Protected Α-amino Acids Research Articles

Convenient and simple homologation ofN α-urethane protected α-amino acids to their β-homologues with concomitant pentafluorophenyl ester formation

Convenient and simple homologation ofN α-urethane protected α-amino acids to their β-homologues with concomitant pentafluorophenyl ester formation

Reactions of Alkyl Radicals with Oxime Ether: One-Pot Synthesis of α-Amino Acids

The addition of water-resistant carbon radicals to glyoxylic oxime ether provided a new method for the one-pot synthesis of α-amino acids via a carbon–carbon bond formation. The reaction of 2-hydroxy-2-methoxyacetic acid methyl ester with benzyloxyamine and an alkyl radical gave the protected α-amino acids via the stannyl radical-mediated reaction. In the absence of Bu 3SnH, the predominant formation of the desired alkylated products was also observed by using RI and Et 3B in boiling toluene. Et 2Zn could serve as an initiator of these radical reactions as well as Et 3B.

Convenient and simple homologation of Nα-urethane protected α-amino acids to their β-homologues with concomitant pentafluorophenyl ester formation

The Wolff rearrangement of α-aminodiazoketonesderived from Nα-urethane protected α-amino acids in the presence of pentafluorophenol catalyzed by silver acetate at low temperature results in the homologation of Fmoc-/Boc-/Z-α-amino acids to β-amino acids withconcomitant formation of the corresponding pentafluorophenylesters in good yield and purity.

Phase transfer catalysis: some recent applications in organic synthesis

A survey dealing with the use of anhydrous potassium carbonate as an efficient base for promoting organic reactions under solid–liquid phase transfer catalysis (SL-PTC) conditions is reported. In particular, the generation in situ of trifluoro- and trichloroacetamidide, and reactions of these azaanions with 2-bromocarboxylic esters and epoxides, affording protected α-amino acids and β-amido alcohols, respectively, are described. The reduction of allylic nitroderivatives with CS 2 to oximes or nitriles under SL- and liquid–liquid PTC (LL-PTC) is also presented. Finally, new preparation methods and a study of the reactivity of quaternary onium fluorides, hydrogendifluorides and dihydrogentrifluorides, together with the use of dihydrogentrifluorides as hydrofluorinating agents under SL-PTC conditions, are reported.

Effect of the Amide Connecting Tether Type of Pirkle-Concept Chiral Stationary Phases Derived from (S)-N-(3,5-Dinitrobenzoyl)Leucine on Enantiomeric Separations

ABSTRACT Liquid chromatographic comparisons are made between a secondary amide linked chiral stationary phase (CSP 1) and a tertiary amide double-tethered CSP (CSP 2) derived from (S)-N-3,5-[dinitrobenzoyl(DNB)]leucine. For the enantioseparation of the anilide derivatives of N-9-fluorenylmethoxycarbonyl (FMOC), benzyloxycarbonyl (CBZ) and t-butoxycarbonyl (BOC) protected α-amino acids, CSP 2 shows performance superior to that of CSP 1. It is considered that the amide hydrogen of the connecting tether of CSP 1 serves as a nonproductive adsorption site, while the enhanced basicity of the carbonyl oxygen of the tertiary amide tethered CSP 2 is responsible for the increased enantioselectivity of these analytes. For the same reason, it is observed that CSP 2 provides better separation of the enantiomers of N-CBZ α-amino acids as ethyl ester, n-butylamide and diethylamide derivatives than CSP 1.

Synthesis of cyanoketophosphoranes, precursors of β-amino-α-keto-esters from UNCAs

Cyanomethylene triphenylphosphoranes of N-protected amino acids were synthesized from the corresponding N-urethane protected α-amino acid N-carboxyanhydrides (UNCAs) by reaction with cyanomethyltriphenylphosphonium chloride in good yields. These compounds are precursors of α-keto esters which are candidates for mimicking the tetrahedric transition state in enzyme inhibitors.

