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Z. M. Ištuk et al. / Bioorg. Med. Chem. 19 (2011) 556–566
1.17 (7-Hb), 1.01 (4-CH3), 1.05 (8-CH3), 0.91 (15-H). 13C NMR
(125 MHz, CDCl3) [d/ppm] isopropyl: 47.5 (CH), 23.6 (2 ꢁ CH3);
macrolide: 174.7 (C-1), 154.0 (C@N), 106.4 (C-10), 93.8 (C-5), 81.5
(C-11), 78.2 (C-3), 75.3 (C-13), 74.5 (C-6), 71.8 (C-12), 70.3 (C-20),
70.2 (C-50), 65.5 (C-30), 60.3 (C-10), 50.6 (C-9), 44.7 (C-2), 36.8 (4-
C), 36.1 (C-7), 40.2 (30-N(CH3)2), 27.9 (C-40), 25.9 (6-CH3), 24.5 (8-
C), 20.6 (8-CH3), 20.5 (C-14), 21.1 (50-CH3), 16.0 (2-CH3), 10.2 (C-
15), 15.8 (12-CH3), 19.3 (10-CH3), 7.7 (4-CH3). HRMS (ES) calcd
for C33 H61N3O9 (M+H+) 644.4481, found 644.4455.
4.22. 9a,11-O-[N0-(1-Naphtyl)carbonimidoyl]-6-O-methyl-9-
deoxo-9a-aza-9a-homoerythromycin A (30)
According to the general procedure, reaction of 300 mg of 2
(0.40 mmol) and 1-naphtyl isothiocyanate afforded 30 (163 mg,
44%) as a white foam. IR (KBr) [m
/cmꢀ1]: 3451, 2972, 2937, 2831,
2786, 1738, 1675, 1573, 1505, 1461, 1387, 1252, 1164, 1112,
1053, 1001, 941, 891, 834, 795, 777, 719, 673, 639. 1H NMR
(500 MHz, CDCl3) [d/ppm] naphtyl: 8.38 (CH), 7.53 (CH), 7.44
(CH), 7.44 (2 ꢁ CH), 7.39 (2 ꢁ CH); macrolide: 5.02 (13-H), 4.98
(100-H), 4.51 (10-H), 4.25 (11-H), 4.07 (500-H), 3.95 (5-H), 3.84 (3-
H), 3.68 (9-Ha), 3.54 (10-H), 3.52 (50-H), 3.32 (300-OCH3), 3.22 (6-
OCH3), 3.22 (20-H), 3.03 (400-H), 2.98 (2-H), 2.57 (8-H), 2.45 (30-H),
2.39 (9-Hb), 2.35 (200-Ha), 2.00 (30-N(CH3)2), 2.22 (4-H), 1.81 (14-
Ha), 1.67 (40-Ha), 2.31 (7-Ha), 1.62 (200-Hb), 1.47 (14-Hb), 1.42 (7-
Hb), 1.33 (6-CH3), 1.29 (500-CH3), 1.31 (2-CH3), 1.26 (40-Hb), 1.26
(300-CH3), 1.22 (10-CH3), 1.21 (50-CH3), 1.17 (12-CH3), 1.10 (4-
CH3), 0.97 (8-CH3), 0.82 (15-H). 13C NMR (125 MHz, DMSO) [d/
ppm] naphtyl: 144.4 (C), 134.2 (C), 129.7 (C), 127.4 (CH), 126.5
(CH), 125.2 (CH), 124.7 (CH), 124.3 (CH), 120.9 (CH), 118.5 (CH);
macrolide: 174.1 (C-1), 149.8 (C@N), 102.3 (C-10), 96.7 (C-100),
80.0 (C-3), 79.7 (C-5), 79.8 (C-11), 78.7 (C-6), 77.9 (C-400), 75.8 (C-
13), 72.9 (C-300), 71.9 (C-12), 71.2 (C-20), 68.5 (C-50), 66.2 (C-500),
65.6 (C-30), 58.0 (C-10), 51.7 (6-OCH3), 50.6 (C-9), 49.4 (300-OCH3),
44.8 (C-2), 40.4 (30-N(CH3)2), 38.0 (4-C), 36.5 (C-7), 35.7 (200-C),
28.8 (C-40), 25.5 (8-C), 21.5 (50-CH3), 20.8 (300-CH3), 20.7 (8-CH3),
20.4 (C-14), 20.8 (6-CH3), 18.7 (500-CH3), 17.0 (2-CH3), 15.3 (12-
CH3), 13.7 (10-CH3), 9.6 (4-CH3), 10.4 (C-15). HRMS (ES) calcd for
C49 H77N3O12 (M+H+) 900.5586, found 900.5147
4.20. 9a,11-O-[N0-(1-Naphtyl)carbonimidoyl]-9-deoxo-9a-aza-
9a-homoerythromycin A (28)
According to the general procedure, reaction of 300 mg of 1
(0.41 mmol) and 1-naphtyl isothiocyanate afforded 28 (67 mg,
18%) as a white foam. IR (KBr) [m
/cmꢀ1]: 3571, 3452, 2970, 2931,
1739, 1674, 1573, 1505, 1461, 1388, 1253, 1165, 1111, 1052,
1001, 961, 895, 796, 721, 672. 1H NMR (500 MHz, CDCl3) [d/ppm]
