Enzymatic Synthesis of Phenoxazine Chromophores
FULL PAPER
Compound 3a: White solid. Yield: 80%; m.p. 133.68C; 1H NMR
Compound 3g: White solid. Yield=70%; m.p. 1408C; 1H NMR
(300 MHz DMSO): d=7.97 (d, J
H
(300 MHz CDCl3): d=7.90 (d, J
ACHTUNGTRENNUNG
U
T
A
1H; SO2NH), 3.76 (t, J (H,H)=5.7 Hz, 2H; H12), 3.10 (t, J (H,H)=
5.7 Hz, 2H; H14), 1.75 (m, 2H; H13), 1.53 ppm (s, 9H; H11); 13C NMR
(75 MHz CDCl3): d=176.2 (C2), 151.7 (C8), 137.7 (C4), 130.5 (C9), 124.7
(C6), 124.2 (C5), 115.3 (C7), 60.4 (14), 41.1 (C12), 32.3 (C13), 30.1 (C10),
28.4 ppm (C11); IR (KBr): n˜ =694–101 (SO2NH, 1,2,3-Ar), 1122–1253,
1334 (SO2NH, alcane), 1423–1550 (benzoxazole), 2977 (alcane), 3290–
3460 cmÀ1 (NH, OH); MS (ESI): m/z (%): 313.1 (100) [M+H]+, 335.1
(60) [M+Na]+; HRMS (ESI): m/z: calcd for C14H21N2O4S: 313.1222;
found: 313.1218.
Compound 3b: White solid; Yield=80%; m.p. 1308C; 1H NMR
(300 MHz DMSO): d=7.95 (d,
(H,H)=7.8 Hz, 1H; H7), 7.52 (d, J
(dd, J(H,H)=7.6, 7.7 Hz, 1H; H6), 3.60 (brs, 1H; H12), 1.60 (m, 4H;
JACHTUNGTRENNUNG
General procedure for the synthesis of compounds 4a–g: Compound 3a–
g (1 mmol) was added to a solution of 6 n aqueous HCl (100 mL). The
mixture was heated at 1008C overnight. Then the solution was cooled
down, filtered and evaporated. The residue was purified by column chro-
matography on flash silica gel (Et2O/EtOAc, 7:3) to give the title com-
pound. The purity of the compound was checked by HPLC.
J
N
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
H13, H17), 1.50 (s, 9H; H11), 1.15 ppm (m, 6H; H14–16); 13C NMR
(75 MHz DMSO): d=174.8 (C2), 151.5 (C8), 137.5 (C4), 133.7 (C9),
125.0 (C6), 123.3 (C5), 115.2 (C7), 52.5 (C12), 34.4 (C10), 34.2 (C13,
C17), 28.5 (C11), 25.2 ppm (C14–16); IR (KBr): n˜ =675–929 (SO2NH,
1,2,3-Ar), 1145, 1203–1292 (SO2NH), 1562–1604 (benzoxazole), 2920
(alcane), 3305 cmÀ1 (NH); MS (ESI): m/z (%): 337.01 (70) [M+H]+,
255.14 (100), 256.09 (35), 270.02 (15); HRMS (ESI): m/z: calcd for
C17H24N2O3NaS: 359.1412; found: 359.1405.
Compound 4a: Yellow powder. Yield=30%; m.p. 192.18C; 1H NMR
(300 MHz CD3OD): d=7.20 (dd, J
(dd, J(H,H)=7.8, 1.5 Hz, 1H; H4), 6.56 ppm (dd, J
1H; H5); 1H NMR 300 MHz (DMSO): d=7.20 (brs, 1H), 7.10 (dd,
(H,H)=8.1 Hz, 1.3 Hz, 1H; H6), 6.82 (dd, J(H,H)=7.7, 1.2 Hz, 1H;
H4), 6.50 (dd, J (H,H)=
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
Compound 3c: White gummy solid. Yield=80%; 1H NMR (300 MHz
J
N
ACHTUNGTRENNUNG
ACHUTNGREN(NUG H,H)=8.1, 7.6 Hz, 1H; H5), 5.31 ppm (d, JACHTUNGTRENNUNG
DMSO): d=7.99 (d, J
ACHTUNGTRENNUNG
4.9 Hz, 2H; SO2NH2); 13C NMR (75 MHz DMSO): d=145.2 (C3), 135.1
(C1), 125.1 (C2), 118.6 (C5), 116.7 (C6), 115.1 ppm (C4); IR (KBr): n˜ :
667–720 (SO2NH), 1130–1180, 1298–1323 (SO2NH, 1,2,3-Ar), 1500, 1620
7.75 (d, J(H,H)=7.8 Hz, 1H; H7), 7.52 (dd, JACTHUNGTRENNUNG
G
H6), 3.12 (m, 2H; H12), 2.99 (m, 2H; H14), 2.66 (s, 6H; H15), 1.83 (m,
2H; H13), 1.51 ppm (s, 9H; H11); 13C NMR (75 MHz DMSO): d=175.0
(C2), 151.5 (C8), 137.7 (C4), 131.9 (C9), 125.0 (C6), 123.7 (C5), 115.5
(C7), 54.7 (C12), 42.5 (C15), 39.1 (C14), 34.5 (C10), 28.6 (C11), 25.1 ppm
(C13); IR (KBr): n˜ =670–760 (SO2NH), 1099–1180–1253 (SO2NH,
NMe2), 1542–1604 (benzoxazole), 2920, 3440 cmÀ1; MS (ESI): m/z (%):
340.36 (70) [M+H]+, 295.24 (10), 266.96 (10); HRMS (ESI): m/z: calcd
for C16H26N3O3S: 340.1695; found: 340.1695.
