Methyl 3-hydroxyalkanoates

Fig. 2A-F. Hydroxy acid monomers of PHAs with varied polymer backbones A standard 3-hydroxyalkanoic acid monomer B 2-methyl-3-hydroxyalkanoic acid monomer C 2,2-di-methyl-3-hydroxyalkanoic acid monomer D 4-hydroxyalkanoic acid monomer E 5-hydroxy-alkanoic acid monomer F 6-hydroxyalkanoic acid monomer. (R indicates alkyl residue or H)...

The methyl 3-hydroxyalkanoates can be transformed into optically pure compounds. Thus, the esters were hydrolyzed to the corresponding acids, and the dicyclohexyl ammonium salts were recrystallizcd from acetonitrile. Three recrystallizations gave the optically pure 3-hydroxyalka-noic acids in 50-75% yield67. In some cases, the dibenzyl ammonium salts were superior to the dicyclohexyl ammonium salts, e g., for 3-hydroxybutanoic acid, which was obtained optically pure after two recrystallizations from acetonitrile68. 

A series of methyl 3-hydroxyalkanoic acids the hydrogenation products of P-ketoesters, was saponified and the resulting acids were converted to crystallized salts. Among the various salts examined, a dibenzyl ammonium salt was found to be favorable for short chain acids (Table 10, entries 1,2,3), while a dicyclohexyl ammoniiun salt was better for long chain acids (Table 10, entries 4-... 

Aldol reactions. Reductive aldolization of methyl acrylate furnishes predominantly methyl jyn-2-methyl-3-hydroxyalkanoates in moderate yields. The catalyst system, consists of [(cod)RhCl]2, Me— DuPhos and Cl2Si(H)Me. For this reaction, significant interdependence of the metal, ligand, and hydride source for reactivity and selectivity has been witnessed. 

Figure 15.7 Cliromatographic separation of cliiral hydroxy acids from Pseudomonas aeruginosa without (a) and with (h) 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 hiomemhranes hy multidimensional gas cliromatog-raphy , pp. 191 -193, 1995, with permission from Wiley-VCH. (continuedp. 419)...

Table 1. Methyl 2-Amino-3-hydroxyalkanoates by Addition of Azaenolatcs from 2.5-Dihydro-3.6-dimeth-oxypyrazines to Saturated Aldehydes and Ketones, Followed by Hydrolysis...

By simply hydrolyzing the easily accessible 2-hydroxy-2-methylalkanenitriles with concentrated acid, 2-hydroxy-2-methylalkanoic acids are obtained without measurable racemization (Table 3). The reaction sequence from the starting ketone to the carboxylic acid can be carried out in one pot without isolation of the cyanohydrin. The enantiomeric excesses of the (/ )-cyanohydrins and the (ft)-2-hydroxyalkanoic acids are determined from the ( + )-(/T)-Mosher ester derivatives and as methyl alkanoates by capillary GC, respectively. The most efficient catalysis by (R)-oxynitrilase is observed for the reaction of hydrocyanic acid with 2-alkanoncs. 3-Alkanoncs are also substrates for (ft)-oxynitrilase, to give the corresponding (/ )-cyanohydrins32. 

An alternative to the extraction of intact PHA polymer is the isolation of PHA monomers, oligomers, or various derivatives such as esters [74]. PH As are composed of stereo-chemically pure P-3-hydroxyacids, and therefore can be used as a source of optically pure organic substrates for the chemical and pharmaceutical industry [79]. In this protocol, the defatted cake containing PHA polymer would be chemically treated to obtain the PHA derivatives. For example, transesterification of the meal with methanol would give rise to methyl esters of 3-hydroxyalkanoic acids. The PHA derivatives would then be separated from the meal with appropriate solvents. One potential disadvantage of this method is the potential alteration of the quality of the residual meal if the harsh chemical treatments required for the production of PHA derivatives lead to protein or amino acid breakdown. 

Similarly, the quinidine-catalyzed cycloaddition of ketene to 2,2-dichloro aldehydes gives -lactones of high optical purities which are easily converted to the corresponding methyl (3S)-hydroxyalkanoates (Scheme 3). °... 

A thorough study indicates that (l-methyl-4-pyridinio)boronic acid iodide is a superior catalyst for amidation under azeotropic conditions, and esterification of 2-hydroxyalkanoic acids. ... 

The enantioselective hydrogenation of methyl or ethyl 3-oxobutanoate to give methyl or ethyl 3-hydroxybutanoate is a model reaction for the preparation of 3-hydroxyalkanoic acids, ail important class of compounds which comprise key intermediates in the synthesis of natural products and in the biosynthesis and metabolism of fatty acids. 

Cao, Q. and Zhang, J. (2112) 3-hydroxyalkanoate methyl esters as Alzheimer disease dmgs. 13th International Symposium on Biopolymers ISBP2012, Cairns, Queensland (Australia). 

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). 

Chen JY, Song G, Chen CG (2006) A lower specificity of PhaC2 synthase from Pseudomonas stutzeri catalyses the production of copolyesters consisting of short-chain-length and medium-chain-length 3-hydroxyalkanoates. Antonie Van Leeuwenhoek 89 157-167 Choi J, Lee SY (1997) Process analysis and economic evaluation for poly (3-hydroxybutyrate) production by fermentation. Bioprocess Eng 17 335-342 Choi MH, Yoon SC (1994) Polyester biosynthesis characteristics of Pseudomonas citronellolis grown on various carbon sources, including 3-methyl-branched substrates. Appl Environ Microbiol 60 3245-3254... 

Zhang, X.J., Luo, R.C., Wang, Z., Deng, Y., and Chen, G.Q. (2009) Application of (i )-3-hydroxyalkanoate methyl esters derived from microbial poly-hydroxyalkanoates as novel biofuels. Biomacromolecules, 10, 707-711. 

Figure 16.8 Polyhydroxyalkanoates (PHA) can be produced from activated sludge generated from wastewater treatments. PHA-based biofuels including 3-hydroxybutyrate methyl ester (3HBME) and 3-hydroxyalkanoate methyl esters (3HAME) can also be formed from methyl-esterifying PHA. ...

Zhang XJ, Luo RC,Wang Z, DengY, Chen GQ. Applications of (R)-3-hydroxyalkanoate methyl esters derived from microbial polyhydrox kanoates as novel biofuel. Biomacromolecules 2009 10 707-11. 

A large-scale cyclization reaction of carbamates with functionalized butenoates, starting from carbamates prepared without phosgene, for the efEdent preparation of 3-(substituted phenyl)-5-isopropylidene-l,3-oxazolidine-2,4-dione derivatives (azaladones) having potent herbicidal adivity, has been described in a patent application [240]. By reacting an N-(substituted phenyl)carbamate 312 with a 2-hydroxy-3-alkenoic acid ester (for example, ethyl 2-hydroxy-3-methyl-3-butenoate) or a 3-alkoxy-2-hydroxyalkanoic add ester, at 210 °C for 15 h, azaladone 313 was formed in 71.5% yield. 

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