid derivatives as coupling partners to provide fully protected phaselic acid. Sequential unmasking of the protecting groups afforded phaselic acid in an acceptable overall yield. The synthetic sequence described here should be applicable to preparation of additional members of this important class of secondary metabolites.