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J = 3.6, 3.6, 8.3 Hz, 1H), 2.36 (d, J = 2.3 Hz, 1H), 1.56 (q, J = 12.4 Hz, 1H), 1.34 (s, 6H), 1.31(s, 3H), 1.06 (s,
9H), 1.00 (s, 9H); 13C NMR (CDCl3, 100 MHz)
: 100.9, 100.4, 99.6, 99.3, 87.3, 85.6, 81.9, 77.2, 73.4, 72.8,
δ
70.6, 68.8, 68.7, 68.1, 67.1, 66.9, 66.7, 66.4, 59.9, 48.4, 48.1, 32.2, 27.4 (3C), 26.9 (3C), 22.7 (2C), 17.7, 17.6;
MS-API-ES: 865 [M + Na]+. HRMS (ESI+) calc for C32H54N12NaO13Si 865.35948, found 865.35965.
3.3.4. Synthesis of 5,20,3”-O-tri-Benzyl-20,30-O-(2,3-butanedione-bis-dimethyl-acetal)-4”,6”-O
-di-tert-butyl-silane-1,3,60,3”-tetra-azido-kanamycin A (11)
To a stirred solution of 10a (0.4 g, 0.38 mmol) and tetrabutylammonium iodide (51 mg, 0.14 mmol)
in dry DMF (1.9 mL) at 0 ◦C was added NaH (60% oil suspension, 0.1 g, 2.85 mmol). The obtained
mixture was stirred for 10 min at this temperature and then benzyl bromide (0.27 mL, 2.24 mmol)
was added dropwise. The reaction mixture was stirred overnight at room temperature and then
MeOH (1.5 mL) was added to quench. The solvent was eliminated under reduced pressure and the
residue was diluted with brine, and extracted with CH2Cl2 (2
dried over anhydrous Na2SO4, filtered and concentrated. Finally, the residue was purified by flash
chromatography on silica gel using hexane/AcOEt (95:5) to give 11 (0.28 g, 65%) as a white solid. H
×
25 mL). The organic phases were
1
NMR (CDCl3, 400 MHz)
δ 7.45–7.00 (m, 15H, Ar), 5.46 (d, J = 4.1 Hz, 1H), 5.22 (d, J = 3.6 Hz, 1H), 5.04
(d, J = 11.2 Hz, 1H), 4.81 (d, J = 12.1 Hz, 1H), 4,76 (d, J = 11.3 Hz, 1H), 4.66 (d, J = 11.2 Hz, 1H), 4.63(d, J
= 12.1 Hz, 1H), 4.36 (dd, J = 4.8, 2.4 Hz, 1H), 4.34 (d, J = 11.3 Hz, 1H), 4.14 (t, J = 10.1 Hz, 1H), 3.91 (dd,
J = 10.0, 5.0 Hz, 1H), 3.82 (dd, J = 10.2, 5.3 Hz, 1H), 3.80 (t, J = 9.4 Hz, 1H), 3.64 (dd, J = 10.0, 2.5 Hz,
1H), 3.61–3.56 (m, 1H), 3.55–3.53 (m, 1H), 3.50–3.45 (m, 2H), 3.44 (m, 1H), 3.38 (dd, J = 6.7, 3.8 Hz, 1H),
3.32–3.26 (m, 2H), 3.24 (s, 3H), 3.25 (s, 3H), 3.20–3.17 (m, 2H), 3.16 (dd, J = 10.3, 3.5 Hz, 1H), 2.40–2.38
(m, 1H), 1.65–1.51 (m, 1H), 1.29 (s, 6H), 1.02 (s, 9H), 0.89 (s, 9H). 13C NMR (CDCl3, 100 MHz)
δ: 138.4
(2C), 138.1, 129.2, 128.7 (2C), 128.4 (2C), 128.3 (2C), 128.1 (2C), 127.9 (2C), 127.7, 127.3, 126.4 (2C), 99.8,
99.6, 98.2, 97.4, 84.0, 81.4, 78.4, 77.1, 76.5, 74.4, 74.1, 73.9, 70.1, 69.4, 68.1, 67.6, 66.7, 64.7, 59.2, 50.6 (2C),
48.3, 48.2 (2C), 32.2, 31.7, 28.5, 27.6 (3C), 27.0 (3C), 22.8, 20.0. MS-API-ES: 1135 [M + Na]+. HRMS (ESI+)
calc for C53H72N12NaO13Si 1035.50033, found 1035.50102.
