2-Thiazolyl-0-alanine

McCague R, Taylor SJC. Integration of an acylase biotransforma-tion with process chemistry a one-pot synthesis of N-t-Boc-L-3-(4-thiazolyl)alanine and related amino acids. In Chirality in Industry n. Collins AN, Sheldrake GN, Crosby J, eds. 1997. John Wiley Sons, New York. pp. 184—206. 

A 5 L, 3-neck round bottom flask equipped with a mechanical stirrer was charged with the N-acetyl-3-(4-thiazolyl)-DL-alanine ethyl ester (210.0 g, 0.87 mol), distilled water (1.6 L), and 1 M aqueous KCI (0.8 L). The homogeneous solution was adjusted to pH 7.0 with 0.1 M NaOH and then was treated with Subtilisin Carlsberg (1.8 g) dissolved in 0.1 M aqueous KCI (25 ml). The reaction mixture was stirred at room temperature with 1.0 M NaOH added as required to maintain the pH at 6.25-7.25. After 4 h, 430 ml of base had been consumed and the reaction was judged to be complete. The reaction mixture was then extracted with chloroform (4x1.5 L), the aqueous phase was carefully acidified to pH 4 with 2 M HCI and then was concentrated under reduced pressure. Residual water was removed by consecutive evaporation... 

A 4 L Erlenmeyer flask equipped with a mechanical stirrer was charged with the 3-(4-thiazolyl)-L-alanine dihydrochloride (125.9 g) and tetrahydrofuran (1.5 L) and the mixture was adjusted to pH 6.6 with saturated aqueous sodium bicarbonate. The resultant solution was then adjusted to pH 8.9 with 3.0 M NaOH and a solution of di-tert-butyldicarbonate (117.8 g, 0.51 mol) in tetrahydrofuran (150 ml) was added. The reaction mixture was vigorously stirred at room temperature for 40 h. The tetrahydrofuran was removed under vacuum, the pH of the residue was adjusted to 2.0 with 3.0 M HCI and the mixture was extracted with ethyl acetate (3x300 ml). The combined extracts were dried over MgS04, filtered, and concentrated to give 150.0 g of a white solid. Recrystallization from hot 1 1 ethyl acetate/hexane (1.06 L) gave 107.6 g (82 %) of the desired N-boc-3-(4-thiazolyl)-L-alanine, melting point 115°C. 

They are easily prepared from dithiocarbamate and nickel(ll) salts, and examples including those derived from simple amines (587,1472) fluorinated amines (76) amines with (O-hydroxyl groups (1473) indole (341) indoline, carbazole, and imidazole (342) (72) together with those with heterocyclic (72,1116,1126,1424,1474) benzyl (346,1475) and aryl (95,1423,1425,1476, 1477) substituents. Others include examples prepared from Schiff bases (1121), 2-aryldecahydroquinolin-4-ones (1478), tetrahydroquinoline and tetrahydroiso-quinoline (1479), succinimide and phthalimide (49), l,4,7,10-tetraoxa-13-aza-cyclopetadecane (50), 1,3,4-thiazolyl (1426), and 3-dithiocarboxy-3-aza-5-aminopentanoate (343) (1480,1481). A wide range of amino acid derivatives have also been prepared (122,133-137), as have derivatives of glycine, DL-alanine and DL-valine peptide bonded to ethyl esters of a-amino acids (134). 

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