1.A detailed mechanistic investigation into the reaction of 3-methylpentanoic acid with Meldrum's acid utilizing online NMR spectroscopy.
Dunn AL1,2, Codina A3, Foley DA1, Marquez BL4, Zell MT1. Magn Reson Chem. 2015 Aug 31. doi: 10.1002/mrc.4317. [Epub ahead of print]
A thorough investigation into the mechanism of the reaction of 3-methylpentanoic acid and Meldrum's acid using online NMR spectroscopy is reported. This study is an expansion of a previous analysis of this chemical transformation in the synthesis of an active pharmaceutical ingredient imagabalin. The 3-methylpentanoic acid analogue reveals similar behavior under the reaction conditions. Online NMR spectroscopy and offline characterization experiments reveal new information about the mechanism, providing conclusive spectroscopic evidence for the previously hypothesized dimer anhydride intermediate species 3-methylpentanoic anhydride as a productive intermediate. The presence of an acyl chloride intermediate species, 3-methylpentanoyl chloride, is also revealed for the first time in this synthesis. Copyright © 2015 John Wiley & Sons, Ltd.
2.Determination of 2-, 3-, 4-methylpentanoic and cyclohexanecarboxylic acids in wine: development of a selective method based on solid phase extraction and gas chromatography-negative chemical ionization mass spectrometry and its application to different wines and alcoholic beverages.
Gracia-Moreno E1, Lopez R2, Ferreira V2. J Chromatogr A. 2015 Feb 13;1381:210-8. doi: 10.1016/j.chroma.2014.12.074. Epub 2014 Dec 31.
A method to analyse 2-methylpentanoic, 3-methylpentanoic and 4-methylpentanoic acids as well as cyclohexanecarboxylic acid has been developed and applied to wine and other alcoholic beverages. Selective isolation with solid phase extraction, derivatization with 2,3,4,5,6-pentafluorobenzyl bromide at room temperature for 30 minutes, and further analysis by gas chromatography-mass spectrometry in negative chemical ionization mode provides detection limits between 0.4 and 2.4 ng/L. Good linearity up to 3.6 μg/L, satisfactory reproducibility (RSD<10%) and signal recovery of around 100% represent a robust method of analysis. Concentration data of these analytes in wine and other alcoholic beverages are reported for the first time. The levels found ranged from the method detection limits to 2630 ng/L, 2040 ng/L and 3810 ng/L for 2-, 3- and 4-methylpentanoic acids, respectively, and to 1780 ng/L for cyclohexanecarboxylic acid. There are significant differences depending on the type of wine or beverage.
3.Structures and properties of a diastereoisomeric molecular compound of (2S,3S)- and (2R,3S)-N-acetyl-2-amino-3-methylpentanoic acids.
Yajima T1, Kimura M, Nakakoji M, Horikawa T, Tokuyama Y, Shiraiwa T. Biosci Biotechnol Biochem. 2009 Oct;73(10):2293-8. Epub 2009 Oct 7.
An X-ray crystal structural analysis revealed that (2S,3S)-N-acetyl-2-amino-3-methylpentanoic acid (N-acetyl-L-isoleucine; Ac-L-Ile) and (2R,3S)-N-acetyl-2-amino-3-methylpentanoic acid (N-acetyl-D-alloisoleucine; Ac-D-aIle) formed a molecular compound containing one Ac-L-Ile molecule and one Ac-D-aIle molecule as an unsymmetrical unit. This molecular compound is packed with strong hydrogen bonds forming homogeneous chains consisting of Ac-L-Ile molecules or Ac-D-aIle molecules and weak hydrogen bonds connecting these homogeneous chains in a fashion similar to that observed for Ac-L-Ile and Ac-D-aIle. Recrystallization of an approximately 1:1 mixture of Ac-L-Ile and Ac-D-aIle from water gave an equimolar molecular compound due to its lower solubility than that of Ac-D-aIle or especially Ac-L-Ile. The results suggest that the equimolar mixture of Ac-L-Ile and Ac-D-aIle could be obtained from an Ac-L-Ile-excess mixture by recystallization from water.