3.3.5. Synthesis of 5,20,3”-O-tri-Benzyl-4”,6”-O-di-tert-butyl-silane-1,3,60,3”-tetra-azido-kanamycin A (12)
To a solution of 11 (0.25 g, 0.22 mmol) in CH2Cl2 (2.3 mL) was added a mixture of TFA: H2O
(1 mL, 10:1 v/v). The mixture was stirred at room temperature for 40 min at room temperature and then,
a saturated aqueous solution of NaHCO3 was added and the mixture was extracted twice with AcOEt
(25 mL). The combined organic phases were dried over anhydrous Na2SO4, filtered and the solvent
was removed under reduced pressure. Finally, the residue was purified by flash chromatography on
1
silica gel using hexane/AcOEt (7:3) to give 12 (0.27 g, 85%) as a white foam. H NMR (CDCl3, 400
MHz)
δ 7.44–7.17 (m, 15H), 5.39 (d, J = 4.1 Hz, 1H), 5.34 (d, J = 3.4 Hz), 5.00 (d, J = 10.2 Hz, 1H), 4.93 (d,
J = 11.2 Hz, 1H), 4.82 (d, J = 10.2 Hz, 1H), 4.66 (d, J = 11.8 Hz, 1H), 4.59 (d, J = 11.2 Hz, 1H), 4.20 (ddd, J
= 9.9, 5.3, 2.4 Hz, 1H), 3.93–3.91 (m, 2H), 3.89 (m, 1H), 3.82 (dd, J = 9.8, 8.9 Hz, 1H), 3.69 (t, J = 9.4 Hz,
1H), 3.65 (m, 2H), 3.60 (m, 1H), 3.58 (ddd, J = 9.4, 5.6, 3.2 Hz, 1H), 3.55 (m, 1H), 3.49 (m, 1H), 3.42 (dd, J
= 13.3 Hz, 1H), 3.32 (ddd, J = 5.7, 3.0, 1.3 Hz, 1H), 3.28 (m, 1H), 2.24 (dt, J = 12.5, 4.0 Hz, 1H), 1.36 (q, J
= 12.5 Hz, 1H), 1.02 (s, 9H), 0.89 (s, 9H). 13C NMR (CDCl3, 100 MHz)
δ: 138.6, 138.5, 138.3, 128.3 (2C),
128.2 (2C), 128.1 (2C), 128.0 (2C), 127.9 (2C), 127.8, 127.5, 127.2 (2C), 127.1, 97.8, 97.5, 83.9, 78.7, 78.6, 77.0,
76.8, 74.5, 74.1, 73.8, 73.2, 72.2, 70.9, 67.6, 66.6, 64.9, 59.8, 59.6, 51.7, 46.8, 31.9, 26.7 (3C), 26.3 (3C), 22.3,
19.5. MS-API-ES: = 999 [M + H]+. HRMS (ESI+) calc for C47H63N12O11Si 999.45030, found 999.45168.
3.3.6. Synthesis of 1,3-di-Azido-5-O-benzyl-[(3-deoxy-3-azido-2-O-Benzyl-4,6-O-di-tert-butyl-silane)
-α-d-glucopyranosyl]-2-deoxy-streptamine (13)
To a well stirred solution of 12 (0.27 g, 0.27 mmol) in MeOH (8.8 mL) at 0 ◦C was added NaIO4
(0.1 g, 0. 52 mmol). The resulting suspension was stirred at this temperature for 24 h and then the
mixture was filtered through Celite®, which was washed with AcOEt. The mixture was concentrated
and the residue was dissolved in THF (6.6 mL) and treated with TEA (110 L, 0.79 mmol). The reaction
∝