R. Schobert et al. / Tetrahedron 62 (2006) 7799–7808
7807
3.1.2.7. Pentabenzylated conjugate 24a. A solution of
methyl 6-aminopenicillanate 4 (110 mg, 0.48 mmol), 3
(174 mg, 0.58 mmol), 23a (705 mg, 0.48 mmol) and a cata-
lytic amount of benzoic acid in THF (20 mL) was stirred at
room temperature over night. The solvent was removed un-
der reduced pressure and the residue was purified by column
chromatography (silica gel 60, cyclohexane/ethyl acetate
1:2 v/v, Rf 0.33) to yield 24a (415 mg, 62%) as a colourless
foamy solid; nmax/cmꢁ1 2926, 1785, 1723, 1653, 1581,
1474; d0H (300 MHz; CDCl3) 1.46 (3H, s, CH3), 1.61 (3H,
s, CH3 ), 2.45–2.55 (4H, m, O]CCH2, BnONCCH2),
OCOCCH2, NH(CO)CH2), 2.65 (2H, t, 3J¼6.1 Hz,
ON(CO)CH2), 2.80–3.00 (6H, m, NCH2), 3.25 (4H, t,
3
3J¼5.9 Hz, OCOCH2), 3.67 (2H, t, J¼5.8 Hz, ONCH2),
3
3.70 (3H, s, OCH3), 4.12 (4H, t, J¼6.0 Hz, NCCH2OR),
4.35–4.45 (5H, m, OCOCH2, CHCO2Me), 5.50 (1H, d,
3J¼4.6 Hz, SCH), 5.70–5.80 (1H, m, SCHCH), 6.73 (2H,
3
3
4
t, J¼8.1 Hz, Har), 6.93 (2H, dd, J¼8.1, J¼1.7 Hz, Har),
7.20 (2H, dd, 3J¼8.1, 4J¼1.7 Hz, Har); dC (75 MHz;
MeOD-d3) 23.7, 26.3, 27.1, 27.4, 30.8, 31.3, 31.8, 33.9,
48.0, 52.5, 52.7, 54.3, 58.2, 62.8, 63.4, 64.5, 70.4, 76.1,
117.8, 118.6, 119.2, 125.9, 147.8, 151.2, 168.1, 169.2,
171.5, 172.0, 174.6, 175.6. Anal. Calcd for C43H56N4O18S:
C, 54.4; H, 6.0; N, 5.9. Found: C, 54.0; H, 5.8; N, 6.1%.
3
2.70–2.90 (6H, m, NCH2), 3.71 (2H, t, J¼5.9 Hz, BnO–
N–CH2), 3.77 (3H, s, OCH3), 4.12 (4H, t, 3J¼6.2 Hz,
NCCH2OR), 4.39 (1H, s, CHCO2Me), 4.76 (2H, s, N–O–
3
4
CH2Ph), 4.83 (4H, dd, J¼4.8, J¼1.8 Hz, OCH2C]C),
5.06 (4H, s, C–O–CH2Ph), 5.12 (4H, s, C–O–CH2Ph), 5.52
(1H, d, 3J¼4.3 Hz, SCH), 5.72 (1H, dd, 3J¼4.3,
3.1.2.10. Conjugate 2b. Analogously to 13a (Section
3.1.1.13), 2b (118 mg, 64%) was obtained after a 24 h reac-
tion period as a faintly yellow solid of mp 160–163 ꢀC from
24b (280 mg, 0.20 mmol), [a]2D0 46 (c 1.0, EtOH); nmax/cmꢁ1
3356, 2928, 1782, 1741, 1680, 1642, 1584; dH (300 MHz;
3
3J¼7.1 Hz, SCHCH), 5.85 (1H, d, Jtrans¼16.0 Hz,
3
NCOCH]C), 6.06 (2H, dt, Jtrans¼15.9, 4J¼1.8 Hz,
3
0
OCOCH]C), 6.31 (1H, d, J¼7.1 Hz, NH), 6.80 (1H, dt,
MeOD-d3) 1.40 (3H, s, CH3), 1.59 (3H, s, CH3 ), 1.60–
3Jtrans¼16.0, 3J¼4.6 Hz, NCOC]CH), 6.93 (2H, dt,
3Jtrans¼15.9, 3J¼4.8 Hz, OCOC]CH), 7.05–7.20 (6H, m),
7.30–7.55 (25H, m); dC (75 MHz; CDCl3) 27.0, 29.6, 30.9,
31.4, 50.3, 52.4, 52.7, 58.6, 62.7, 63.0, 64.8, 68.1, 70.5,
71.0, 71.3, 75.6, 76.4, 118.3, 122.7, 123.8, 125.0, 126.2,
126.8, 127.1, 127.4, 127.7, 128.0, 128.1, 128.5, 136.1,
136.4, 137.0, 141.5, 149.9, 152.8, 163.5, 164.0, 165.6,
168.1, 170.7, 173.8. Anal. Calcd for C78H82N4O18S: C,
67.1; H, 5.9; N, 4.0. Found: C, 66.8; H, 6.1; N, 4.1%.
