Design, synthesis, and taste evaluation of a high-intensity umami-imparting oxazole-based compound

• Published in: Bioscience, biotechnology, and biochemistry Vol. 81; no. 9; pp. 1690 - 1698
• Main Authors: Amino, Yusuke, Tahara, Yu-ki, Yamada, Kei, Nakazawa, Masakazu, Tagami, Uno, Tajima, Takaho, Kuroda, Motonaka
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 02.09.2017; Oxford University Press
• Subjects: Adult; Chemistry Techniques, Synthetic; Drug Design; Flavoring Agents - chemical synthesis; Flavoring Agents - chemistry; Flavoring Agents - pharmacology; Humans; Hydrophobic and Hydrophilic Interactions; Male; Middle Aged; Models, Molecular; Molecular Conformation; N-cinnamoyl amine; Oxazoles - chemical synthesis; Oxazoles - chemistry; Oxazoles - pharmacology; Structure-Activity Relationship; structure-optimization; Taste - drug effects; taste evaluation; time-intensity method; umami; structure-optimization; taste evaluation; cinnamoyl amine; umami; time-intensity method; N-cinnamoyl amine
• ISSN: 0916-8451; 1347-6947
• DOI: 10.1080/09168451.2017.1345613

Umami taste is imparted predominantly by monosodium glutamate (MSG) and 5′-ribonucleotides. Recently, several different classes of hydrophobic umami-imparting compounds, the structures of which are quite different from MSG, have been reported. To obtain a novel umami-imparting compound, N-cinnamoyl phenethylamine was chosen as the lead compound, and a rational structure-optimization study was conducted on the basis of the pharmacophore model of previously reported compounds. The extremely potent umami-imparting compound 2-[[[2-[(1E)-2-(1,3-benzodioxol-5-yl)ethenyl]-4-oxazolyle]methoxy]methyl]pyridine, which exhibits 27,000 times the umami taste of MSG, was found. Its terminal pyridine residue and linear structure are suggested to be responsible for its strong activity. The time taken to reach maximum taste intensity exhibited by it, as determined by the time-intensity method, is 22.0 s, whereas the maximum taste intensity of MSG occurs immediately. This distinct difference in the time-course taste profile may be due to the hydrophobicity and strong receptor affinity of the new compound. Intense umami-imparting molecule 11 was discovered by structural optimization of natural umami-imparting substance; rubenamine9 and rubescenamine 10.