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One-step Preparation Of Enantiopure L- Or D-amino Acid Benzyl Esters Avoiding The Use Of Banned Solvents

C. Bolchi, F. Bavo, M. Pallavicini
Published 2017 · Chemistry, Medicine

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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*).
This paper references
Fibrinogen peptide derivatives, US
LC Dorman (1976)
10.1021/j100686a021
Zwitterion formation upon deprotonation in L-3, 4-dihydroxyphenylalanine and other phenolic amines.
R. Martin (1971)
10.1021/J100686A021
Zwitterion formation upon deprotonation in L-3, 4-dihydroxyphenylalanine and other phenolic amines.
Martin Rb (1971)
10.1021/JM00214A010
Synthesis and structure-activity relationships of bestatin analogues, inhibitors of aminopeptidase B.
R. Nishizawa (1977)
10.1016/J.TETLET.2010.08.006
A highly efficient method for the a,-dehydrogenation of a-amino esters and a-amino--diesters
M. Pallavicini (2010)
The effect of structure and conditions on the rate of racemization of free and bound amino acids
GG Smith (1980)
10.1002/CHIN.201223193
Asymmetric α-2-Tosylethenylation of N,N-Dialkyl-L-amino Acid Esters via the Formation of Non-Racemic Ammonium Enolates.
E. Tayama (2012)
10.1021/ja904177k
Cis-trans proline isomerization effects on collagen triple-helix stability are limited.
Nan Dai (2009)
10.1021/CC0600021
Synthesis of Tetramic and Tetronic Acids as β-Secretase Inhibitors
Gregor Larbig and (2006)
10.1021/JO00280A017
Effect of the side chain on the racemization of amino acids in aqueous solution
G. G. Smith (1989)
Exploring QSAR hydrophobic, steric and electronic constants
C Hansch (1995)
10.1021/JO0111210
Synthesis of chiral pilocarpine analogues via a C-8 ketone intermediate.
Kenneth G. Holden (2002)
Process for the production of optically active alphaamino acid benzyl ester
N Hirata (2009)
10.1021/JO01362A052
Studies on Arginine Peptides. I. Intermediates in the Synthesis of N-Terminal and C-Terminal Arginine Peptides*
L. Zervas (1957)
Poly ( ester urea ) polymers and methods of use
R Katsarava (2007)
10.1002/CHIN.198314235
Studies on lactams. Part 65. N-Unsubstituted .beta.-lactams from .beta.-hydroxy-.alpha.-amino acids. Facile preparation of intermediates for isocephalosporins
A. Bose (1983)
Process for producing l-valine benzyl ester p-toluenesulfonate. EP
Y Tagami (2000)
10.1021/JE700067A
Temperature Dependence of the Dissociation Constants of Several Amino Acids
Hidetada Nagai (2008)
Synthesis of the nonatriacontapeptide
T References Abiko (1983)
10.1002/EJOC.201500589
A One‐Pot Synthesis of Symmetrical and Unsymmetrical Dipeptide Ureas
A. A. Fayad (2015)
10.1021/JA000835+
Synthesis and Assembly of Poly(ethylene glycol)−Lipids with Mono-, Di-, and Tetraacyl Chains and a Poly(ethylene glycol) Chain of Various Molecular Weights
S. Takeoka (2000)
10.1002/JLAC.19616420116
Über Peptidsynthesen, III. Synthesen von Arginin-haltigen Peptiden†‡
H. Gibian (1961)
10.1039/C5GC01008J
CHEM21 selection guide of classical- and less classical-solvents
Denis Prat (2016)
10.1002/CHIN.200237208
Synthesis of a Peptidomimetic HCMV Protease Inhibitor Library.
P. Xu (2002)
Gomurashvili ZD (2007) Poly(ester urea) polymers and methods of use
R Katsarava (2007)
10.2174/157017810790533940
Esterification of Unprotected α-Amino Acids in Ionic Liquids as the Reaction Media
D. Biondini (2010)
Process for producing l - valine benzyl ester p - toluenesulfonate
Y Tagami (2000)
10.1039/P19910001283
Biosynthesis of hyalodendrin and didethiobis(methylthio)hyalodendrin, sulphur-containing 2,5-dioxopiperazines of the 3S,6S series
M. I. P. Boente (1991)
10.1016/J.TETLET.2008.09.027
A mild Boc deprotection and the importance of a free carboxylate
Ali Thaqi (2008)
Poly(ester urea) polymers and methods of use Synthesis of tetradecapeptide corresponding to sequence 90-103 of bovine adrenodoxin
R Katsarava (1980)
10.1248/CPB.18.1794
Studies on the Racemization of Amino Acids and Their Derivatives. III. The Effect of Alkyl-, Aralkyl- and Aryl-Side Chain at α-Position of Amino Acids on Their Base-Catalyzed Racemization
Motomu Sato (1970)
10.1055/b-0035-112897
6.5 Synthesis of Phosphopeptides (II)
A. Felix (2004)
10.1021/JA00976A032
The preparation and properties of trans-cinnamoyl-papain.