(ArNH2), 3230–3430 cmÀ1 (NH2); UV/Vis (H2O/CH3SO3H): lmax
=
310 nm; MS (ESI): m/z (%): 187.1 [M<M->H]+, 188.08 [M]+ (100),
79.8 (45); HRMS (ESI): m/z: calcd for C6H9N2O3S: 189.0334; found:
189.0331.
Compound 4b: Rose-coloured foam. Yield=95%; m.p. 165.68C;
1H NMR 300 MHz (CD3OD): d=7.50 (dd, J
ACHTUNGTRENNUNG
Compound 3d: Brown solid. Yield=80%; m.p. 1898C; 1H NMR
H6), 7.20 (d, J
N
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
(300 MHz DMSO): d=10.40 (s, 1H; SO2NH), 7.95 (dd, J
0.9 Hz, 1H; H5), 7.80 (dd, J(H,H)=7.9, 0.6 Hz, 1H; H7), 7.50 (dd, J-
ACHTUNGTRENNUNG(H,H)=8.1, 7.9 Hz, 1H; H6), 7.14 (m, 4H; H13,14,16,17), 6.93 (m, 1H;
ACHTUNGTRENUN(NG H,H)=8.1,
(m, 4H; H8, H12), 1.51 ppm (m, 6H; H9–11); 13C NMR 125 MHz
(CD3OD): d=146.6 (C3), 135.6 (C1), 122.7 (C2), 119.8 (C5), 117 (C6),
115.8 (C4), 52.6 (C7), 33.8 (C8, C12), 25.4 (C9, C11), 25.1 ppm (C10); IR
(KBr): n˜ =650–780 (SO2NH), 1080–1240, 1296–1326 (SO2NH), 1440–1480
(alcane), 1616 (ArNH2), 2800–3040 (alcane), 3200–3400 cmÀ1 (NH); UV/
Vis (H2O/CH3SO3H): lmax =319 nm; MS (ESI): m/z (%): 270.90 [M+H]+
(100), 204.11 (15), 189.01 (20); HRMS (ESI): m/z: calcd for
C12H18N2O3NaS: 293.0936; found: 293.0931.
AHCTUNGTRENNUNG
H15), 1.44 ppm (s, 9H; H11); 13C NMR (75 MHz DMSO): d=175.2
(C2), 151.3 (C8), 137.9 (C4), 130.3 (C9), 129.2 (C13,17), 125.0 (C6), 124.1
(C5), 120.0 (C14–16), 116.0 (C7), 34.5 (C10), 28.5 ppm (C11); IR (KBr):
n˜ =650–756 (Ar, SO2NH), 1203–1485 (SO2NH, Ar), 1594 (benzoxazole),
3450 cmÀ1 (NH); MS (ESI): m/z (%): 331.09 (100) [M+H]+, 393.14 (10),
496.18 (25); HRMS (ESI): m/z: calcd for C17H18N2O3NaS: 353.0936;
found: 353.0943.
Compound 4c: Rose-coloured foam. Yield=95%; m.p. 1058C; 1H NMR
(300 MHz CD3OD): d=7.33 (t, J
(H,H)=7.9, 1.4 Hz,1H; H6), 7.21 (dd, J
3.20 (td, J(H,H)=1.6, 3.3 Hz, 2H; H7), 3.06 (t, JCAHTUNGTRENNNUG
1
ACHTUNGTRENNUNG
Compound 3e: White solid. Yield=75%; m.p. 908C; H NMR (300 MHz
N
ACHTUNGTRENNUNG
CDCl3): d=7.84 (d, J
1H; H7), 7.41 (dd, J(H,H)=7.7, 8.2 Hz, 1H; H6), 3.01 (dd, J
5.0 Hz, 6.5 Hz, 2H; H12), 2.80 (dd, J(H,H)=5 Hz, 6.4 Hz, 2H; H13),
ACHTUNGTRENNUNG(H,H)=7.7 Hz,1H; H5), 7.70 (d, JCAHTUNGTRENNUNG
N
A
ACHTUNGTRENNUNG
H9), 2.90 (s, 6H; H10), 1.91 ppm (m, 2H; H8);13C NMR (125 MHz
DMSO): d=146.7 (C3), 133.9 (C1), 121.1 (C2), 119.2 (C5), 117.3 (C6),
116.2 (C4), 54.9 (C7), 42.7 (C9–10), 23.9 ppm (C8); IR (KBr): n˜ =650–
790 (SO2NH), 1072–1326 (SO2NH, NMe2), 1420–1480 (alcane), 1620
(ArNH2), 2711–3300, 3400 cmÀ1 (NH, hydrogen bonding); UV/Vis (H2O/
CH3SO3H): lmax =317 nm; MS (ESI): m/z (%): 274.13 [M+H]+ (100),
275.14 (20), 340.16 (7); HRMS (ESI): m/z: calcd for C11H20N3O3S:
274.1225; found: 274.1229.