1.75 (4H, m, ONC(CH2)2), 2.10–2.25 (4H, m, NHCH2CH2),
2.24 (2H, t, 3J¼6.1 Hz, NCOCH2), 2.69 (2H, t, 3J¼6.0 Hz,
ONCOCH2), 2.80–3.00 (6H, m, NCH2), 3.23 (4H, t,
3J¼5.8 Hz, OCOCH2), 3.68 (3H, s, OCH3), 3.70–3.90
(6H, m, NHCH2, HONCH2), 4.14 (4H, t, 3J¼6.1 Hz,
NCCH2OR), 4.33 (1H, s, CHCO2Me), 5.48 (1H, d,
3J¼4.4 Hz, SCH), 5.75–5.85 (1H, m, Hz, SCHCH), 6.70
3
3
4
(2H, t, J¼8.0 Hz, Har), 6.92 (2H, dd, J¼8.0, J¼1.5 Hz,
Har), 7.21 (2H, dd, J¼8.0, J¼1.5 Hz, Har), 8.02 (2H, t,
3J¼7.3 Hz, NH); dC (75 MHz; MeOD-d3) 23.5, 25.8, 27.0,
27.2, 31.5, 31.9, 32.4, 33.8, 40.0, 48.3, 52.4, 52.5, 54.0,
58.1, 63.3, 63.6, 71.3, 76.1, 117.3, 118.8, 119.6, 119.9,
148.0, 150.5, 165.7, 168.8, 170.1, 170.7, 172.0, 174.9.
Anal. Calcd for C43H58N6O16S: C, 54.5; H, 6.2; N, 8.9.
Found: C, 54.7; H, 6.1; N, 8.7%.
3
4
3.1.2.8. Pentabenzylated conjugate 24b. Analogously
to 24a (Section 3.1.2.7), 24b (298 mg, 51%) was obtained
as a pale yellow foamy solid from 4 (97 mg, 0.42 mmol), 3
(154 mg, 0.51 mmol) and 23b (610 mg, 0.42 mmol); Rf
0.30 (cyclohexane/ethyl acetate 1:4 v/v); nmax/cmꢁ1 2928,
1783, 1719, 1661, 1576, 1524; dH (0300 MHz; CDCl3) 1.44
(3H, s, CH3), 1.62 (3H, s, CH3 ), 2.40–2.55 (4H, m,
O]CCH2, BnONCCH2), 2.73 (4H, t, 3J¼6.2 Hz,
NCH2COR), 2.86 (2H, t, 3J¼6.4 Hz, NCH2CCO), 3.67
(2H, t, 3J¼5.8 Hz, BnO–N–CH2), 3.71 (3H, s, OCH3),
3.90–4.00 (4H, m, NHCH2), 4.11 (4H, t, 3J¼6.2 Hz,
NCCH2OR), 4.35 (1H, s, CHCO2Me), 4.74 (2H, s, N–O–
CH2Ph), 5.06 (4H, s, C–O–CH2Ph), 5.13 (4H, s, C–O–
3.1.3. Chelators 2520 and 2621 lacking siderophore
activity.