L. J. Brubacher (1966)
10.7164/ANTIBIOTICS.51.786
Synthesis and in vitro antibacterial activity of catechol-spiramycin conjugates.
H. Poras (1998)
10.1016/j.bmc.2009.07.035
N-[2-chloro-9H-purin-6-yl]-N-cyclopropylglycylamino acids and derivatives: synthesis, evaluation as a class of novel analgesics, and 3D QSAR analysis.
JingHua Zhao (2009)
10.1021/JO991051L
Enantioselective inclusion of methyl phenyl sulfoxides and benzyl methyl sulfoxides by (R)-phenylglycyl-(R)-phenylglycine and the crystal structures of the inclusion cavities
Akazome (2000)
10.1021/jo00142a015
Studies on lactams. Part 65. N-Unsubstituted .beta.-lactams from .beta.-hydroxy-.alpha.-amino acids. Facile preparation of intermediates for isocephalosporins
A. Bose (1982)
Fibrinogen peptide derivatives
Lc Dorman (1976)
10.1002/chin.197950142
Dipeptides of O-methyl-L-threonine as potential antimalarials
H. Gershon (1979)
10.1002/CHIN.201011149
Microwave‐Assisted Synthesis of Pyridylpyrroles from N‐Acylated Amino Acids.
Kirsi Harju (2010)
10.1016/J.BMCL.2007.09.015
Peptidomimetic inhibitors of farnesyltransferase with high in vitro activity and significant cellular potency.
C. Bolchi (2007)
10.1021/JA01592A022
Studies on Diastereoisomeric α-Amino Acids and Corresponding α-Hydroxy Acids. VII. Influence of β-Configuration on Enzymic Susceptibility
M. Winitz (1956)
Synthesis and structure-activity relationships of bestatin analogues, inhibithors of aminopeptidase B
R Nishizawa (1977)
10.1002/JPS.2600690938
Substituent Constants for Correlation Analysis in Chemistry and Biology.
G. Flynn (1980)
10.1055/S-1991-26399
Synthesis and Spectroscopic Properties of Azaglutamine Amino Acid and Peptide Derivatives
C. J. Gray (1991)
10.1021/jo00149a024
A simple and convenient method for esterification of tryptophan and other amino acids
I. Arai (1983)
Optically active amino acid derivatives and processes for the preparation of the same
H Sato (2004)
A one-pot synthesis of symmetrical and unsymmetrical dipeptide ureas Synthesis of phosphopeptides
Aa Fayad (1959)
10.1248/CPB.15.391
Studies on the racemization of amino acids and their derivatives. I. On the deuterium-hydrogen exchange reaction of amino acids derivatives in basic media.
M. Masayuki (1967)
Synthesis of tetramic and tetronic acids as beta-secretase inhibitors.
G. Larbig (2006)
Biosynthe - sis of hyalodendrin and didethiobis ( methylthio ) hyalodendrin , sulfur - containing 2 , 5 - dioxopiperazines of the 3 S , 6 S series
Boente MIP (1991)
Synthesis of aminoacid benzyl ester p-toluenesulfonates
N Izumiya (1957)
10.1002/CHIN.199134250
Biosynthesis of Hyalodendrin and Didethiobis(methylthio)hyalodendrin, Sulfur-Containing 2,5-Dioxopiperazines of the 3S,6S Series.
M. I. P. Boente (1991)
10.1002/chir.21982
Enantiomeric resolution of p-toluenesulfonate of valine benzyl ester by preferential crystallizaion.
T. Munegumi (2012)
2015b) Chemistry and pharmacology of a series of unichiral analogues of 2-(2-pyrrolidinyl)-1,4-benzodioxane, prolinol phenyl ether, and prolinol 3-pyridyl ether
C Bolchi (2015)
10.1002/CHIN.200540050
Synthesis of a Library Chiral α‐Amino Acid‐Based Borate Counteranions and Their Application to Copper Catalyzed Olefin Cyclopropanation.
D. Llewellyn (2005)
10.3987/COM-88-S108
Use of the Barton Decarboxylation Procedure in Indole Alkaloid Chemistry
P. Magnus (1989)
10.1002/CHIN.199331131
Chirospecific Synthesis of (1S,3R)‐1‐Amino‐3‐(hydroxymethyl) cyclopentane, Precursor for Carbocyclic Nucleoside Synthesis. Dieckmann Cyclization with an α‐Amino Acid.
S. Bergmeier (1993)
10.1021/JA00728A033
Determination of D- and L-amino acid residues in peptides. Use of tritiated hydrochloric acid to correct for racemization during acid hydrolysis.
J. Manning (1970)
10.1021/JA00759A064
Kinetics of racemization of amino acids as a function of pH.
