N-Protection of amino acids

Characterization or N-protection of amino acids by the f-butyloxycarbonyl group can be carried out either by acyl transfer from the triazole (335) prepared as in Scheme 144 or with t-butyl phenylcarbonate in the presence of triazole (73TL469) in lower yields. Although 1,2,4-triazole acts as a catalyst in the second of these reactions, it has to be present in an equimolar amount. 

Table 1 Urethane-Type Protecting Groups Most Frequently Used for N -Protection of Amino Acids...

Amongst the previously proposed AT-sulfonyl derivatives, the Mtr group has most frequently been used for the side-chain protection of lysine,although it has occasionally been used for N -protection of amino acids.It is cleaved by strong acids such as 0.3 M methane-sulfonic acid in TFA/thioanisole (9 1) at room temperature within 1 hour.t l... 

More recently, the 2-(trifluoroacetyl)vinyl group (4,4,4-trifluoro-3-oxobut-l-enyl, 126) was proposed for the N-protection of amino acids.This enamine derivative is readily prepared with 4-ethoxy-l,l,l-trifluorobut-3-en-2-one and NaOH at room temperature in 1-3 hours. Acidic workup leads to the protected amino acids in yields ranging from 70-89% without racemization. Cleavage is achieved with 3 M HCl in dioxane at room temperature in 10 hours. 

N-Protection of amino acids (3, 36). /-Butyloxycarbonyl (BOC) amino acids (2) can be prepared in 80-100% yield by the reaction of 1,1,3,3-tetramethylguanidinium salts of amino acids (1) with /-butyl azidoformate in DMF.2... 

N-ProtecUve group. Although the trityl group has received some consideration for the N-protection of amino acids, a serious limitation is that, with the exception of the glycine derivative, the p-nitrophenyl esters of N-tritylamino acids do not couple with amino acid esters. ... 

Peptide synthesis. The reagent has been used successfully for the N-protection of amino acids the bulky 1-adamantyloxycarbonyl group is removed by solvolysis with trifluoroacetic acid. The reagent was used also in the mixed-anhydride method of peptide synthesis, but considerable racemization was noted. 

The reagent has been used us hydrogen uhlorlde acceptor in the N-protection of amino acids by reaction with carbobanxoxy ehloridti ... 

N-Protective group. Zervas introduced use of the reagent for the N-protection of amino acid esters, including the activated p-nitrophenyl esters of use in peptide coupling. When required, the protective group is split by treatment with the theoretical amount of hydrogen chloride in alcohol. 

N-Protection of amino acids.1 The reagent reacts with an amino acid ester hydrochloride, for example that of glycine (4) in chloroform containing triethyl-... 

N-Protection of amino acids [before references]. For the preparation of N-f-butoxycarbonylamino acids, DeTar4 recommends use of 1 equivalent of the amino acid, 1.10 equivalents of the reagent, and 4 equivalents of tricthylamine. 

Peptide synthesisThe reagent is colorless and can be stored for over ten days in a deep freeze. It has been used as an alternative to carbobenzoxy chloride for the N-protection of amino acids. Condensation with an amino acid is carried out in chloroform in the presence of triethylamine. The blocking group is cleaved by trifluoroacetic acid or hydrogen chloride. 

N-Protection of amino acids. For the synthesis of /-butyloxycarbonyl-)3-benzyl-L-aspartic acid by the reaction of the amino acid derivative with /-butyl azidoformate, Polzhofer2 found that use of triethylamine as base gives a higher yield (75%) than use of magnesium oxide (40%). The yield using /-butyl 4-nitro-... 

This group was developed for the protection of amino acids. It is formed from 4-ethoxy-l,l,l-trifluoro-3-buten-2-one in aqueous sodium hydroxide (70-94% yield). Primary amino acids form the Z-enamines, whereas secondary amines such as proline form the -enamines. Deprotection is achieved with 1-6 N aqueous HCl in dioxane at rt. ... 

Synthesis Solid-phase. Polymerization of N-protected a-amino acids (Fmoc or Boc). Solid-phase sub-monomer synthesis... 