Dynamic Kinetic Resolutions Catalyzed by a Planar-Chiral Derivative of DMAP: Enantioselective Synthesis of Protected α-Amino Acids from Racemic Azlactones

Dynamic Kinetic Resolutions Catalyzed by a Planar-Chiral Derivative of DMAP: Enantioselective Synthesis of Protected α-Amino Acids from Racemic Azlactones

One-pot synthesis of α-amino acids based on free radical-mediated carbon–carbon bond formation

The one-pot reaction of 2-hydroxy-2-methoxyacetic acid methyl ester with benzyloxyamine and an alkyl radical provided a convenient method for preparing the protected α-amino acids via a carbon–carbon bond formation by intermolecular carbon radical addition to glyoxylic oxime ether.

Highly Practical Methodology for the Synthesis ofd- andl-α-Amino Acids,N-Protected α-Amino Acids, andN-Methyl-α-amino Acids

Full details are provided for an exceedingly practical method to synthesize d- and l-α-amino acids, N-protected α-amino acids, and N-methyl-α-amino acids, employing as a key step the asymmetric alkylation of pseudoephedrine glycinamide (1) or pseudoephedrine sarcosinamide (2). Practical procedures for the synthesis of 1 and 2 from pseudoephedrine and glycine methyl ester or sarcosine methyl ester, respectively, are presented. Optimum protocols for the enolization and subsequent alkylation of 1 and 2 are described. Alkylation reactions of 1 and 2 are found to be quite efficient with a wide range of alkyl halide substrates, and the products are formed with high diastereoselectivity. The products of these alkylation reactions are hydrolyzed efficiently and with little to no racemization simply by heating in water or water−dioxane mixtures. This protocol provides an exceedingly practical method for the preparation of salt-free α-amino acids of high enantiomeric purity. Alternatively, the alkylation products may be hydrolyzed in high yield and with little to no racemization by heating with aqueous sodium hydroxide. The alkaline hydrolyzate can then be treated with an acylating reagent to provide directly highly enantiomerically enriched N-protected derivatives such as N-Boc and N-Fmoc. Key features necessary for the successful execution of these experimental procedures are identified.

Asymmetric synthesis of uncommon α-amino acids by diastereoselective alkylations of a chiral glycine equivalent

Abstract For the purpose of practical preparations of a variety of enantiomerically pure uncommon α-amino acids, alkylations of the chiral glycine equivalent 5 , which possesses axially chiral binaphthol as an auxiliary, with several electrophiles were investigated. The alkylation proceeded smoothly in satisfactory chemical yield with high diastereoselectivities to give protected α-amino acid derivatives. The free hydroxyl group of the auxiliary played an important role for the induction of diastereoselectivity. Using ( S )-1,1′-binaphthalene-2,2′-diol as a chiral auxiliary, D-α-amino acid derivatives having the unnatural ( R )-configuration were predominantly obtained. Some of the alkylated products were converted into free non-proteinogenic D-α-amino acids.

Oxidation of functional olefines: Synthesis of protected amino acids bearing a terminal α-hydroxyketo group

The osmium trichloride-catalyzed oxidation with peracetic acid of olefinic compounds bearing a protected α-amino acid group leads to α-ketol amino acid precursors related to the 5-Hydroxy-4-Oxo-Norvaline antibiotic.

Use of ( S)- N- tert-butoxycarbonylaziridine-2-carboxylate derivatives for α-amino acid synthesis

( S)- tert-Butyl- N- tert-butoxycarbonylaziridine-2-carboxylate and ( S)- tert-butyl- N- tert-butoxycarbonylaziridine-2-carboxamide were synthesised and found to react with copper ‘catalysed’ Grignard reagents to give protected α-amino acids in moderate to good yields.

The Reaction Between C- and/or N-Terminal Protected α-Aminoacid and Sodium Hydrogen Telluride

Abstract Sodium hydrogen telluride selectively removed C-terminal alkyl group of C- and/or N-terminal protected α-aminoacids with yields ranging from 70% to 95%.

Preparation of enantiomerically pure protected unsaturated α-amino acids from a new serine derived zinc–copper reagent

Treatment of the iodoalanine derived zinc reagent 1 with Knochel's soluble copper salt (CuCN·2LiCl) allows the preparation of a reactive copper reagent 2 which couples in moderate to good yield with allyl halides to give protected unsaturated α-amino acids in a single step from easily available precursors.