naphtyl: 8.37 (CH), 7.76 (CH), 7.46 (2 ꢁ CH), 7.43 (2 ꢁ CH), 7.40
(CH); macrolide: 5.00 (13-H), 4.96 (100-H), 4.45 (10-H), 4.33 (11-
H), 4.20 (3-H), 4.06 (500-H), 3.72 (9-Ha), 3.68 (5-H), 3.59 (10-H),
3.51 (50-H), 3.31 (300-OCH3), 3.26 (20-H), 3.00 (400-H), 2.95 (2-H),
2.51 (8-H), 2.48 (30-H), 2.48 (9-Hb), 2.36 (200-Ha), 2.34 (30-
N(CH3)2), 2.17 (4-H), 1.79 (14-Ha), 1.69 (40-Ha), 1.57 (7-Ha), 1.60
(200-Hb), 1.47 (14-Hb), 1.44 (7-Hb), 1.35 (6-CH3), 1.28 (500-CH3),
1.28 (2-CH3), 1.26 (40-Hb), 11.24 (10-CH3), 1.23 (300-CH3), 1.23
(50-CH3), 1.16 (12-CH3), 1.13 (4-CH3), 1.02 (8-CH3), 0.82 (15-H).
13C NMR (125 MHz, CDCl3) [d/ppm] naphtyl: 143.9 (C), 134.2
(C), 129.6 (C), 127.5 (CH), 126.8 (CH), 125.2 (CH), 124.4
(2 ꢁ CH), 121.2 (CH), 118.5 (CH); macrolide: 174.1 (C-1), 150.0
(C@N), 103.0 (C-10), 96.7 (C-100), 84.3 (C-5), 80.8 (C-3), 80.0 (C-
11), 77.9 (C-400), 75.7 (C-13), 75.3 (C-6), 72.7 (C-300), 71.9 (C-12),
71.1 (C-20), 68.7 (C-50), 65.8 (C-500), 65.7 (C-30), 58.1 (C-10), 50.4
(C-9), 49.4 (300-OCH3), 44.8 (C-2), 40.4 (30-N(CH3)2), 38.8 (4-C),
36.8 (C-7), 35.3 (200-C), 28.9 (C-40), 27.4 (6-CH3), 25.3 (8-C), 21.5
(300-CH3), 21.0 (8-CH3), 20.4 (C-14), 21.4 (50-CH3), 18.7 (500-CH3),
16.8 (2-CH3), 15.2 (12-CH3), 13.6 (10-CH3), 9.5 (4-CH3), 10.4 (C-
15). HRMS (ES) calcd for C45 H75N3O12 (M+H+) 886.5424, found
886.5388.
4.23. 9a,11-O-[N0-(1-Naphtyl)carbonimidoyl]-3-decladinosyl-6-
O-methyl-9-deoxo-9a-aza-9a-homoerythromycin A (31)
According to the general procedure, reaction of 300 mg of 4
(0.51 mmol) and 1-naphtyl isothiocyanate afforded 31 (67 mg,
17%) as a white foam. IR (KBr) [m
/cmꢀ1]: 3442, 3044, 2972, 2936,
2877, 2832, 2787, 1736, 1674, 1572, 1505, 1459, 1388, 1298,
1252, 1213, 1162, 1114, 1077, 1050, 980, 940, 891, 796, 777,
724, 672. 1H NMR (500 MHz, CDCl3) [d/ppm] naphtyl: 8.41 (CH),
7.49 (CH), 7.45 (CH), 7.45 (2 ꢁ CH), 7.39 (2 ꢁ CH); macrolide: 5.09
(13-H), 4.49 (10-H), 4.33 (11-H), 3.77 (5-H), 3.72 (9-Ha), 3.68
(3-H), 3.51 (50-H), 3.49 (10-H), 3.26 (20-H), 3.00 (6-OCH3), 2.67
(8-H), 2.63 (2-H), 2.47 (30-H), 2.45 (4-H), 2.37 (9-Hb), 2.25
(30-N(CH3)2), 1.84 (14-Ha), 1.64 (40-Ha), 1.55 (7-Ha), 1.49 (14-Hb),
1.35 (2-CH3), 1.28 (6-CH3), 1.25 (40-Hb), 1.23 (7-Hb), 1.28
(10-CH3), 1.24 (12-CH3), 1.23 (50-CH3), 1.08 (4-CH3), 0.97 (8-CH3),
0.84 (15-H). 13C NMR (125 MHz, CDCl3) [d/ppm] naphtyl: 144.5
(C), 134.7 (C), 130.2 (C), 127.8 (CH), 126.7 (CH), 125.6 (CH), 125.1
(CH), 124.7 (CH), 121.3 (CH), 118.6 (CH); macrolide: 174.9 (C-1),
149.7 (C@N), 107.3 (C-10), 89.7 (C-5), 79.9 (C-11), 79.4 (C-3), 78.7
(C-6), 76.1 (C-13), 72.2 (C-12), 71.0 (C-50), 70.5 (C-20), 66.2 (C-30),
58.8 (C-10), 51.1 (C-9), 50.7 (6-OCH3), 45.2 (C-2), 40.6
(30-N(CH3)2), 37.0 (C-7), 35.9 (4-C), 28.9 (C-40), 25.4 (8-C), 21.6
(50-CH3), 21.0 (C-14), 20.8 (8-CH3), 19.9 (6-CH3), 16.4 (2-CH3),
15.9 (12-CH3), 14.2 (10-CH3), 10.7 (C-15), 8.3 (4-CH3). HRMS (ES)
calcd for C41 H63N3O9 (M+H+) 742.4643, found 742.4650.
