(2,5-dioxopyrrolidin-1-yl) (2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-phenylpropanoate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of Lys(Mtr) 2 (4.686 g, 11.20 mmol) and NaHCO3 (941.0 mg, 1 equiv) in water (100 mL) and DME (50 mL) was treated with a solution of Fmoc-Phe-OSu 7a (11.20 mmol) in DME (50 mL). THF (25 mL) was then added to aid solubility. The mixture was stirred at rt for 2 days and then as much DME as possible was removed on the rotovap (bath at 30° C.). The resulting gummy suspension was partitioned between ethyl acetate and pH 5 buffer. The organic phase was washed with water and brine, dried and evaporated to give a pale yellow foam. This was flushed with methylene chloride (100 mL). TLC showed the product to be satisfactorily pure and it was carried on without further purification (8.559 g, 97%). 1H-NMR (CDCl3/CD3OD) δ 1.10-1.93 (m, 6H), 2.31 (t, 2H), 3.00 (m, 2H), 3.71 (s, 3H), 4.02-4.48 (m, 5H), 6.79 (d, 2H), 7.00-7.75 (m, 25H). MS (FAB) 788.2 (MH)+, 810.4 (M+Na)+, 826 (M+K)+. Anal. Calcd for C50H49N3O6—H2O: C-74.51, H-6.38, N-5.21. Found: C-74.17, H-6.57, N-5.41. as much DME as possible was removed on the rotovap (bath at 30° C.) The resulting gummy suspension was partitioned between ethyl acetate and pH 5 buffer The organic phase was washed with water and brine dried evaporated to give a pale yellow foam This was flushed with methylene chloride (100 mL) it was carried on without further purification (8.559 g, 97%)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred suspension of Fmoc-Phe-OSu (2.0702 g, 4.2728 mmol, 1.0 eq) and Lys(MMT) (1.7995 g, 4.2995 mmol, 1.01 eq) in DMF (30 ml) was added DIEA (1.5 ml, 8.6112 mmol, 2.02 eq). The solid dissolved gradually and the solution was stirred at room temperature overnight. The reaction mixture was partitioned between ethyl acetate (100 ml) and pH5 buffer (0.05M phthalic acid, adjusted with 10N KOH to pH 5.0, 200 ml). The aqueous solution was extracted with more ethyl acetate (50 ml×2). The combined organic phase was washed with brine (50 ml×3), dried over MgSO4. After removal of solvent and being dried in vacuo, 3.3014 g (98.1%) of pale-yellow foam was obtained. ES(+)-MS: 516(M-MMT+1), 273(MMT). The solid dissolved gradually The reaction mixture was partitioned between ethyl acetate (100 ml) and pH5 buffer (0.05M phthalic acid, adjusted with 10N KOH to pH 5.0, 200 ml) The aqueous solution was extracted with more ethyl acetate (50 ml×2) The combined organic phase was washed with brine (50 ml×3) dried over MgSO4 After removal of solvent being dried in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of Fmoc-Phe (1.9442 g, 5.0186 mmol, 1.0 eq) and N-hydroxysuccinimide (0.6095 g, 5.2959 mmol, 1.06 eq) in methylene chloride (50 ml) cooled in an ice bath, was added DCC (1.0880 g, 5.2731 mmol, 1.05 eq). The mixture was stirred at room temperature overnight. The resulting DCU was removed by filtration and the filtrate was condensed and dried in vacuo to give 2.7664 g of white foam. cooled in an ice bath The resulting DCU was removed by filtration condensed dried in vacuo