The Arndt-Eistert reaction (Scheme 2.1) which involves the Wolff rearrangement of diazoketones 13 (prepared from the corresponding commercially available N-protected-a-amino acids 12 by reaction of their mixed anhydrides with diazomethane a cautionary note is warranted here the generation and handling of diazomethane require special precautions) has been used extensively by Seebach and coworkers for the preparation of N-protected /9 -amino acids 14 and /9 -amino acid esters 15 and 16. 

P Maetz, M Rodriguez. A simple preparation of N-protected chiral a-aminonitriles from N-protected a-amino acids. Tetrahedron Lett 38, 4221, 1997. 

J Pless, RA Boissonnas. On the velocity of aminolysis of a variety of new activated N-protected a-amino-acid phenyl esters, in particular 2,4,5-trichlorophenyl esters. Helv Chim Acta 46, 1609, 1963. 

Enantioseparation Data for N-protected a-Amino Acids and Aryloxycarboxylic Acids on Butylcarbamates of Cs/Cg Stereoisomeric Cinchona Alkaloids... 

Intramolecular cyclization DKP formation through intramolecular cyclization of the Nj—C2 bond is an efficient route to ring closure and the construction of these head-to-tail dipeptides involves the coupling of an N-protected a-amino acid to an a-amino ester, followed by N-deprotection and cyclization. " ... 

NaHTe affords the selective carbalcoxy group dealkylation of C-protected and C- and N-protected a-amino acids. ... 

SCHEME 21. Synthesis of N-protected a-amino acids and aldehydes by stereoselective addition of bromohthioalkene 5 -41 to sulfonyhmines. Mukaiyama aldol reaction of a-aminoaldehydes... 

Synthesis of N-Protected a-Amino Acids from N-(Benzyloxycarbonyl)-L-Serine via Its g-Lactone N -(Benzyloxycarbonyl)-p-(Pyrazol-1-yl)-L-Alanine... 

Alternatively, oxazolones have been used as reagents to activate and to couple N-protected dicarboxylic amino acids wherein the carboxylate moiety acts as the nucleophile. For example, 2,4-dimethyl-5(4//)-oxazolone 255 reacts with N-benzyloxycarbonyl-L-aspartic acid to give a mixture of the anhydrides 256 and 257. Subsequent reaction of 256 and 257 with phenylalanine methyl ester hydrochloride and A-methylmorpholine produces a mixture of the a-isomer 258 and p-isomer 259 of Al-benzyloxycarbonyl-aspartylphenylalanine methyl ester (Scheme 7.83). °... 

This is particularly well illustrated by comparing the condensation reactions of three N-protected basic amino acids (Z-His, Z-Lys and Z-Arg) to Leu-NH2 [11]. In all three cases, the acyl donor is a zwitterion, but the ApKa values are very different... 

Among the methods described in Section 10.6.5, the syntheses reported by Umezawa et alJ78 and Garcfa-Lopez et al.179,80 have been most widely used. As summarized in Scheme 33, the synthesis is initiated with the preparation of a diazo ketone through the reaction between a N-protected a-amino acid and isobutyl chloroformate followed by treatment with diazomethane. The chloromethyl ketone is prepared by adding 2.5 M hydrochloric acid to the diazo ketone. Transhalogenation is exploited to obtain the iodomethyl ketone. Through in situ reaction with the sodium derivative of dimethyl malonate, the 4-oxo diester is obtained. 

To a cold soln (—15 °C) of the N -protected a-amino acid (lOmmol) in DME (10 mL) were successively added NMM (l.llmL, lOmmol) and isobutyl chloroformate (1.36mL, lOmmol). After lmin the precipitated NMM-HC1 was removed by filtration and washed with DME (5 x2mL). The filtrate and... 

Preparation of a (1-Amino Alcohol by Reduction of a N"-Protected a-Amino Acid General Proce-... 

A soln of the N -protected a-amino acid (10 mmol) in THF (10 mL) was added dropwise to a 0°C soln of 1M BH3-THF (20 mL, 20 mmol) under N2. The addition took place over a 30 min period, and the reaction was allowed to proceed for 1-2 h at 0°C. The reaction was quenched using 10% AcOH in MeOH (40 mL). After solvent evaporation the crude product was dissolved in EtOAc and washed with 1M HQ, H20, and 1M NH4HC03. The organic layer was dried (MgS04) and the product was recovered by removal of the solvent. 

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