Synthesis of and tautomerism in 3-acyltetramic acids.

Journal article

The synthesis of 3-acyltetramic acids, the substructure of bioactive natural products, via O-acylation of tetramic acids with carboxylic acids followed by acyl migration, has been investigated. This acylation sequence is mediated by N,N'-dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP) and is very sensitive to the nature of the nitrogen substituent (R(1)), the nature of the carboxylic acid (R(2)CO(2)H), and the amount of DMAP. Acylation of N-acyl tetramic acids with an alkyl carboxylic acid using 1.3 equiv of DMAP (with 1.1 equiv of DCC) unexpectedly gave the 3-acyltetramic acid directly as a result of acyl migration induced by excess amounts of DMAP. On the other hand, N-unsubstituted, N-alkyl, and N-acyl tetramic acids with alkyl and aromatic carboxylic acids gave the O-acyl tetramic acids by using only 0.1 equiv of DMAP (with 1.1 equiv of DCC); these could be further rearranged to the acyl product by treatment with excess DMAP. The tautomeric equilibrium of these 3-acyltetramic acids in solution was found to strongly depend on the nitrogen substituent group (R(1)) rather than the 3-acyl group.

Authors: Jeong, Y; Moloney, M

• Publication status: Published
• Journal: Journal of organic chemistry
• Volume: 76
• Issue: 5
• Pages: 1342-1354
• Publication date: 2011-03-01
• DOI: 10.1021/jo102304y
• EISSN: 1520-6904
• ISSN: 0022-3263
• Language: English
• Keywords: Stereoisomerism; Molecular Structure; Tenuazonic Acid; Biological Factors