2-Methylbutanoic acid enantiomers

From the analytical point of view, it is worth noting the biogenetic pathway of 2-methylbutanoic acid starting from isoleucine [(2S)-amino-(3S)-methylpenta-noic acid]. The (S)-configuration of the precursor is expected to remain but also enzymatic racemisation (by enolisation of the intermediate 2-oxo-3-meth-ylpentanoic acid) is known from the literature. It is not surprising that in some cases 2-methylbutanoic acid is detected as an enantiomeric ratio more or less different from the expected homochiral S enantiomer (Table 17.2) [35-40]. 

Of course, during processing of fruit juices hydrolysis effects may occur, leading to decreased amounts of ethyl 2-methylbutanoate. However, its enantiomeric purity remains unchanged, whilst the corresponding 2-methylbutanoic acid is found as the (S)-enantiomer (99.5% or more) [33-37]. Consequently, the detection of racemic 2-methybutanoic acid (or the corresponding esters) definitely proves the addition of a synthetic (so called nature-identical) flavour compound. 

Figure 10.10 The synthesis of 2R-methylbutanoic acid, illustrating the use of a chiral auxiliary. The chiral auxiliary is 2S-hydroxymethyltetrahydropyrrole, which is readily prepared from the naturally occurring amino acid proline. The chiral auxiliary is reacted with propanoic acid anhydride to form the corresponding amide. Treatment of the amide with lithium diisopropyla-mide (LDA) forms the corresponding enolate (I). The reaction almost exclusively forms the Z-isomer of the enolate, in which the OLi units are well separated and possibly have the configuration shown. The approach of the ethyl iodide is sterically hindered from the top (by the OLi units or Hs) and so alkylation from the lower side of the molecule is preferred. Electrophilic addition to the appropriate enolate is a widely used method for producing the enantiomers of a-alkyl substituted carboxylic acids...

Alkylcarbonic acids have been separated into their enantiomers without any deriva-tization and their sequence of elution was assigned by co-injection with enantio pure references [17]. Latest results on stereoselective flavour evaluation revealed characteristic sensory properties for all the enantiomers of 2-alkylbranched acids, esters and corresponding alcohols. Tremendous differences between the mirror images of 2-methylbutanoic acid have been found. While the R-enantiomer exhibits a penetrating, cheesy-sweaty odour, the S-enantiomer emits a pleasant sweet and fine fruity note [87, 88]. All commercially available homologues of 2-methylbutanoic acid esters and 2-methylbutyl acetate are simultaneously stereoanalyzed, using heptakis (2,3-di-O-methyl-6-0-tert-butyldimethylsilyl)-P-cyclodextrin (DIME-P-CD) in PS 268 as the chiral stationary phase [88] (Eig. 6.33, Table 6.19). 

A chiral 2-alkyl-4,5-dihydrooxazole 7 is obtained by the use of (+)-( 5, 2 S)-1-phenyl-2-aminopropane-1,3-diol, available from the chiral pool (see p 115). From this, the methyl ether 8 is prepared using sodium hydride and iodomethane. As a result of internal asymmetric induction, the alkylation of its lithium derivative occurs diastereoselectively. In the case of = Me, = Et, hydrolysis yields the (+)-( S)-enantiomer of 2-methylbutanoic acid 9, with ee = 67 %, as the main product ... 

Fig. 12 Enantioselective sensing by conformational changes in the sensors, (a) Mechanism of sensing in fluorophore-bearing cyclodextrins by interaction with a guest (b) water soluble imidazolium containing BINOL macrocycles 38, 39 (c) tris- and bis(oxazolmyl)phtaiols (40, 41) (d) l,8-bis(9,9 -diacridyl)naphthalene derivative 42 (e) Stem-Vobner plot of 42 upon interaction with enantiomers of a-halo acids (left 2-chloropropanoic acid, right 2-bromo-3-methylbutanoic acid), showing nonlinear response (from [85] reproduced by permission of The Royal Society of Chemistry)...

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