Hydroxy add

Two reactions for the production of L-phenylalanine that can be performed particularly well in an enzyme membrane reactor (EMR) are shown in reaction 5 and 6. The recently discovered enzyme phenylalanine dehydrogenase plays an important role. As can be seen, the reactions are coenzyme dependent and the production of L-phenylalanine is by reductive animation of phenylpyruvic add. Electrons can be transported from formic add to phenylpyruvic add so that two substrates have to be used formic add and an a-keto add phenylpyruvic add (reaction 5). Also electrons can be transported from an a-hydroxy add to form phenylpyruvic add which can be aminated so that only one substrate has to be used a-hydroxy acid phenyllactic acid (reaction 6). 

Addition of the chiral azaenolate obtained from metalation of (4A,55 )-4,5-dihydro-2-methyl-4-methoxymethyl-5-phenyloxazole (6, see Section D.1.1.1.4.3.3) to aldehydes shows lowdiastere-ofacial selectivity. Acidic hydrolysis of the aldol adducts gives 3-hydroxy adds 7 in 31 -87% yield and less than 25% ee18. 

Alcohol oxidoreductases capable of oxidizing short chain polyols are useful biocatalysts in industrial production of chiral hydroxy esters, hydroxy adds, amino adds, and alcohols [83]. In a metagenomic study without enrichment, a total of 24 positive clones were obtained and tested for their substrate specifidty. To improve the detedion frequency, enrichment was performed using glycerol or 1,2-propanediol and further 24 positive clones were deteded in this study. 

The quality of the KMn04 and CUSO4-5H2O varies with the supplier and affects the yield. Consequently, some hydroxy add, instead of the lactone, may be formed. In such a case, treatment with sodium metabisulfite solution followed by addification, converts any free acid retained on the filter cake into ladone. 

The conventional synthesis of trans-2,5-dialkyl phospholanes starting from a chiral 1,4-diol is shown in Scheme 24.1. Originally, these 1,4-diols were obtained via electrochemical Kolbe coupling of single enantiomer a-hydroxy adds [25], but this method proved to be commercially impracticable and has since been replaced by more viable biocatalytic routes [26]. Reaction of the chiral 1,4-diol with thionyl chloride followed by ruthenium-catalyzed oxidation with so-... 

K. Yonaha u. K. Soda, Ad v. Biochem. Eng./Biotcchnol. 33,95 -130 (1986) . .Applications of Stereoselectivity of Enzymes Synthesis of Optically Active Amino Acids and a-Hydroxy Adds and Stereospecific Isotope Labeling of Amino Acids, Amines, and Coenzymes". 

Alpha oxidation and omega oxidation. Animal tissues degrade such straight-chain fatty acids as palmitic acid, stearic acid, and oleic acid almost entirely by (3 oxidation, but plant cells often oxidize fatty acids one carbon at a time. The initial attack may involve hydroxylation on the a-carbon atom (Eq. 17-3) to form either the d- or the L-2-hydroxy add.17 18-32 323 The L-hydroxy acids are oxidized rapidly, perhaps by dehydrogenation to the oxo acids (Eq. 17-3, step b) and oxidative decarboxylation, possibly utilizing H202 (see Eq. 15-36). The D-hydroxy acids tend to accumulate... 

From the beginning of the 1960s, the progress in depsipeptide chemistry was connected with the utilization and further development of the mixed anhydride approach for the initial formation of the ester link between a suitably N-protected amino acid and the hydroxy acid ester. The reagent predominantly applied for the construction of the depsipeptide unit was benzenesulfonyl chloride in pyridine. This reagent, introduced by Shemyakin and co-workers in depsipeptide chemistry, was shown to be an efficient reagent for the formation of the ester bond between a protected amino acid and the hydroxy add component (Scheme 4).[21 22 ... 

IV-Benzyloxycarbonyl-Substituted Aminoacyl Hydroxy Add ferf-Butyl Esters General Procedure for the Synthesis of Protected Didepsipeptides Using Benzenesulfonyl Chloride 135 ... 

Synthesis of Boc-Aminoacyl Hydroxy Add Benzyl Esters Typical Procedure 1631... 

