Methanol → L-Isoleucine

Participants

Reaction Conditions

Reaction Steps

The acid obtained above was coupled with the hydrochloride salt of tubuphenylalanine (Tup) methyl ester (22.5 mg, 0.09 mmol) following the DIC/PFP protocol in a similar way as described for the synthesis of compound 5 to give after reverse phase HPLC purification the peptoid 9 (8.0 mg, 9.8 μmol). HRMS calculated for C44H67N6O7S [M+H]+: 823.4795. found: 823.4789. Subsequently, the obtained oil was dissolved in a commercially available 4 N solution of HCl in dioxane (2 mL) and the mixture was stirred for 1 h. Afterward, MeOH (2 mL) was added and the stirring was continued for an additional 3 h. (The hydrolysis of the convertible Ugi-Armstrong-amides alternatively can also be performed on the stage of intermediates like 8 etc.). The solvent was removed under reduced pressure and the residue was dissolved in pyridine (4.0 mL) and the solution was cooled to 0° C. Acetic anhydride (84 μL, 0.90 mmol) was added and the reaction was stirred overnight and allowed to reach gradually rt. The solvent was removed under reduced pressure and the crude mixture submitted to reverse phase HPLC purification to render 6.3 mg of tubugi H (7.9 μmol, 4.0% yield overall). 1H-NMR (599.8 MHz, CD3OD, representative signals): δ=0.79 (d, 3H, J=6.6 Hz), 0.90 (t, 3H, J=7.4 Hz), 0.98 (d, 3H, J=7.0 Hz), 1.01 (d, 3H, J=6.6 Hz), 1.14 (d, 3H, J=7.4 Hz), 1.18-1.23 (m, 1H), 1.38 (m, 1H), 2.16 (s, 3H), 2.41 (s, 3H), 3.59 (s, 3H), 3.61 (s, 3H), 3.63 (d, 1H), 4.35 (m, 1H), 4.42 (d, 1H, J=9.9 Hz), 4.58 (br m, 1H), 4.83 (overlap signal), 6.32 (dd, 1H, J=11.6/1.9 Hz), 7.16 (m, 1H), 7.21 (m, 4H), 8.01 (s, 1H) ppm. HRMS calculated for C41H62N5O9S [M+H]+: 800.4277. found: 800.4280.

Provenance & Evidence