AHCTUNGTRENNUNG
1.50 ppm (s, 9H; H11); 13C NMR (75 MHz DMSO): d=176.1 (C2), 151.8
(C8), 137.8 (C4), 130.7 (C9), 124.6 (C6), 124.0 (C5), 115.2 (C7), 46.4
(C12), 41.7 (C13), 34.9 (C10), 28.8 ppm (C11); IR (KBr): n˜ =736–756
(SO2NH), 933, 1087–1203 (SO2NH), 1427 (alcane), 1558 (benzoxazole),
3280 cmÀ1 (NH); MS (ESI): m/z (%): 298.1 (100) [M+H]+, 320 (7),
281.24 (5), 594.64 (5); HRMS (ESI): m/z: calcd for C13H19N3O3NaS:
320.1045; found: 320.1053.
Compound 4d: Red gummy solid. Yield=30%; 1H NMR (500 MHz
DMSO): d=7.20 (m, 2H; H8, H12), 7.04 (m, 3H; H9, H11, H6), 6.96 (m,
1H; H10), 6.80 (dd, JACTHUNRGTENN(UG H,H)=7.6, 1.1 Hz, 1H; H4), 6.43 (dd, JACHTUNGTRENNUNG(H,H)=
1
Compound 3 f: White solid. Yield=70%; m.p. 928C; H NMR (300 MHz
CDCl3): d=7.84 (d, J
1H; H7), 7.40 (dd, J(H,H)=7.8, 8.4 Hz, 1H; H6), 5.90 (m, 1H; SO2NH),
4.10 (dd, J(H,H)=7.1, 14.3 Hz, 2H; H14), 4.01 (d, J(H,H)=5.4 Hz, 2H;
H12), 1.51 (s, 9H; H11), 1.20 ppm (t, (H,H)=7.1 Hz, 3H; H15);
ACHTUNGTRENNUNG(H,H)=7.8 Hz,1H; H5), 7.71 (d, JACHTUNGTNER(NUGN H,H)=8.4 Hz,
ACHTUNGTRENNUNG
7.6, 7.9 Hz, H5), 5.41 ppm (brs, 2H; NH2); 13C NMR (125 MHz DMSO):
d=145.7 (C3), 138.7 (C1), 136.7 (C2), 129.8 (C8, C12), 124.1 (C7), 120.5
(C5), 119.8 (C9, C11), 119.7 (C10), 117.8 (C6), 115.3 ppm (C4); IR
(KBr): n˜ =670–729 (SO2NH), 921 (Ar), 1080 (Ar), 1137–1184 (Ar), 1276–
1315 (SO2NH), 1496, 1620 (ArNH2), 3200, 3300 cmÀ1 (NH); UV/Vis
(H2O/CH3SO3H): lmax =320 nm; MS (ESI): m/z (%): 265.02 [M+H]+
(100), 266.06 (10), 197.22 (10); HRMS (ESI): m/z: calcd for
C12H13N2O3S: 265.0647; found: 265.0640.
A
ACHTUNGTRENNUNG
JACHTUNGTRENNUNG
13C NMR (75 MHz CDCl3): d=175.7 (C2), 168.6 (C13), 151.4 (C8), 137.8
(C4), 130.1 (C9), 124.1 (C6), 123.4 (C5), 115.0 (C7), 61.6 (C14), 44.8
(C12), 34.5 (C10), 28.4 (C11), 14.0 ppm (C15); IR (KBr): n˜ =694–101
(SO2NH, 1,2,3-Ar), 1122–1253, 1334 (SO2NH, alcane), 1423–1550 (ben-
zoxazole), 1740 (CO), 2977 (hydrogen bonding), 3271 cmÀ1 (NH); MS
(ESI): m/z (%): 298.1 (100) [M+H]+, 341.32 (60), 363.11 (100) [M+Na]+,
702.61 (100); HRMS (ESI): m/z: calcd for C15H20N2O5NaS: 363.0991;
found: 363.0995.
Compound 4e: Rose-coloured foam. Yield=95%; m.p. 176.18C;
1H NMR (300 MHz CD3OD): d=7.42 (dd, J
ACTHNUTRGNEUNG(H,H)=7.8, 1.2 Hz, 1H;
Chem. Eur. J. 2009, 15, 8283 – 8295
ꢃ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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