Compound 3
dispiro[adamantane-2,2'-[1,3,5]trioxolane-4',1''-cyclohexane]-3''-yl N-[(1S)-1-{[(2S,3S,4R,5R)-5-[6-(dimethylamino)-9H-purin-9-yl]-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl]carbamoyl}-2-(4-methoxyphenyl)ethyl]carbamate
From: A reactivity-based probe of the intracellular labile ferrous iron pool
Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.
A two-necked, 15-mL round-bottomed flask equipped with a stir bar, septa, and argon inlet was charged with puromycin dihydrochloride from Streptomyces alboniger (0.064 g, 0.1 mmol, 1.1 equiv.), 4-dimethylaminopyridine (ca. 0.002 g, 0.01 mmol, 0.15 equiv.), and 4-nitrophenyl carbonate 12 (0.048 g, 0.1 mmol, 1.0 equiv.) and the atmosphere was replaced with argon. This material was then dissolved in N,N-dimethylformamide (4 mL) and N,N-diisopropylethylamine (0.10 ml, 0.6 mmol, 5.3 equiv.) was added to this solution. The reaction mixture was allowed to stir at room temperature under argon for 5 hours then diluted with 10 mL of EtOAc and washed with four, 15-mL portions of sat. NaHCO3. The aqueous layer was back extracted with 20mL of EtOAc and the organic layers were combined, washed with 20 mL of satd aq NaCl solution, and then dried over MgSO4, filtered, and concentrated to afford a light yellow oil. Purification via column chromatography on 25 g of silica gel (gradient elution with 0-10% MeOH/CH2Cl2) afforded the desired material with minor impurities. Further purification via reverse phase chromatography on a Silicycle 12 g C-18 column with gradient elution 0-100% MeOH/H2O with constant 0.05% formic acid yielded 65 mg (78%) of 3 as a white solid (>95% purity by HPLC). 1H NMR (400MHz, CD3OD): δ = 7.70–7.80 (m, 2 H), 6.68 (d, J=8.6 Hz, 2 H), 6.39 (dd, J=8.6, 1.5 Hz, 2 H), 6.11 (d, J=7.5 Hz, 1 H), 5.30–5.34 (m, 1 H), 4.15 (s, 3 H), 4.06–4.12 (m, 1 H), 3.99–4.05 (m, 1 H), 3.83–3.92 (m, 1 H), 3.51 (br. s., 1 H), 3.40 (d, J=12.8 Hz, 1 H), 3.13 (d, J=12.5 Hz, 1 H), 3.03 (br. s., 6 H), 2.85–2.88 (m, 1 H), 2.40–2.55 (m, 2 H), 1.69 - 1.78 (m, 1 H), 1.07–1.56 (m, 19 H), 0.89–1.04 (m, 1 H), 0.72–0.87 ppm (m, 2 H); 13C NMR (100MHz, CD3OD): δ = 191.2, 173.6, 159.4, 156.8, 155.6, 152.4, 149.6, 138.5, 131.0, 129.4, 125.9, 121.4, 114.7, 112.3, 109.4, 91.6, 84.7, 74.3, 72.3, 62.0, 59.9, 55.7, 52.4, 51.3, 51.3, 40.9, 39.1, 38.3, 37.4, 37.1, 37.0, 35.4, 34.3, 31.2, 27.6, 27.2, 20.4 ppm; HRMS (ESI) m/z [M+H]+ calcd for C39H51N7O10: 778.3776; found: 778.3786.
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313573306
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