J. L. Bada (1972)
10.1021/JF00069A047
Racemization kinetics of free and protein-bound amino acids under moderate alkaline treatment
R. Liardon (1986)
10.1016/J.TETASY.2005.04.004
Synthesis of a library of chiral α-amino acid-based borate counteranions and their application to copper catalyzed olefin cyclopropanation
D. Llewellyn (2005)
10.1021/JA01530A041
The Use of p-Nitrobenzyl Esters in Peptide Synthesis1
H. Schwarz (1959)
10.1039/b814804j
Primary amino acid lithium salt as a catalyst for asymmetric Michael addition of isobutyraldehyde with beta-nitroalkenes.
A. Sato (2008)
10.1016/J.BMC.2007.06.012
A new class of anti-thrombosis hexahydropyrazino-[1',2':1,6]pyrido-[3,4-b]-indole-1,4-dions: design, synthesis, logK determination, and QSAR analysis.
Jiawang Liu (2007)
10.1021/jm970475
Effect of stereochemistry on the clearance mechanism of 111In(III)-labeled D- or L-benzyldiethylenetriaminepentaacetic acid.
K. Deal (1997)
10.1021/acs.jmedchem.5b00904
Chemistry and Pharmacology of a Series of Unichiral Analogues of 2-(2-Pyrrolidinyl)-1,4-benzodioxane, Prolinol Phenyl Ether, and Prolinol 3-Pyridyl Ether Designed as α4β2-Nicotinic Acetylcholine Receptor Agonists.
C. Bolchi (2015)
Solid-phase synthesis of 4-methylcarbpxy-1,4-benzodiaz- epine-2,5-diones
P Verdié (2008)
10.1246/NIKKASHI1948.78.662
アミノ酸のベンジルエステル-P-トルエンスルホン酸塩の合成
信夫 泉屋 (1957)
10.1002/JHET.1578
Concise Synthesis of α‐Methylene‐β‐hydroxy‐γ‐carboxy‐γ‐lactams
Srinivas Tekkam (2013)
10.1002/CHIN.198048297
SYNTHESIS OF A TETRADECAPEPTIDE CORRESPONDING TO SEQUENCE 90-103 OF BOVINE ADRENODOXIN
K. Kawasaki (1980)
10.1016/j.bmc.2010.03.045
Azetidinone-isothiazolidinones: stereoselective synthesis and antibacterial evaluation of new monocyclic beta-lactams.
Helena Cerić (2010)
10.1002/chin.198331103
MECHANISM OF THE RACEMIZATION OF AMINO ACIDS. KINETICS OF RACEMIZATION OF ARYLGLYCINES
G. G. Smith (1983)
10.1021/ACS.OPRD.5B00134
Enantiomerically Pure Dibenzyl Esters of l-Aspartic and l-Glutamic Acid
C. Bolchi (2015)
10.1039/A903956B
Supramolecular receptors from α-amino acid-derived lipids
H. Hachisako (1999)
A (2010) Azetidinone-isothiazolidinones: stereoselective synthesis and antibacterial evaluation of new monocyclic betalactams
H Cerić (2010)
10.1248/CPB.31.1320
Synthesis of the nonatriacontapeptide corresponding to the entire amino acid sequence of calf thymosin beta 8 and its effect on the impaired T-cell subsets in patients with lupus nephritis.
T. Abiko (1983)
10.1021/cc800085d
Solid-phase synthesis of 4-methylcarboxy-1,4-benzodiazepine-2,5-diones.
P. Verdié (2008)
10.1016/j.bmc.2010.01.038
Benzyl 1,2,3,5,11,11a-hexahydro-3,3-dimethyl-1-oxo-6H-imidazo[3',4':1,2]pyridin[3,4-b]indole-2-substituted acetates: One-pot-preparation, anti-tumor activity, docking toward DNA and 3D QSAR analysis.
Jiawang Liu (2010)
Endothelin antagonists. US, 6162927 Arai I, Muramatsu I (1983) A simple and convenient method for esterification of tryptophan and other amino acids
M Winn (1997)
10.3891/ACTA.CHEM.SCAND.13-1407
Synthesis of Phosphopeptides. II. O-Phosphorylated Dipeptides of L-Serine.
G. Foelsch (1959)
10.1021/JM970475+
Effect of stereochemistry on the clearance mechanism of 111In(III)-labeled D- or L-benzyldiethylenetriaminepentaacetic acid.
K. Deal (1997)
10.1248/CPB.18.1788
Studies on the Racemization of Amino Acids and Their Derivatives. II. On the Deuterium-Hydrogen Exchange Reaction of Amino Acid Derivatives in a Medium of Deuterated Acetic Acid
H. Matsuo (1970)
The effect of structure and conditions on the rate of racemization of free and bound amino acids Biogeochemistry of amino acids
Gg Smith (1980)
10.1039/C5QO00298B
Stereodivergent and enantioselective total syntheses of isochaetominines A–C and four pairs of isochaetominine C enantiomers: a six-step approach
Zhong-Yi Mao (2016)
Peptide syntheses.III: syntheses of arginine-containing peptides
H Gibian (1961)
10.1021/JO00349A028
Esterification of N-protected .alpha.-amino acids with alcohol/carbodiimide/4-(dimethylamino)pyridine. Racemization of aspartic and glutamic acid derivatives
M. Dhaon (1982)



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