Synthesis of chiral α-amino acids

A novel method for the synthesis of chiral α-amino acids has been developed where the acid functionality was constructed by oxidizing a hydroxymethyl group introduced by Evans’ method in the α-position of an appropriate acid substrate and the amino part came from the amide of the original carboxyl group following a modified Hofmann rearrangement reaction.     

Synthesis of highly enantiomerically enriched N-Boc-α-amino ketones from pseudoephedrine N-Boc-α-amino acid amides

N-Boc-α-amino ketones are synthesized efficiently and in high enantiomeric excess by the addition of organolithium and Grignard reagents to pseudoephedrine amides of N-Boc-α-amino acids, themselves available by the alkylation of pseudoephedrine glycinamide followed by N- protection.     

Synthesis of novel N-protected β-amino nitriles: study of their hydrolysis involving a nitrilase-catalyzed step

Several commercially available nitrilases were investigated with regard to their potential to hydrolyze N-protected β³-amino nitriles into their corresponding N-protected β³-amino acids.The biotransformations were obtained in different proportions depending on the nitrilase involved. The best hydrolysis results were achieved for the N-Cbz-β³-amino nitrile from l-alanine using the NIT-107, in a phosphate buffer at 0.05 M. However, no biotransformation into the corresponding acids was observed for the N-sulfonylamide β³-amino nitriles. Two simple and efficient procedures to prepare the β³-amino nitriles from their analogous α-amino acids are described. Thirty four new substances were synthesized and characterized over the course of this work.     

Preparation of α-amino ketones, β-amino hydroxylamines using asymmetric aza-Henry reactions of N-p-tolylsulfinylimines with nitroethane

N-Sulfinylimines derived from aromatic and aliphatic aldehydes react with nitroethane and NaOH, yielding mainly two diastereoisomeric β-nitroamines as the result of a highly diastereoselective reaction and further epimerization of the carbon linked to the nitro group. The resulting β-nitroamines are used as precursors of N-sulfonyl α-amino methyl ketones and β-amino hydroxylamines.     

Transformations of N-heteroarylformamidines into derivatives of β-heteroarylamino-α,β-dehydro-α-amino acids, β-heteroarylamino-α-amino acids,and dipeptides

Transformations of N'-heteroaryl-N,N-dimethylformamidines 1 as a general method for the preparation of β-heteroarylamino-α,β-dehydro-α-amino acids, β-heteroarylamino-α-amino acid derivatives 5–9 , and dipeptides 10 , are described.     

An improved practical synthesis of protected α-amino selenocarboxylates and its application to the synthesis of N-(α-aminoacyl)sulfonamides

An improved practical synthetic method was developed for the preparation of selenocarboxylates of amino acids through the reaction of the corresponding activated esters with sodium hydrogen selenide in alcoholic or aqueous medium. The protected α-amino selenocarboxylates reacted readily with sulfonyl azide to form N-(α-aminoacyl)sulfonamides in high yields. The commonly used protecting groups in amino acid and peptide chemistries are well tolerated under these reaction conditions. No protecting groups are needed for the side chains of Arg, Met, Ser, Tyr, and Trp.     

Transformations des énamines α-formylées: synthèse d’α-amino esters N,N-disubstitués

2-Dialkylaminoalkanoic esters are prepared in moderate yield by the reaction of N,N-disubstituted 2-amino-2-alkenals with dialkyl phosphonates in the presence of sodium alcoxide. A mechanism involving an α-keto-β-aminophosphonate as an intermediate is proposed.     

Chemoselective Synthesis of β‐Amino Ester or β‐Lactam via Sonochemical Reformatsky Reaction

A series of β‐amino esters were synthesized by the reaction of N‐tosyl aldimine or N‐hydroxy aldimine with bromoacetate by sonochemical Reformatsky reaction. The β‐N‐hydroxyamino ester was obtained and the formed sensitive hydroxylamino functionality was resistant under the reaction condition. The β‐lactam also was synthesized by the reaction of N‐p‐methoxy aldimine as reacting substrate under this sonochemical Reformatsky reaction condition.     