3.1.3.1. Biscatechol-salicylate 25a. Colourless solid of
mp 107–108 ꢀC; nmax/cmꢁ1 3362, 2930, 1734, 1692, 1588;
dH (300 MHz; MeOD-d3) 1.95–2.10 (4H, m, OCOCCH2),
3
2.42 (4H, t, J¼7.1 Hz, OCOCH2C), 2.75–2.95 (6H, m,
NCH2), 4.08 (4H, t, 3J¼5.6 Hz, NCCH2OR), 4.25–4.40
(6H, m, NCCH2OR0, OCCCCH2), 6.75–6.85 (2H, m, Har),
6.90–7.05 (4H, m, Har), 7.20–7.35 (4H, m, Har); dC
(75 MHz; MeOD-d3) 25.1, 32.8, 54.4, 54.6, 64.1, 64.7,
65.8, 113.8, 119.2, 120.5, 121.4, 128.8, 129.6, 131.2,
136.9, 146.8, 147.2, 151.6, 162.8, 171.7, 174.6, 175.3.
Anal. Calcd for C35H39NO15: C, 58.9; H, 5.5; N, 2.0. Found:
C, 58.6, H, 5.4, N, 2.1%.
3
CH2Ph), 5.51 (1H, d, J¼4.2 Hz, SCH), 5.70–5.85 (3H, m,
3
SCHCH, OCOCH]C), 5.79 (1H, d, Jtrans¼15.8 Hz,
NCOCH]C), 6.46 (1H, d, 3J¼7.3 Hz, NH), 6.65–6.80
(3H, m, NCOC]CH, OCOC]CH), 7.05–7.15 (4H, m),
7.25–7.50 (25H, m), 7.90–8.00 (2H, m), 8.13 (2H, t,
3J¼7.1 Hz, NH); dC (75 MHz; CDCl3) 27.0, 32.1, 32.3,
34.8, 40.2, 49.7, 52.3, 52.6, 58.1, 58.2, 62.4, 64.6, 68.8,
70.5, 71.3, 76.4, 76.6, 117.3, 121.5, 123.3, 124.3, 126.6,
127.2, 127.5, 128.0, 128.4, 128.6, 128.7, 128.8, 129.0,
136.1, 136.3, 137.5, 144.1, 146.8, 152.6, 161.2, 163.8,
165.1, 165.8, 170.6, 174.0. Anal. Calcd for C78H84N6O16S:
C, 67.2; H, 6.1; N, 6.0. Found: C, 66.9; H, 6.2; N, 5.9%.
3.1.3.2. Biscatechol-salicylate 25b. Colourless solid of
mp 111–113 ꢀC; nmax/cmꢁ1 3363, 2928, 1737, 1642, 1583,
1460; dH (300 MHz; MeOD-d3) 1.85–1.95 (4H, m,
3
OCCCH2), 2.39 (4H, t, J¼7.0 Hz, OCCH2C), 2.80–2.95
(6H, m, NCH2), 3.30–3.40 (4H, m, NHCH2), 4.17 (4H, t,
3J¼5.6 Hz, NCCH2OR), 4.51 (2H, t, 3J¼5.5 Hz,
NCCH2OR0), 6.65–6.85 (4H, m, Har), 7.00–7.30 (6H, m,
Har); dC (75 MHz; MeOD-d3) 25.5, 32.0, 39.6, 54.4, 54.5,
62.8, 63.6, 113.5, 117.1, 118.6, 120.3, 121.4, 121.9, 122.2,
128.0, 136.6, 148.2, 151.4, 161.3, 171.0, 171.7, 174.6.
Anal. Calcd for C35H41N3O13: C, 59.1; H, 5.8; N, 5.9.
Found: C, 58.7; H, 6.0; N, 5.7%.
3.1.2.9. Conjugate 2a. Analogously to 13a (Section
3.1.1.13), 2a (161 mg, 60%) was obtained after a 24 h reac-
tion period as a colourless solid of mp 154–156 ꢀC from 24a
(400 mg, 0.29 mmol), [a]2D0 48 (c 1.0, EtOH); nmax/cmꢁ1
3358, 2930, 1785, 1738, 1681, 1635; dH (300 MHz;
0
MeOD-d3) 1.38 (3H, s, CH3), 1.55 (3H, s, CH3 ),
1.55–1.70 (4H, m, ONCH2(CH2)2), 2.05–2.25 (6H, m,