- One-step preparation of enantiopure l- or d-amino acid benzyl esters avoiding the use of banned solvents
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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 α-side chain as expressed by Taft’s substituent constant (σ*).
- Bolchi, Cristiano,Bavo, Francesco,Pallavicini, Marco
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p. 965 - 974
(2017/04/11)
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- MATRIPTASE INHIBITORS AND USES THEREOF AGAINST ORTHOMYXOVIRIDAE INFECTIONS
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The present invention provides matriptase inhibitors and compositions for treating and preventing orthomyxovirus infections such as flu infections. The present invention also provides novel compounds, compositions, methods of use, uses and kits thereof for inhibiting matriptase. Such compounds are useful for treating and preventing orthomyxovirus infections, such as flu infections, and for inhibiting tumor growth, progression and/or metastasis.
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Paragraph 0308
(2016/05/02)
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- Asymmetric α-2-tosylethenylation of N,N-dialkyl-l-amino acid esters via the formation of non-racemic ammonium enolates
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Asymmetric α-2-tosylethenylation of (S)-2-(pyrrolidin-1-yl)propanoic acid esters was shown to produce good yields with high enantioselectivities. The reaction proceeds via the formation of a non-racemic ammonium enolate without an external source of chirality.
- Tayama, Eiji,Igarashi, Tomohito,Iwamoto, Hajime,Hasegawa, Eietsu
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supporting information; experimental part
p. 339 - 345
(2012/01/19)
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- Esterification of unprotected a-Amino acids in ionic liquids as the reaction media
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Ionic liquid 1,3-dimethylimidazolium methanesulfonate was used to prepare a-amino acids benzylic esters from unprotected amino acids and benzyl chloride. Esterification of several amino acids was achieved with satisfactory yields: by-products can be removed by a simple work-up procedure to afford the pure product. The described method is simple, mild, rapid and save.
- Biondini, Daniele,Brinchi, Lucia,Germani, Raimondo,Goracci, Laura,Savelli, Gianfranco
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experimental part
p. 39 - 44
(2010/08/22)
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- PROCESS FOR PRODUCTION OF OPTICALLY ACTIVE ALPHA-AMINO ACID BENZYL ESTER
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A method of producing optically active α-amino acid benzyl esters comprising reacting an optically active α-amino acid and benzyl alcohols in the presence of an acid, wherein the reaction is carried out under reduced pressure without substantially using a solvent, while distilling off water generated by the progress of the reaction.
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Page/Page column 6
(2009/06/27)
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- Application of phosphoramidate ProTide technology significantly improves antiviral potency of carbocyclic adenosine derivatives
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We report the application of phosphoramidate pronucleotide (ProTide) technology to the antiviral agent carbocyclic L-d4A (L-Cd4A). The phenyl methyl alaninyl parent ProTide of L-Cd4A was prepared by Grignard-mediated phosphorochloridate reaction and resulted in a compound with significantly improved anti-HIV (2600-fold) and HBV activity. We describe modifications of the aryl, ester, and amino acid regions of the ProTide and how these changes affect antiviral activity and metabolic stability. Separate and distinct SARs were noted for HIV and HBV. Additionally, ProTides were prepared from the D-nucleoside D-Cd4A and the dideoxy analogues L-CddA and D-CddA. These compounds showed more modest potency improvements over the parent drug. In conclusion, the ProTide approach is highly successful when applied to L-Cd4A with potency improvements in vitro as high as 9000-fold against HIV. With a view to preclinical candidate selection we carried out metabolic stability studies using cynomolgus monkey liver and intestinal S9 fractions.
- McGuigan, Christopher,Hassan-Abdallah, Alshaimaa,Srinivasan, Sheila,Wang, Yikang,Siddiqui, Adam,Daluge, Susan M.,Gudmundsson, Kristjan S.,Zhou, Huiqiang,McLean, Ed W.,Peckham, Jennifer P.,Burnette, Thimysta C.,Marr, Harry,Hazen, Richard,Condreay, Lynn D.,Johnson, Lance,Balzarini, Jan
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p. 7215 - 7226
(2007/10/03)
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- Synthesis and in vitro antibacterial activity of catechol-spiramycin conjugates
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The first synthesis of siderophore conjugates of two macrolide antibiotics, spiramycin 1 and neospiramycin 2, which are unable to penetrate the outer membrane of Gram-negative bacteria are described. These novel conjugates were prepared by regioselective acylation of a hydroxyl function of 1 and 2 with a dihydroxybenzoic Fe(III) complexing ligand linked via a carboxyl group containing spacer to the macrolide antibiotics. The preliminary biological evaluation of these novel conjugates under standard and iron depleted conditions has shown that their antibacterial activity was comparable to that of spiramycin 1 and neospiramycin 2.
- Poras, Herve,Kunesch, Gerhard,Barriere, Jean-Claude,Berthaud, Nadine,Andremont, Antoine
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p. 786 - 794
(2007/10/03)
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- Application of 4-Polystyryltriphenylmethyl Chloride to the Syntheses of Peptides and Amino Acid Derivatives
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Use of polymer-bound trityl chloride as an α-amino protecting group of amino acids allows simple and high-yield syntheses of amino acid derivatives and peptides.
- Barlos, Kleomenis,Gatos, Dimitrios,Kallitsis, Ioannis,Papaioannou, Dionysios,Sotiriou, Petros
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p. 1079 - 1082
(2007/10/02)
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