The synthesis of β-heteroarylamino-α,β-dehydro-α-amino acid and β-heteroarylamino-α-amino acid derivatives

From heteroarylaminomethyleneoxazolones 4 , obtained from N-heteroarylformamidines 2 and 2-phenyl-5-oxo-4,5-dihydro-1,3-oxazole ( 3 ), the following β-heteroarylamino-α,β-dehydro-α-amino acid derivatives were prepared: methyl 8 and ethyl esters 9 , amides 10 and 11 , hydrazides 12 , and azides 15 . By catalytic hydrogenation the compounds 4 were converted into β-heteroarylamino substituted amides 18 and β-heteroarylamino-α-amino acids 20 .     

Synthesis of aryl β-D-glucopyranosides and aryl β-D-glucopyranosiduronic acids

Tetra-O-benzyl--D-glucopyranosyl bromide in dichloromethane reacts stereospecifically with solutions of phenols in aqueous sodium or potassium hydroxide, in the presence of phase transfer catalysts, to give good yields of tetra-O-benzyl aryl-β-D-glucopyranosides which are converted into the corresponding aryl β-D-glucopyranosiduronic acids by sequential catalytic debenzylation and catalytic oxidation.     

β‐Lactam Synthesis through Diodomethane Addition to Amide Dianions

We present a novel route for the quick and easy synthesis of a broad range of β‐lactams. The synthesis involves a [3+1] cyclization of amide dianions with diiodomethane. In contrast to the seminal work of Hirai et al. from 1979, the reaction proved to be a general and efficient approach towards azetidinones. The ease of the process was confirmed by DFT calculations and its power demonstrated by a diversity‐oriented synthesis of β‐lactams with four points of diversity determined by the choice of Ugi adducts as starting materials.     

Synthesis of a well-defined cyclic polystyrene via α-carboxyl, ω-amino heterodifunctional polystyrene

Living anionic polymerization of styrene was carried out in benzene at room temperature using 1-(3-lithiopropyl)-4-methyl-2,6,7-trioxabicyclo[2.2.2]octane and 2,2,5,5-tetramethyl-1-(3-bromopropyl)-1-aza-2,5-disilacyclopentane as an initiator and terminator, respectively, to obtain α-2,2-bis(hydroxymethyl)propoxycarbonyl, ω-amino heterodifunctional polystyrene. It was hydrolyzed to α-carboxyl, ω-amino heterodifunctional polystyrene which gave a well-defined cyclic polystyrene by the intramolecular cyclization under high dilution conditions. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 2027–2033, 1999     

15N NMR spectroscopy acids: 7—solvent effects on α-and ω-amino

The natural abundance ¹⁵N NMR spectra of several α-and ω-amino acids were measured in various protic solvents. Increasing acidity of the solvents results in an upfield shift in the case of the α-amino acids, while ω-amino acids are almost insensitive to solvent effects.     

Highly stereocontrolled boron-mediated synthesis of β-hydroxy-α-amino acids and dipeptides. Part 2

The chiral synthons 1(a–d) were submitted to boron-mediated asymmetric aldol condensation with acetaldehyde and benzaldehyde providing, in high diastereomeric excess (>95%), R,R-configured aldols 2(a–f) which are useful intermediates to enantiomerically pure β-hydroxy-α-amino acids.     

η-Pentamethylcyclopentadienylruthenium(II) complexes containing η-coordinated α-amino acids

Reaction of [Cp* RuCl₂]₂ with -alanine ( -alaH) in methanol at room temperature in the presence of NaOMe yields the complex Na[Cp* RuCl( -ala)] (1), which contains a five-membered N,O-coordinated chelate ring. The analogous complex Na[Cp* RuCl( -phe)] (2) is obtained under similar conditions but at 0°C in 90% yield. At temperatures above 20°C both 2 and the η⁶-coordinated complex [Cp* Ru( -pheH)]Cl (4) are obtained, with the proportion of the latter increasing with temperature. Compound 4 is obtained in 88% yield by refluxing [Cp* RuCl₂]₂ and -phenylalanine ( -pheH) in CH₃OH/CH₃ONa followed by separation from 2. The analogous ruthenium(II) sandwich complexes 5–10 were obtained from -tyrosine and -tryptophane and various derivatives. [Cp* Ru( -met)] (3), prepared by the reaction of [Cp* RuCl₂]₂ with -methionine ( -metH) in CH₃OH/CH₃ONa, displays N,O,S-coordination.