Protection a-aminocarboxylic acid

N-Protected a-aminocarboxylic acid amides. A soln. of N-(4-methoxybenzyloxycar-bonyl)alanine in 4 1 dichloromethane/dimethylformamide treated with 1-hydroxy-benzotriazole and dicyclohexylcarbodiimide, stirred for 30 min, 25% aq. NH3 added, and stirred for 3-5 h until reaction complete (t.l.c.) - N-(4-methoxybenzyloxycar-bonyl)alanine amide. Y 83%. The method is high-yielding and racemization-free. F.e. inch Boc- and Cbz-aminoacid and dipeptide derivs. s. S.-T. Chen et al.. Synthesis 1989, 37-8 with 2-ethoxy-N-ethoxycarbonyl-l,2-dihydroquinoline and NH4HCO3 cf. S. Nozaki, I. Muramatsu, Bull. Chem. Soc. Japan 61, 2647-8 (1988). 

N-Protected a-aminocarboxylic acid pentafluorophenyl esters from their acids... 

Thionyl chloride acetic anhydride Protection of a-aminocarboxylic acid groups as 5-oxazolidones... 

Peptide formation with an A-protected, optically pure aminocarboxylic acid is an alternative means of obtaining diastereoisomeric derivatives of chiral aminoalkylphos-phonic acids, the diastereoisomeric products being distinguishable on a quantitative basis by P NMR spectroscopy for example, A-boc-L-alanine was used to distinguish the enantiomers of diethyl (a-aminobenzyl)phosphonate. The reaction between an enan-tiomerically enriched sample of 125 (R = H) and L-leucine methyl ester hydrochloride in the presence of DCC was followed by HPLC separation of the l,l- and D,L-peptides 126 (R = H ratio 95.3 4.7), and essentially the same procedure was applied to an analysis of 125 (R = OCH2Ph), as prepared using the bislactim ether procedure (see Section IV. C.2.b) when the final product consisted of a mixture of R,S and S,S diastereoisomers in the ratio 87.4 12.6 ... 

The reactions of phosphorous acid are paralleled still further by the additions of hypophosphorus acid to azomethines in practice, mixtures of amines and carbonyl reactants may be employed ", but the drawbacks to the procedure found for the synthesis of aminoalkylphosphonic acids may well apply here also. In a valuable publication, Dingwall and coworkers described the syntheses of (aminoalkyl)phosphinic acid analogues of many of the naturally occurring aminocarboxylic acids by the simple treatment of the benzyhydrylimine derivatives of the necessary amines with hypophosphorous acid, formed in situ when diphenylmethylammonium hypophosphite is treated with an appropriate aldehyde this step is followed by removal of the A -protection with 48% aqueous HBr, with 18% aqueous HCl or with trifluoroacetic acid in boiling methoxybenzene any second amino group was protected as the phthalimido derivative. 

In principle, the reactions employed to bring about peptide formation between an (aminoalkyl)phosphonic acid and an aminocarboxylic acid are similar to those used in conventional peptide chemistry. Thus, a diester of the (aminoalkyl)phosphonic acid is brought into contact with the A-protected aminocarboxylic acid in the presence of dicy-clohexylcarbodiimide (Scheme 60) or the carboxylic acid may be activated by preliminary reaction (mixed anhydride formation) with an appropriate reagent, e.g. Bu COCl , ClCOOEt or ClCOOCHMeEt , or by the use of A-hydroxysuccinimide The... 

By these various procedures block copolypeptides have been obtained with different combinations of crystalline, glassy or elastomeric, or hydrophilic and hydrophobic segments. In some cases, a sensitive group of the aminocarboxylic acid component has to be protected during the... 

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