4.21. 9a,11-O-[N0-(1-Naphtyl)carbonimidoyl]-3-decladinosyl-9-
deoxo-9a-aza-9a-homoerythromycin A (29)
According to the general procedure, reaction of 300 mg of 3
(0.52 mmol) and 1-naphtyl isothiocyanate afforded 29 (193 mg,
51%) as a white solid. IR (KBr) [m
/cmꢀ1]: 3451, 2936, 1738, 1674,
1573, 1505, 1458, 1388, 1300, 1253, 1215, 1163, 1112, 1073,
1047, 980, 945, 894, 796, 777, 723, 673. 1H NMR (500 MHz, CDCl3)
[d/ppm] naphtyl: 8.33 (CH), 7.75 (CH), 7.48 (2 ꢁ CH), 7.41 (CH),
7.48 (2 ꢁ CH); macrolide: 5.06 (13-H), 4.45 (10-H), 4.35 (11-H),
3.82 (3-H), 3.77 (9-Ha), 3.60 (5-H), 3.53 (50-H), 3.51 (10-H), 3.28
(20-H), 2.62 (2-H), 2.59 (8-H), 2.52 (30-H), 2.45 (9-Hb), 2.28 (30-
N(CH3)2), 2.38 (4-H), 1.80 (14-Ha), 1.68 (7-Ha), 1.66 (40-Ha), 1.48
(14-Hb), 1.36 (2-CH3), 1.27 (7-Hb), 1.27 (10-CH3), 1.26 (40-Hb),
1.26 (6-CH3), 1.23 (50-CH3), 1.20 (12-CH3), 1.08 (4-CH3), 1.04 (8-
CH3), 0.84 (15-H). 13C NMR (125 MHz, CDCl3) [d/ppm] naphtyl:
143.6 (C), 134.2 (C), 129.7 (C), 127.5 (CH), 126.8 (CH), 125.3 (CH),
124.3 (2 ꢁ CH), 121.4 (CH), 118.5 (CH); macrolide: 174.5(C-1),
150.2 (C@N), 106.5 (C-10), 93.7 (C-5), 80.0 (C-11), 78.5 (C-3), 74.6
(C-6), 75.4 (C-13), 71.9 (C-12), 70.4 (C-20), 70.1 (C-50), 65.7 (C-30),
58.5 (C-10), 50.6 (C-9), 44.7 (C-2), 36.8 (4-C), 36.9 (C-7), 40.2 (30-
N(CH3)2), 28.2 (C-40), 26.1 (6-CH3), 25.2 (8-C), 20.7 (8-CH3), 20.5
(C-14), 21.2 (50-CH3), 16.1 (2-CH3), 15.3 (12-CH3), 13.6 (10-CH3),
10.4 (C-15), 7.8 (4-CH3). HRMS (ES) calcd for C45 H75N3O12
(M+H+) 728.4481, found 728.4471.
4.24. 9a,11-O-{N0-[4-(3-Methoxy)biphenyl]carbonimidoyl}-9-
deoxo-9a-aza-9a-homoerythromycin A (32)
According to the general procedure, reaction of 250 mg of 1
(0.34 mmol) and 3-(2-methoxy)biphenyl isothiocyanate afforded
32 (130 mg, 41%) as a white foam. IR (KBr) [m
/cmꢀ1]: 3508, 3466,
2971, 2936, 1741, 1688, 1579, 1545, 1512, 1489, 1461, 1378,
1246, 1165, 1111, 1053, 1010, 951, 834, 806, 762, 699. 1H NMR
(500 MHz, CDCl3) [d/ppm] 2-methoxybiphenyl: 7.65 (2 ꢁ CH), 7.38