Preparation of AcyclicN-Acyl-N,O-acetals by Decarboxylation ofN-Protected α-Amino Acids and Studies of Asymmetric Amidoalkylation with Trimethylsilyl Cyanide

Abstract Oxidative decarboxylation of N-acyl-α-amino acids with lead tetra-acetate followed by treatment with methanol provides a facile method for preparation of acyclic N-acyl-N,O-acetals, which can be used in asymmetric α-amidoalkylation reactions using trimethylsilyl cyanide as nucleophile.

A New Method for the α-Vinylation of Protected α-Amino Acids; Ethylene Oxide as Vinyl Cation Equivalent

Abstract A convenient and conceptually new strategy for the transformation of α-amino acids into the corresponding α-vinyl amino acids is described; commercially available ethylene oxide serves as a vinyl cation equivalent.

ChemInform Abstract: Synthesis of α‐Amino Acids with β,γ‐Unsaturated Side Chains.

ChemInformVolume 20, Issue 2 Natural Products ChemInform Abstract: Synthesis of α-Amino Acids with β,γ-Unsaturated Side Chains. A. L. CASTELHANO, A. L. CASTELHANO Syntex Inc., Mississauga, Ont., Can. L5N 3X4Search for more papers by this authorS. HORNE, S. HORNE Syntex Inc., Mississauga, Ont., Can. L5N 3X4Search for more papers by this authorG. J. TAYLOR, G. J. TAYLOR Syntex Inc., Mississauga, Ont., Can. L5N 3X4Search for more papers by this authorR. BILLEDEAU, R. BILLEDEAU Syntex Inc., Mississauga, Ont., Can. L5N 3X4Search for more papers by this authorA. KRANTZ, A. KRANTZ Syntex Inc., Mississauga, Ont., Can. L5N 3X4Search for more papers by this author A. L. CASTELHANO, A. L. CASTELHANO Syntex Inc., Mississauga, Ont., Can. L5N 3X4Search for more papers by this authorS. HORNE, S. HORNE Syntex Inc., Mississauga, Ont., Can. L5N 3X4Search for more papers by this authorG. J. TAYLOR, G. J. TAYLOR Syntex Inc., Mississauga, Ont., Can. L5N 3X4Search for more papers by this authorR. BILLEDEAU, R. BILLEDEAU Syntex Inc., Mississauga, Ont., Can. L5N 3X4Search for more papers by this authorA. KRANTZ, A. KRANTZ Syntex Inc., Mississauga, Ont., Can. L5N 3X4Search for more papers by this author First published: January 10, 1989 https://doi.org/10.1002/chin.198902280Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume20, Issue2January 10, 1989 RelatedInformation

New synthesis of DL-α- aminoacids from t-butyl N(diphenylmethylene) oxamate

Reaction of oxamate 1 with phosphorus ylids gives azadienes 2 which are readily converted into protected α-aminoacids.

A new direct method for the synthesis of enantiomerically pure protected α-amino acids

The organozinc reagent (2), prepared from the protected β-iodo alanine derivative (3) using ultrasonic activation, is efficiently acylated using acid chlorides in the presence of (Ph3P)2PdCl2 to give high yields of enantiomerically pure protected γ-keto α-amino acids (4).

Synthesis of α-amino acids with β,γ-unsaturated side chains

α-Amino acids with allenyl, vinyl, and acetylenic side chains can be synthesized using non-enolate based strategies. The ester enolate-Claisen rearrangement applied to propargylic esters of N -protected α-amino acids ie of limited utility since only poor yields of allenic product are obtained with the N-Boc glycine esters, the system which give the most reproducible results. However, α-allenyl-α-amino acids that are fully functionalized on the α-carbon are available through the agency of 4-allenyl-2-phenyloxazolones 4 (obtained from propargyl esters of N-benzoyl protected amino acids via cyclization and Claisen rearrangement) provided that Meerwein's reagent is used to facilitate hydrolysis of the benzamide function in 5 . A variety, of α-substituted glycinates, including those with α-vinyl and α-acetylenic functions, can be prepared using a two-step sequence involving condensation of the cationic glycine synthon 22 with various organomagnesiu reagents, followed by hydrolysis.