Y-Aminocarboxylic acids

The importance of four-membered heterocycles for organic synthesis is limited. Examples are the alkene synthesis involving oxetan-2-ones and the y -aminocarboxylic acid synthesis involving azetidin-2-ones. 

Retention of configuration s. 19, 17 y-Aminocarboxylic acids from 4-nitro-2-thiopbenecarboxylic acids... 

The reaction of amino acid imidazolides with the potassium salt of monomethyl malonate in the presence of one equivalent of MgCl2, CoCl2, or MnCl2 results in the formation of jS"keto-y-aminocarboxylates.[64]... 

Another synthesis of jS-keto-y-aminocarboxylates starts from TV-protected amino-acid imidazolides and magnesium p-nitrobenzyl malonate (50-60 °C, about 6h).[65]... 

The reaction can be used to prepare five-, six-, and seven-membered lactams from y, S, and oj-aminocarboxylic acids. 

Andronova, I.G., Maleev. V.L, Ragulin, V.V., Il in, M.M.. Tsvetkov, E.N., and Belokon, Y.N., Phosphorus-containing aminocarboxylic acids. Part 7. Asymmetric synthesis of ro-phosphono-a-aminocar-boxylic acids, Zh. Obshch. Khim., 66,1096, 1996 Russ. J. Gen. Chem. (Engl. Transl.), 66,1068,1996. 

Aminophosphinic acid esters. NaNHg added at -33° with stirring to ethyl benzylpropylphosphinate and N-benzylidene-p-toluidine in abs. ether, and after 4 hrs. treated with 7%-HCl at the same temp. -> ethyl (2-p-toluidino-l,2-diphenyl-ethyl)propylphosphinate. Y 81%. F. e. s. M. Kirilov, J. Petrova, and K. PetkanSin, B. 104, 173 (1971) -aminocarboxylic acids s. A. Dobrev and C. Ivanov, B. 104, 981. 

By using active peptide esters with high molecular ester components, inter-molecular aminolysis can be suppressed. — E Glycyl glycine cross-linked poly-(4-hydroxy-3-nitrostyrene) ester hydrobromide suspended in dimethylformamide, neutralized with triethylamine, allowed to stand 12 hrs. at room temp., and the resulting poly-4-hydroxy-3-nitrostyrene removed by filtration diketo-piperazine. Y 75%. F. e. and ester components s. M. Fridkin, A. Patchornik, and E. Katchalski, Am. Soc. 87, 4646 (1965) peptides s. T. Wieland and G. Birr, Ang. Gh. 78, 303 (1966) with active a-aminocarboxylic acid polyphenolesters s. M. Fridkin, A. Patchornik, and E. Katchalski, Am. Soc, 88, 3164 (1966). 

Startg. 2,3-azetidinedione added to ca. 1.4 eqs. m-chloroperoxybenzoic acid in methylene chloride at — 20°, the mixture stirred for 60 min, treated dropwise with a soln. of / r/-butylamine and pyridine in the same solvent, and stirred at room temp, for 70 min product. Y 70%. F.e. and a-aminocarboxylic acid esters with alcohols, also 3-(a-nitroalkylidene)-2-azetidinones, s. F.P. Cossio et al., Tetrahedron Letters 29, 3133-6 (1988). 

A soln. of startg. chiral lactone in abs. ethanol treated with N-cyclohexylhydroxyl-amine at room temp, for 3 h, the solvent removed, the mixture chromatographed, and the adduct silylated by standard procedure - (3S)-product. Y 73%. The products are readily converted to chiral P-aminocarboxylic acids. F.e.s. I. Panfil et al.. Tetrahedron Letters 30, 1527-8 (1989). 

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). 

Thioketocarboxylic acid esters from a,y -ethylene-) -aminocarboxylic acid esters ... 

A soln. of alanine in 2 iV NaOH warmed 5 min. with a-acetyl- -ethoxy-N-ethoxy-carbonylacrylamide 5-acetyluracil-l-a-methylacetic acid. Y 75-100%.—The products are useful derivatives of a-aminocarboxylic acids. They are immune to hydrolysis by strong acids and may be used for the determination of N-terminal moieties in proteins. F. e., also from peptides and proteins, s. J. H. Dewar and G. Shaw, Soc. 1961, 3254. 

Phenylacetic acid allowed to react with Li-diisopropylamide in hexamethylphos-phoramide-tetrahydrofuran-hexane, then treated 2 hrs. at -15° with 0-methyl-hydroxylamine a-phenylglycine. Y 55.5%. - This is the first method reported for the direct conversion of carboxylic to a-aminocarboxylic acids. - Other aminating agents (s. original) gave lower yields. S. Yamada, T. Oguri, and T. Shioiri, Chem. Commun. 1972, 623. 

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