SUBJECTS mandelic acid

Toniolo reported the carbonylation of aromatic aldehydes containing electron-donating substituents with a Pd/PPh3 catalyst system in the presence of HC1 to give phenylacetic acid derivatives [64]. No activity was observed in the absence of PPI13 or HC1, and high yields could be achieved with alkanols as solvent (e.g., EtOH). It is believed that the mechanism involves HC1 addition to the aldehyde, with the resultant chlorohydrin being subject to oxidative addition to Pd, CO insertion, and alcoholysis. Upon Cl -o- OR substitution with the formed mandelic acid derivative, a second carbonylation takes place,... 

To elucidate the metabolic pathway of phenylmalonic acid, the incubation broth of A. bronchisepticus on phenylmalonic acid was examined at the early stage of cultivation. After a one-day incubation period, phenylmalonic acid was recovered in 80% yield. It is worthy of note that the supposed intermediate, mandelic acid, was obtained in 1.4% yield, as shown in Eq. (8). The absolute configuration of this oxidation product was revealed to be S. After 2 days, no metabolite was recovered from the broth. It is highly probable that the intermediary mandelic acid is further oxidized via benzoylformic acid. As the isolated mandelic acid is optically active, the enzyme responsible for the oxidation of the acid is assumed to be S-specific. If this assumption is correct, the enzyme should leave the intact l -enantiomer behind when a racemic mixture of mandelic acid is subjected to the reaction. This expectation was nicely realized by adding the racemate of mandelic acid to a suspension of A. bronchisepticus after a 4-day incubation [4]. 

Following an initial resolution step with 0.5 mol equivalents (R)-mandelic acid in TBME, the crystalline product was filtered and tlie waste isomers in the mother liquors (39% ee) were washed with base and then subjected to racemization with the SCRAM catalyst. Upon completion, the catalyst precipitated and was screened, fresh racemic amine was added, and the whole was resolved a second time. The process was repeated several times, giving the results summarized in Table 13.2. 

Subject Phenylacetic Acid Mandelic Acid o-Hydroxy- phenylacetic Acid Phenyllactic Acid Phenyl- pyruvic Acid p-Hydroxy- phenylacetic Acid... 

Independent synthesis of the crystalline amide LXVII established its identity and its configurational relationship to L-(+)-mandelic acid. The latter acid was converted to ethyl L-(+)-mandelate (LXVIII), and the ether linkage introduced by reaction with ethyl bromoacetate in the presence of silver carbonate, under conditions such that Walden inversion was impossible. The resulting ethyl D-(+)-2-phenyldiglycolate (LXVI), was subjected to ammonolysis, giving a crystalline product, m. p. 174-174.5°, [a]26D 106.2°. This showed no mixed melting point depression and an identical infrared absorption spectrum with the sample of LXVII obtained from /3-D-xylopyranosylbenzene. The enantiomorphic l-(—)-2-phenyldiglycolamide was also prepared by identical synthetic steps from d-( —)-mandelic acid. 

Hydrogenation. The double bond of cinnamic acid derivatives is saturated by subjecting it to PdCl2 in HCOOH in an alkaline medium. This transfer hydrogenation also reduces benzoylformic acid to mandelic acid in 80% yield. 

The oral toxicity in animals was found to be low to very low. An LD50 value of 3500 mg/kg for rats has been documented (NIOSH 1986). No adverse effects were noted in animals subjected to chronic inhalation exposure at below 400 ppm. At higher dosages only the liver was affected (ACGIH 1986). Ethyl benzene is eliminated from the body by metabolic excretion. The urinary metabolites in humans are mainly mandelic acid, C6HsCH(OH)COOH, and benzoyl-formic acid, CeHsCOCOOH. 

The kinetics of oxidation of substituted mandelic acids (a-hydroxyphenylacetic acid) in sulfate and mixed perchlorate/sulfate solutions are the subject of the four reports from Calvaruso et al. (1981a, b) and Arcoleo et al. (1977,1979). The oxidation reaction yields (substituted) benzaldehydes upon decarboxylation of mandelic acid. The oxidation of the p-nitro and p-methoxy derivatives in sulfuric acid proceeds without significant complex formation. The authors conclude that the reaction proceeds through two reactive Ce(IV) species,... 

A large number of studies have been carried out on this subject in connection with the production of plastics. As mentioned earlier benzoic acid, mandelic acid, phenylglycol and phenyl glyoxylic acid are formed [195, 197] (Fig. 8). 

As shown in Scheme 9, various organic compounds can act as a chiral initiator of asymmetric auto catalysis. 2-Methylpyrimidine-5-carbaldehyde 9 was subjected to the addition of z-Pr2Zn in the presence of chiral butan-2-ol, methyl mandelate and a carboxylic acid [74], When the chiral alcohol, (S)-butan-2-ol with ca. 0.1% ee was used as a chiral initiator of asymmetric autocatalysis, (S)-pyrimidyl alkanol 10 with 73% ee was obtained. In contrast, (,R)-butan-2-ol with 0.1% ee induced the production of (A)-10 with 76% ee. In the same manner, methyl mandelate (ca. 0.05% ee) and a chiral carboxylic acid (ca. 0.1% ee) can act as a chiral initiator of asymmetric autocatalysis, therefore the S- and IC enantiomers of methyl mandelate and carboxylic acid induce the formation of (R)- and (S)-alkanol 10, respectively. Chiral propylene oxide (2% ee) and styrene oxide (2% ee) also induce the imbalance of ee in initially forming the zinc alkoxide of the pyrimidyl alkanol in the addition reaction of z-Pr2Zn to pyrimidine-5-carbaldehyde 11 [75]. Further consecutive reactions enable the amplification of ee to produce the highly enantiomerically enriched alkanol 12 (up to 96% ee) with the corresponding... 

Deracemization of mandelic add with the combined action of two enzymes has been reported. rac-MandeUc acid is acylated by a Pseudomonas sp. lipase in diisopropyl ether. After solvent removal the mfacture of mandeUc acid enriched in the R-form and the 0-acetyl derivative of the S-configuration are subjected to the mandelate racemase-catalyzed racemization in aqueous buffer. In these conditions only the non-acetylated hydroxy acid is racemized. In order to obtain (S)-0-acetylmandelic acid in an 80% isolated yield and a >98% e.e. the process must be repeated four times [9]. 

Few studies have investigated links between salivary enzymes and caries or calculus. Neither Ruan et al. [97] nor Stuchell and Mandel [114] could find differences in lysozyme levels between caries-resistant and caries-susceptible subjects. On the other hand, Mandel [84] found significantly less lysozyme in submandibular saliva from heavy calculus-formers than from non-calculus formers, and a similar trend in acid phosphatase level was almost significant. Mandel speculated that lysozyme, by its interaction with cell walls [106], might modify initial calcification processes. 

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