One-step preparation of enantiopure L- or D-amino acid benzyl esters avoiding the use of banned solvents

The enantiomers of amino acid benzyl esters are very important synthetic intermediates. Many of them are currently prepared by treatment with benzyl alcohol and p-toluenesulfonic acid in refluxing benzene or carbon tetrachloride, to azeotropically remove water, and then precipitated as tosylate salt by adding diethyl ether. Here, we report a very efficient preparation of eight l- or d-amino acid benzyl esters (Ala, Phe, Tyr, Phg, Val, Leu, Lys, Ser), in which these highly hazardous solvents are dismissed using cyclohexane as a water azeotroping solvent and ethyl acetate to precipitate the tosylate salt. With some work-up modifications and lower yield, the procedure can be applied also to methionine. Chiral HPLC analysis shows that all the benzyl esters, including the highly racemizable ones such as those of phenylglycine, tyrosine and methionine, are formed enantiomerically pure under these new reaction conditions thus validating the solvents replacement. Contrariwise, toluene cannot be used in place of benzene or carbon tetrachloride because leading to partially or totally racemized amino acid benzyl esters depending on the polar effect of the amino acid \u3b1-side chain as expressed by Taft\u2019s substituent constant (\u3c3*)

ENANTIOPURI, senza usare solventi ‘HH’

Gli amminoacidi con BnOH e p-TsOH in benzene o CCl4 a riflusso danno l\u2019estere benzilico salificato enantiomericamente puro. Se si usa toluene, in sostituzione di questi solventi \u2018highly hazardous\u2019 (HH), l\u2019estere racemizza. Il cicloesano \ue8, invece, una valida alternativa: acido aspartico ed acido glutammico ne sono un esempio

seasonal abundance of the nearctic gall midge obolodiplosis robiniae in italy and the impact of its antagonist platygaster robiniae on pest populations

The Nearctic gall midge Obolodiplosis robiniae (Haldeman, 1847) (Diptera Cecidomyiidae) infesting black locusts, Robinia pseudoacacia L. (Fabaceae), was detected in Asia in 2002 and in Europe (first in Italy) in 2003. Its distribution in Europe has expanded dramatically, probably favored by extensive distribution of its host plant along the main routes. The results of a 3-yr study on the seasonal abundance of O. robiniae in northern Italy are reported here. O. robiniae can develop three to four generations per year by exploiting plants of different ages and vigor. Overwintering takes place as diapausing larvae and adults emerge in spring. Two generations are completed on mature plants where populations decline in summer. Two additional generations can develop on root suckers from midsummer onward. Pest population densities reach their highest levels in late spring. Gall midge larvae were attacked by various predators, but parasitism by the platygastrid Platygaster robiniae Buhl & Duso was particularly significant. The impact of parasitism by P. robiniae is indicated as a key factor in reducing O. robiniae population densities

Role of sortase-dependent pili of Bifidobacterium bifidum PRL2010 in modulating bacterium-host interactions

Bifidobacteria represent one of the dominant groups of microorganisms colonizing the human infant intestine. Commensal bacteria that interact with a eukaryotic host are believed to express adhesive molecules on their cell surface that bind to specific host cell receptors or soluble macromolecules. Whole-genome transcription profiling of Bifidobacterium bifidum PRL2010, a strain isolated from infant stool, revealed a small number of commonly expressed extracellular proteins, among which were genes that specify sortase-dependent pili. Expression of the coding sequences of these B. bifidum PRL2010 appendages in nonpiliated Lactococcus lactis enhanced adherence to human enterocytes through extracellular matrix protein and bacterial aggregation. Furthermore, such piliated L. lactis cells evoked a higher TNF-α response during murine colonization compared with their nonpiliated parent, suggesting that bifidobacterial sortase-dependent pili not only contribute to adherence but also display immunomodulatory activity

Role of sortase-dependent pili of Bifidobacterium bifidum PRL2010 in modulating bacterium-host interactions

