BOC-GLY-GLY-GLY-OH

White to off-white powder

General procedure: Amino acid or peptide (1 mmol) was added with stirring to a solution of guanidine hydrochloride (15 molpercent) and di-tert-butyl dicarbonate (2.5-3 mmol) in EtOH (1 mL), at 35-40°C. The reaction mixture was continued to stir until a clear solution was obtained. EtOH was evaporated under vacuum and the residue was successively washed with water (2 mL) and hexane or petroleum ether (2 mL) to afford almost pure N-Boc amino acids or N-Boc peptides. If necessary, the crude products could be recrystallized for further purification.N-Boc-triglycine. Synthesis of GlyGlyGly-CPT 12 (0387) (0388) t-Boc-GlyGlyGly (1.359 g, 4.7 mmol) was dissolved in 350 mL of anhydrous methylene chloride at room temperature and to this solution were added DIPC (0.75 mL, 4.7 mmol), DMAP (382 mg, 3.13 mmol) and camptothecin (0.55 g, 1.57 mmol) at 0 C. The reaction mixture was allowed to warm to room temperature and left for 16 h. The solution was washed with 0.1 N HCl, dried and evaporated under reduced pressure to yield a white solid, which was recrystallized from methanol to give camptothecin-20-ester of t-Boc-GlyGlyGly: 1H NMR (DMSO-d6) delta 8.40 (s), 8.25 (d), 7.91 (d), 7.78 (m), 7.65 (t), 7.26 (s), 7.05 (br, s), 5.65 (d), 5.40 (d), 5.25 (s), 5.10 (br, s), 3.75-4.42 (m), 2.15-2.35 (m), 1.45 (s), 0.95 (t) Camptothecin-20-ester of t-Boc-GlyGlyGly (1.5 g, 1.06 mmol) was dissolved in a mixture of methylene chloride (10 mL) and TFA (10 mL) and stirred at room temperature for 1 h. Solvent was removed under vacuum and the residue was re-dissolved in methylene chloride. The solution was poured into ether to give instant precipitate (yellow). The precipitate was filtered and washed with cold ether to give 1.31 g of 12. 1H NMR (DMSO-d6) delta8.79 (s), 7.75-8.61 (m), 7.10 (s), 5.55 (s), 3.90-4.37 (m), 3.86 (s), 3.54 (s), 2.11-2.23 (m), 0.95 (t). ESI/MS (m/z) expected 519. Found 520 (M+H).The DMF (50 mL)solution of boc-Gly-Gly-Gly-OH (S1) (2.1 g, 7.4 mmol) and N-methylmorpholine(NMM) (0.76 mL, 7.0 mmol) was cooled to 0C, then isobutyl chloroformate (IBCF) (0.92 mL, 7.0 mmol) was slowly added.After the reaction at 0C for 20 min, 3-aminopyridine (0.66 g, 7.0 mmol) was added to the white suspended solution and then stirred at 0C for 1 h, and at room temperature for overnight. After the reacted solution was concentrated by evaporation, ethyl acetate (~30 mL) was added and light brown precipitate was filtered. The crude product was purified by SiO2 column chromatography (EtOAc / MeOH).The pale yellow solid S2 1.4 g was obtained. (Y 55%).M.p. 179-182 C; HR-MS: calcd. for [M+Na]+: 388.1591, found: 388.1603 (error 3.1 ppm); 1H NMR (500MHz, DMSO-d6, 300 K), delta10.03 (brs, 1H, PyNH), 8.77 (d, 2 Hz, 1H, PyH2), 8.27 (m, 2H, PyH6, Gly(3)NH), 8.20 (m, 1H, Gly(2)NH), 8.04 (d, 8.5 Hz, 1H, PyH4), 7.35 (dd, 4.5 Hz, 8 Hz, 1H, PyH5), 7.04 (t, 5.5 Hz, 1H, Gly(1)NH), 3.92 (d, 4.5 Hz, 1H, Gly(3)Halpha), 3.77 (d, 5.5 Hz, 1H, Gly(2)Halpha), 3.61 (d, 5.5 Hz, 1H, Gly(1)Halpha), 1.37(s, 9H, t-Bu); 13C NMR (125 MHz, DMSO-d6, 300 K), delta170.6 (Gly(1)CO), 169.8 (Gly(2)CO), 168.7 (Gly(3)CO), 156.3 (bocCO), 144.8 (PyC6), 141.3 (PyC2), 135.9 (PyC3), 126.6 (PyC4), 124.1 (PyC5), 78.6 (bocCq), 43.8(Gly(1)Calpha), 43.1 (Gly(3)Calpha), 42.6 (Gly(2)Calpha), 28.6 (bocCH3).

Molecular Weight:289.29
XLogP3:-0.8
Hydrogen Bond Donor Count:4
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:8
Exact Mass:289.12738533
Monoisotopic Mass:289.12738533
Topological Polar Surface Area:134
Heavy Atom Count:20
Complexity:388
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes