3916
C. Pichon-Santander et al. / Bioorg. Med. Chem. 14 (2006) 3904–3922
d 166.74 (d, JCH = 70.8, C-4); 150.65 (d, JCH = 78.2, C-
9); 140.11 (d, JCH = 73.2, C-14); 134.15 (d, JCH = 70.9,
C-19); 109.08 (t, JCH = 71.3, C-15); 96.05 (d,
JCH = 80.3, C-10); 95.02 (s, C-20); 89.42 (d,
(s, 3H, CH3 at C-2); 1.31 (s, 3H, CH3 at C-7). UV kmax
(MeOH) 279 (0.26), 357 (0.48), 374 (1), 385 (sh, 0.76),
405 (0.62), 487 (0.12), 540 (0.14), 578 (0.16), 624
(0.12). MS (ESI) m/z 943 [M+H]+.
1
JCH = 73.2, C-5). 7a epimer 2: H NMR (C6D6): d 8.83
(d, JCH = 152.1, 1H, H-15); 7.65 (d, JCH = 140.3, 1H,
H-10); 7.53 (d, JCH = 155.5, 1H, H-20); 6.71 (d,
JCH = 155.6, 1H, H-5); 4.13, 4.12 (2s, 4H, 2 CH2CO2Me
at C-12 and C-18); 4.13, 4.11 (2m, 2H, H-3 and H-8);
3.78 (m, 4H, 2 CH2CH2CO2Me at C-13 and C-17);
3.41, 3.38, 3.35, 3.34, 3.26, 3.23, 3.22, 3.00 (8s, 24H, 8
CO2CH3); 2.98–2.84 (m, 4H, 2 CH2CH2CO2Me at C-
13 and C-17); 2.65–2.50 (m, 4H, 2 CH2CO2Me at C-2
and C-7); 2.48–2.35 (m, 2H, CH2CH2CO2Me at C-8 or
C-3); 2.24, 2.08 (m, 6H, CH2CH2CO2Me at C-3 or C-
8 and CH2CH2CO2Me at C-3 or C-8); 1.59 (s, 3H,
CH3 at C-2); 1.53 (s, 3H, CH3 at C-7). 13C NMR d
161.11 (d, JCH = 70.1, C-4); 154.55 (d, JCH = 79.1, C-
9); 138.73 (d, JCH = 73.1, C-14); 135.25 (d, JCH = 70.6,
C-16); 109.08 (t, JCH = 71.3, C-15); 96.99 (d,
JCH = 77.2, C-10); 93.00 (s, C-20); 90.04 (d,
JCH = 78.6, C-5).
(b) Incubation of CobA and CobI with uro III (1a) gave
3 isolated products: factor 3 methyl ester (8a) (22%), fac-
tor 3 monolactone methyl ester (12a) (8%), and factor 3
dilactone methyl ester (13a) (6%). Factor 3 8a (major
isomer):6 1H NMR (C6D6): d 8.73 (s, 1H, H-15); 7.50
(s, 1H, H-10); 6.51 (s, 1H, H-5); 4.21 (d, J = 19.7, 2H,
CH2CO2Me at C-18); 4.06, 4.04 (2m, 2H, H-3 and H-
8); 4.03 (AB, J = 12.8, 2H, CH2CO2Me at C-12); 3.69
(m, 4H, 2 CH2CH2CO2Me at C-13 and C-17); 3.43,
3.38, 3.37, 3.31, 3.27, 3.26, 3.24, 3.22 (8s, 24H, 8
CO2CH3); 2.92 (2m, 4H, 2 CH2CH2CO2Me at C-13
and C-17); 2.77 (s, 3H, CH3 at C-20); 2.67, 2.50 (AB,
J = 9.1, 2H, CH2CO2Me at C-2 or C-7); 2.65 (s, 2H,
CH2CO2Me at C-2 or C-7); 2.59 (m, 2H,
CH2CH2CO2Me at C-8); 2.29, 2.18, 2.09 (3m, 6H,
CH2CH2CO2Me at C-3 and CH2CH2CO2Me at C-8);
1.66 (s, 3H, CH3 at C-2); 1.40 (s, 3H, CH3 at C-7).
UV kmax (MeOH) 275 (0.24), 361 (sh, 0.59), 381 (1),
410 (sh, 0.52), 500 (0.1), 544 (0.15), 574 (0.17), 633
Factor 2 monolactone 10a (major isomer). 1H NMR
(C6D6): d 8.96 (s, 1H, H-15); 8.06 (s, 1H, H-10); 7.55 (s,
1H, H-20); 6.61 (s, 1H, H-5); 4.16, 4.04 (s + d, J = 2.5,
4H, 2 CH2CO2Me at C-12 and C-18); 4.15 (m, 1H, H-3
or H-8); 3.83 (m, 4H, 2 CH2CH2CO2Me at C-13 and C-
17); 3.43, 3.35, 3.33, 3.32, 3.25, 3.19, 3.16 (7s, 21H, 7
1
(0.07) nm. MS (ESI) m/z 989 [M+H]+. 8a epimer: H
NMR (C6D6): d 9.05 (s, 1H, H-15); 7.76 (s, 1H, H-10);
6.99 (s, 1H, H-5); 4.40, 4.31 (AB, J = 18.2, 2H,
CH2CO2Me at C-12 or C-18); 4.36, 4.05 (2m, 2H, H-3
and H-8); 4.14, 4.03 (AB, J = 12.8, 2H, CH2CO2Me at
C-12 or C-18); 3.87 (m, 4H, 2 CH2CH2CO2Me at C-13
and C-17); 3.43, 3.39, 3.35, 3.27 (2), 3.25, 3.15 (7s,
24H, 8 CO2CH3); 2.98 (m, 4H, 2 CH2CH2CO2Me at
C-13 and C-17); 2.79 (s, 3H, CH3 at C-20); 2.64 (s,
2H, CH2CO2Me at C-2 or C-7); 2.62, 2.44 (AB,
J = 18.2, 2H, CH2CO2Me at C-2 or C-7); 2.29–2.00
(m, 8H, 2 CH2CH2CO2Me at C-3 and C-8); 1.51 (s,
3H, CH3 at C-2); 1.39 (s, 3H, CH3 at C-7).
CO2CH3); 3.01, 2.93 (2t, J = 9.1, 9.1, 4H,
2
CH2CH2CO2Me at C-13 and C-17); 2.80, 2.53 (AB,
J = 18.2, 2H, CH2CO2Me at C-2 or C-7); 2.36 (d,
J = 18.0, 2H, CH2CO2Me at C-7 or C-2); 2.62 (m, 2H,
CH2CH2CO2Me at C-3 or C-8); 2.20–2.00 (m, 6H,
CH2CH2CO2Me at C-3 or C-8 and CH2CH2CO2Me at
C-3 or C-8); 1.75 (s, 3H, CH3 at C-2); 1.21 (s, 3H, CH3
at C-7). UV kmax (MeOH) 280 (0.25), 356 (sh, 0.58), 375
(1), 404 (0.48), 504 (0.1), 538 (0.17), 575 (0.19), 629
1
1
(0.06) nm. MS (ESI) m/z 959 [M+H]+. 10a epimer: H
Factor 3 monolactone 12a. H NMR (C6D6): d 8.85 (s,
NMR (C6D6): d 8.98 (s, 1H, H-15); 7.68 (s, 1H, H-10);
7.53 (s, 1H, H-20); 6.97 (s, 1H, H-5); 4.21 (m, 1H, H-3
or H-8); 4.16, 4.12 (2d, J = 8.2, 8.1, 4H, 2 CH2CO2Me
at C-12 and C-18); 3.84, 3.67 (t + m, J = 7.0, 4H, 2
CH2CH2CO2Me at C-13 and C-17); 3.41, 3.34, 3.33,
3.32, 3.25, 3.23, 3.19 (7s, 21H, 7 CO2CH3); 2.99 (m, 4H,
2 CH2CH2CO2Me at C-13 and C-17); 2.54, 2.30 (AB,
J = 17.5, 2H, CH2CO2Me at C-2 or C-7); 2.52 (s, 2H,
CH2CO2Me at C-2 or C-7); 2.59, 2.37 (2m, 2H,
CH2CH2CO2Me at C-3 or C-8); 2.44 (t, J = 7.0, 2H,
CH2CH2CO2Me at C-3 or C-8); 2.21, 2.09, 2.00 (3m,
4H, 2 CH2CH2CO2Me at C-3 and C-8); 1.44 (s, 3H,
CH3 at C-2); 1.37 (s, 3H, CH3 at C-7).
1H, H-15); 7.88 (s, 1H, H-10); 6.40 (s, 1H, H-5); 4.19
(AB, J = 17.5, 2H, CH2CO2Me at C-18); 4.11 (m, 1H,
H-3 or H-8); 3.94 (AB, J = 7.7, 2H, CH2CO2Me at C-
12); 3.73, 3.64 (2m, 4H, 2 CH2CH2CO2Me at C-13
and C-17); 3.42, 3.40, 3.37, 3.27, 3.24, 3.19, 3.17 (7s,
21H, 7 CO2CH3); 2.99 (d, J = 17.5, CH2CO2Me at C-
7); 2.94, 2.88 (2 AB, J = 6.9, 2 CH2CH2CO2Me at C-
13 and C-17); 2.73 (s, 3H, CH3 at C-20); 2.64 (s, 2H,
CH2CO2Me at C-2); 2.38 (d, J = 18.2, 2H,
CH2CH2CO2Me at C-3 or CH2CH2CO2Me C-8); 2.42,
2.31 (AB, J = 18.0, 2H, CH2CH2CO2Me at C-3 or C-
8); 2.18, 2.00 (2m, 4H, 2 CH2CH2CO2Me at C-3 and
C-8); 1.67 (s, 3H, CH3 at C-2); 1.16 (s, 3H, CH3 at C-
7). UV kmax (MeOH) 274 (0.24), 360 (0.55), 379 (1),
407 (0.52), 500 (0.10), 537 (0.16), 580 (0.17), 631 (0.07)
nm. MS (ESI) m/z 973 [M+H]+.
1
Factor 2 dilactone 11a. H NMR (C6D6): d 9.28 (s, 1H,
H-15); 8.25 (s, 1H, H-10) ; 7.75 (s, 1H, H-20); 7.08 (s,
1H, H-5); 4.24, 4.11 (d + s, J = 2.8, 4H, 2 CH2CO2Me
at C-12 and C-18); 4.06, 3.93, 3.82 (3m, 4H, 2
CH2CH2CO2Me at C-13 and C-17); 3.45, 3.32, 3.26,
3.23, 3.19 (2) (6s, 18H, 6 CO2CH3); 3.04, 2.98 (2t,
J = 8.9, 8.9, 4H, 2 CH2CH2CO2Me at C-13 and C-17);
2.64, 2.37 (AB, J = 17.9, 2H, CH2CO2Me at C-2 or C-
7); 2.53 (s, 2H, CH2CO2Me at C-2 or C-7); 2.59, 2.20–
2.00 (2m, 8H, 2 CH2CH2CO2Me at C-3 and C-8); 1.42
1
Factor 3 dilactone 13a. H NMR (C6D6): d 9.46 (s, 1H,
H-15); 8.38 (s, 1H, H-10); 7.58 (s, 1H, H-5); 4.49 (AB,
J = 18.9, 2H, CH2CO2Me at C-18); 4.16 (s, 2H,
2
CH2CO2Me at C-12); 4.02-3.91 (m, 4H,
CH2CH2CO2Me at C-13 and C-17); 3.43 (2), 3.26,
3.25, 3.20, 3.16 (6s, 18H, 6 CO2CH3); 3.06, 3.02 (2t,
J = 6.8, 4H, 2 CH2CH2CO2Me at C-13 and C-17);