To a soln of /V-Boc-protected-amino acid (Boc-Ala-OH, Boc-D-Val-OH, or Boc-Aib-OH, 1 mmol), an a-hydroxy add benzyl ester (H-L-Lac-OBzl, or H-i.-Hyv-OBzl, 1 mmol) and 4-(dialkylamino)pyridine (DMAP or Ppyr, 1 mmol) in CH.Ch (15 mL), a soln of DCC (1.1 mmol) in CH.Ch (5 mL) was added. The mixture was stirred at 25 °C and followed by TLC (silica gel, CHC13 or hexane/EtOAc 4 1). The iV V -dicyclohexylurea was filtered off and the filtrate concentrated to dryness. The residue was dissolved in EtOAc, cooled and the /V,/V -dicyclohexylurea was removed by filtration. The filtrate was washed with 1M aq KHS04, H20, 5% aq NaHC03, dried (MgS04), and concentrated to dryness in vacuo. The resulting oil was washed with petroleum ether and dried in vacuo to afford the analytically pure dep-sipeptide in 90-98% yield. The purity of the products was confirmed by TLC quantitative analysis IR and NMR spectra. 

Scheme 8 3-Oxo Ester Route to a-Amino-p-hydroxy Adds...

Hydrogenation of f)-oxo esters by BINAP-ruthenium(II) complexes produces the corresponding y-amino- 3-hydroxy adds with very high stereoselectivity)44 461 For example, hydrogenation of the AT-Boc derivative 31 (R1 = iBu R2 = Et X = Boc Y = H) in the presence of RuBr2[(R)-BINAP] leads to (35,4R)-Boc-statine almost exclusively and in quantitative yield (Table 4, entry g))44 ... 

A major method for the preparation of y-amino-()-hydroxy adds of syn configuration is the stereocontrolled reduction of enantiomerically pure tetramic acids 32, followed by alkaline or acid hydrolysis of the resulting N-protected 4-hydroxy lactams 33 (Scheme 9))53-571... 

Formation of the rigid, bicyclic lactams 58-60 facilitates the determination of the relative configurations at the C3 positions in the case of a-monosubstituted y-amino (1-hydroxy adds by H NMR spectroscopy116-62f<2l (Scheme 24). The cisltram stereochemistry of the lactam derived from the a,a-difluoride derivative cannot be assigned on the basis of the /4>5 coupling constant in this case, 13C NMR spectra1151 or NOE effects 78 are more informative. The signal from the C5 atom of the ds-isomer appears upfield relative to that of the /ram-isomer. 

The explanation advanced by the above authors far the relative inertness of (XL) with respect to (XXXIX) involves electron depletion by non-classical resonance. The conformation allowing such resonance is one of high energy in the case of the hydroxy add (XXXTX). but jg forcibly present in laotone (XL) by virtue of its bridged structure, Th non-classical structure envisaged by Woodward and oo-worker 18,s appears to be of the type (XLI). 

The IR spectra of hydroxy adds are not very different from the spectra of the corresponding carboxylic acids. The additional hydroxyl groups usually produce minor displacements of the carbonyl vibrational bands to higher energies and, of course, contribute additional characteristic... 

The interpretation of the IR spectra of hydroxy adds in the range 1500-1000cm-1 is rather difficult.54,59 In this region, absorptions corresponding to carbon-hydrogen deformations (CH3, CH2, CH groups) can be observed, as well as C—O stretching vibrations and in-plane deformations... 

These variations in reactivity are usually not large enough to be of practical importance. The behavior of ethers of hydroxy adds, some of which rearrange at temperatures not far above 100°, has been discussed (P- U). 

Periodic acid and lead tetraacetate react similarly with simple a-glycols, and the rate of oxidation by each reagent is more rapid for cia-than for trans-glycols. The two oxidants, however, manifest a marked difference in their action upon a-hydroxy acids and upon oxalic acid. Lead tetraacetate readily oxidizes a-hydroxy adds, as well as oxalic add, at room temperature. Periodic add, on the other hand, does not react with oxalic acid and oxidizes a-hydroxy acids only slowly even at... 

For much of the last century, scientists attempted to make useful plastics from hydroxy adds such as glycolic and lactic acids. Poly(glycolic acid) was first prepared in 1954, but was not commercially developed because of its poor thermal stability and ease of hydrolysis. It did not seem like a useful polymer. Approximately 20 years later it found use in medicine as the first synthetic suture material, useful because of its tendency to undergo hydrolysis. After the suture has served its function, the polymer biodegrades and the products are assimilated (Li and Vert 1995). Since then, suture materials, prosthetics, artificial skin, dental implants, and other surgical devices made from polymers and copolymers of hydroxy carboxylic acids have been commercialized (Edlund and Albertsson 2002). 

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