Bifidobacteria represent one of the dominant groups of microorganisms colonizing the human infant intestine. Commensal bacteria that interact with a eukaryotic host are believed to express adhesive molecules on their cell surface that bind to specific host cell receptors or soluble macromolecules. Whole-genome transcription profiling of Bifidobacterium bifidum PRL2010, a strain isolated from infant stool, revealed a small number of commonly expressed extracellular proteins, among which were genes that specify sortase-dependent pili. Expression of the coding sequences of these B. bifidum PRL2010 appendages in nonpiliated Lactococcus lactis enhanced adherence to human enterocytes through extracellular matrix protein and bacterial aggregation. Furthermore, such piliated L. lactis cells evoked a higher TNF-\u3b1 response during murine colonization compared with their nonpiliated parent, suggesting that bifidobacterial sortase-dependent pili not only contribute to adherence but also display immunomodulatory activity

1H NMR spectroscopy in the presence of Mosher acid to rapidly determine the enantiomeric composition of amino acid benzyl esters, chirons susceptible to easy racemization

Amino acid benzyl esters are very useful chiral synthons, whose enantiomeric purity needs to be carefully verified because of their susceptibility to easy racemization. Alternative to chiral HPLC,1H NMR in the presence of a chiral solvating agent (CSA) can allow a more rapid and acceptably accurate determination of the enantiomeric composition, if explicit spectral non-equivalence of one or more protons of the analyte enantiomers is found. Here, we have studied the enantiodiscrimination of 13 amino acid benzyl esters by1H NMR in the presence of (R)-Mosher acid and in different solvents proving that, for 5 of them (Ala, Pro, Glu, Met, Ser), efficient enantiodifferentiation can be achieved and 64 98% enatiomeric excesses accurately determined. Generally, as expectable, the best enantiodifferentiated proton was that on the amino acid stereogenic \u3b1-carbon, but also the spectral non-equivalence of methyl protons and of protons on the \u3b2-carbon and on the benzylic carbon could be exploited to distinguish the two enantiomers and to quantify the minor one. Structural feature favoring the amino acid ester enantiodiscrimination by the CSA seems to be low sterical hindrance at the amino acid \u3b2-carbon

A simple route to synthesize (E)-3 propyl-4-oxo-2-butenoic acid esters through the Z isomer

Esters of 3-alkyl-2-oxo-4-butenoic acid, which are very important synthons, are not equally accessible in both E and Z configuration. The Z isomers can be easily obtained from 3-alkyl-4-hydroxybutenolides, in turn prepared by aminoalkylation of aliphatic aldehydes with glyoxylic acid. The E isomers, on the contrary, result from laborious procedures: the condensation of aldehydes with glyoxylic acid, followed by separation from \u3b3-hydroxybutenolide by-product and esterification, or of aldehydes enamines with glyoxylic esters, followed by Z ester by-product conversion into \u3b3-aminobutenolide and purification. Here, we describe a straightforward route to the title compounds, applied to methyl (E)-3-propyl-4-oxo-2-butenoate, avoiding any problematic by-product or isomer chromatographic separation: pentanal and glyoxylic acid are condensed to 3-propyl-4-hydroxybutenolide, which is converted to methyl (Z)-3-propyl-4-oxo-2-butenoate and then isomerized to the E ester under acidic conditions

Phase Diagrams to Evaluate the Opportunity for Enantiomeric Enrichment of Some Nonracemic Mixtures of Amino Acid Benzyl Esters by Crystallization as p-Toluenesulfonate Salts

A number of amino acids undergo moderate-to-high racemization when converted to benzyl ester under inadequate conditions. As they are usually recovered and purified at the end of the esterification by precipitating/crystallizing the p-toluenesulfonate salt, it is of most importance to be aware that such isolation procedures can improve but also lessen the enatiomeric excess of the product. To predict the chance of enantioenrichment by crystallization, it is necessary to define whether the enantiomers of these ester salts form conglomerates or racemic compounds in the solid state and, in case of racemic compounds, to know the enantiomeric composition of the eutectics and to verify that it is similar to the eutectic composition obtained from ternary solubility curves. We constructed the binary melting point phase diagrams of a number of amino acid benzyl ester p-toluenesulfonates showing that most of them form racemic compounds. Of these, we studied those of Ala, Phe, Leu, and Glu, in particular, demonstrating that when prepared in l form with moderate racemization the first three cannot be enantioenriched by crystallization because their l fraction is much higher at the ternary solubility eutectic than at the binary eutectic, whereas the last one can be isolated enantiopure by crystallization because its l fractions at both the ternary solubility and binary eutectics are accordingly low