Reaction Steps
Synthesis of methyl [(3S,5S,7S)-7-{(1E,3E)-5-[(2S,3S,5R,6R)-5-{[(2Z,4S)-4-hydroxypent-2-enoyl]amino}-3,6-dimethyltetrahydro-2H-pyran-2-yl]-3-methylpenta-1,3-dien-1-yl}-1,6-dioxaspiro[2.5]oct-5-yl]acetate (#B148). To a solution of the crude material from Step 1 of example A#50 in methanol (3.5 mL) at rt was added potassium carbonate (136 mg, 0.056 mmol, 2.5 eq.), and the reaction was stirred for 2 hours. The reaction was filtered with methanol, diluted with dimethyl sulfoxide (2 mL), and concentrated in vacuo. Purification by reverse phase medium pressure liquid chromatography eluted with 0.02% acetic acid in water (v/v) and 0.02% acetic acid in acetonitrile (v/v) (10% to 90%) provided #B148 as a white solid. Yield: 91.6 mg, 0.18 mmol, 48%. LCMS (Protocol D): m/z 492.47 [M+H]+, retention time=0.80 minutes. 1H NMR (400 MHz, DMSO-d6) δ 7.76 (d, J=7.8 Hz, 1H), 6.25 (d, J=16.0 Hz, 1H), 5.97 (d, J=11.9 Hz, 1H), 5.87 (d, J=11.9 and 7.0 Hz, 1H), 5.65-5.48 (m, 2H), 5.22-5.13 (m, 1H), 5.10 (d, J=4.7 Hz, 1H), 4.56-4.48 (m, 1H), 4.36-4.25 (m, 1H), 3.69-3.61 (m, 2H), 3.60 (s, 3H), 3.55-3.46 (m, 1H), 2.74-2.56 (m, 4H), 2.38-2.13 (m, 2H), 1.90-1.60 (m, 9H), 1.44 (dd, J=13.2 and 7.0 Hz, 1H), 1.11 (d, J=6.2 Hz, 3H), 1.06 (d, J=6.2 Hz, 3H), 0.96 (d, J=7.0 Hz, 3H).
