Hydroxyalkanoic acids, chiral

Figure 15.7 Chromatographic separation of chiral hydroxy acids from Pseudomonas aeruginosa without (a) and with (b) co-injection of racemic standards. Peak identification is as follows 1, 3-hydroxy decanoic acid, methyl ester 2, 3-hydroxy dodecanoic acid, methyl ester 3, 2-hydroxy dodecanoic acid, methyl ester. Adapted from Journal of High Resolution Chromatography, 18, A. Kaunzinger et al., Stereo differentiation and simultaneous analysis of 2- and 3-hydroxyalkanoic acids from biomembranes by multidimensional gas chromatography ,pp. 191-193, 1995, with permission from Wiley-VCH. (continuedp. 419)...

Many hydroxycarboxylic acids are naturally occurring, and their coordination chemistry is of importance in biological processes. These complexes also have uses in many other areas such as analytical chemistry, electroplating processes, and pharmacology. The most widely studied ahphatic hydroxy acids are the lower members of the 2-hydroxyalkanoic acids, while studies of aromatic hydroxy acids have often centered on salicylic acid. A number of these acids contain one or more chiral carbon centers, and hence complexes of these acids have been useful in studying chiroptical properties such as the Cotton Effect see Cotton Effect). 

Ren, Q., Grubelnik, A., Ruth, K., Hoerler, M., Hartmann, R., Felber, H. Bacterial poly(hydroxyalkanoates) as a source of chiral hydroxyalkanoic acids. Biomacromol 6, 2290-2298 (2005)... 

Various enantiomerically pure (/ )-3-hydroxyalkanoic acids (RHA) can be conveniently prepared by depolymerizing the biosynthesized PHA. De Roo et al. (2002) produced the chiral RHA and RHA methyl esters via hydrolytic degradation of PHA synthesized by pseudomonads. They first hydrolyzed the recovered PHA by acid methanolysis and then distilled the RHA methyl ester mixture into several fractions. Subsequently, the RHA methyl esters were saponified to yield the corresponding RHA with final yields of the RHA up to 92.8% (w/w). 

Chiral R-form hydroxyalkanoic acids are normally difficult to synthesize by chemical means. The occurrence of over 120 different chiral R-forms of PHA monomers reflects the low substrate specificity of PHA synthases, which are the key enzymes of PHA biosynthesis [7, 8, 22], These can be used as a rich pool of chrial compounds [13]. In addition, the importance of bacterial anabolism and catabolism, which provide the coenzyme A thioesters of the respective monomers as substrates to these PHA synthases, is also important in controlling the structure of hydroxyalkanoic acids [23]. 

Because PHAs are polymers composed of chiral building blocks, hydrolysis of PHAs leads to the release of the chiral monomers, which are valuable starting material for the synthesis of pharmaceuticals and specialty chemicals. An efficient method has been reported for the production of enantiomerically pure (R)-(-)-hydroxyalkanoic acids by in vivo depolymerization of PHAs (Lee et al. 1999c). Those (R)-(-)-3-hydroxyalkanoic acids of 4—12 carbon atoms and (R)-(-)-3-hydroxy-5-phenylvaleric acid were prepared by providing the environmental condition under which cells possess a high activity of intracellular PHA depolymerase and a low activity of a key enzyme that could convert the chiral monomer into another compound. Monomer (R)-(-)-3-hydroxybutyric acid could be produced at a high yield in 30 min by in vivo depolymerization of poly(3HB) accumulated in Alcaligenes latus. 

An excellent source of readily available chiral auxiliaries is to be found in amino-acids, and Schollkopf and co-workers have once again used them to prepare lithiated dihydropyrazines (11). In particular, they have used L-valine, tert-leucine, and (5)-0,0-dimethyl-a-methyldopa in the synthesis of (i )-a-amino-acids from, for example, glycine. "" The same authors have also used the oxazinones (12) to give chiral (S )-a-alkyl-a-phenylglycines from DL-phenyl-glycines however, in this case 2-hydroxyalkanoic acids are used as the chiral auxiliaries. In a quite different approach, protected and lithiated glycine is converted into alanine by the methyl sulphate (13) in enantiomeric excesses approaching 40... 

In the case of 5C/-PHAs, the monomers consist of three to five carbon atoms, and mainly constitute R-configured chiral 3-hydroxyalkanoates. jcZ-PHAs mainly feature properties of classical thermoplasts hence, on the market, they compete with poly(ethylene) (PE) or poly(propylene) (PP), and, to a certain extent, also with bio-based poly(Z,-lactic acid). The strain Cupriavidus necator, a member of the Burkholderiaceae family, can be regarded as the best investigated bacterial jcZ-PHA producer. 

Another way of generating biopolymers is the fermentation of starch, sugar and other commodities by various microorganisms. Typical examples are poly(hydroxyalkanoates) (especially poly(hydroxybuty-rate) (PHB)) and poly(lactic acid) (PLA). Due to the chirality of lactic acid (D- L-form), two distinct forms of poly(lactic acid) exist (poly(L-lactic acid) and poly(D-lactic acid)). PLA is used, e.g. in biomedical application (sutures, stents, drug-delivery, preparation of bioplastic), in agriculture (mulch-film), packaging, and in blends with synthetic polymers. 

---