3-Hydroxy-2,2-dimethylpropionic acid → 3-hydroxy-2,2-dimethyl-N-(4-(4-(2-methyl-5-((2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(methylthio)tetrahydro-2H-pyran-2-yl)benzyl)phenyl)butyl)propanamide

Participants

Reaction Steps

To a solution of (2S,3S,4R,5S,6R)-2-(3-(4-(4-aminobutyl)benzyl)-4-methylphenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triyl triacetate (19, 55 mg, 0.10 mmol), 3-hydroxy-2,2-dimethylpropanoic acid (18 mg, 0.15 mmol), HATU (57 mg, 0.15 mmol), and DIPEA (52 μL, 0.30 mmol) were combined in DMF (1 mL) and stirred for 4 hours at room temperature. The reaction quenched with saturated aqueous NaHCO3 and extracted twice with EtOAc. The combined organic layers were washed with brine, dried with MgSO4, filtered, and concentrated under vacuum. The residue was dissolved in MeOH and treated with a few drops of NaOMe (25 wt % in MeOH) for 1 hour. The reaction was concentrated under vacuum, and the residue was purified by prep HPLC (C18 30×100 mm column, 5-40% CH3CN/10 mM aqueous ammonium formate, 45 mL/min) to give the title compound 21 as a white solid (22 mg, 41% yield). 1H NMR (400 MHz, MeOH-d4) δ ppm 6.98-7.22 (m, 7 H), 4.39 (d, J=9.6 Hz, 1 H), 4.13 (d, J=9.1 Hz, 1 H), 3.90-3.99 (m, 2 H), 3.49 (s, 2 H), 3.35-3.46 (m, 3 H), 3.19 (t, J=6.9 Hz, 2 H), 2.58 (t, J=7.5 Hz, 2 H), 2.18-2.23 (m, 3 H), 2.14 (s, 3 H), 1.60 (s, 2 H), 1.46-1.57 (m, 2 H), 1.11 (s, 6 H). MS (ES+) [M+H]+=532.

Provenance & Evidence