8194
A.M.S. Soares et al. / Tetrahedron 66 (2010) 8189e8195
n
¼3343, 2924, 2853, 1754, 1743, 1687, 1527, 1455, 1359, 1310, 1263,
1506,1457,1426,1409,1382,1366,1278,1254,1245,1231,1202,1179,
1165,1140, 1080,1046, 1025, 971, 911, 888, 869, 778, 751, 697. UV/vis
1241, 1180, 1168, 1121, 1076, 937, 833, 749, 698, 666. UV/vis (ethanol,
nm): lmax (log
3
)¼270 (3.60). HRMS (ESI): calcd for C19H19N2O5
(ethanol, nm): lmax (log
3
)¼301 (4.04). HRMS (ESI): calcd for
[Mþþ1]: 355.12885; found: 355.12853.
C23H20N2O5 [Mþþ1]: 405.1444; found: 405.1445.
4.3.2. N-(Benzyloxycarbonyl)-
ester 8b. Compound 1 (0.193 g, 0.910 mmol), DMF (3 mL), potas-
sium fluoride (0.159 g, 2.73 mmol), and Z- -Ala-OH 7b (0.216 g,
0.910 mmol) were used and the reaction time was 24 h. Ethyl
acetate/n-hexane 1:1 was used as column chromatography eluent
to give compound 8b as a yellow oil (0.159 g, 49%). 1H NMR (CDCl3,
b
-alanine (benzo[d]oxazole) methyl
4.3.5. N-(Benzyloxycarbonyl)-L-alanine (8-methyl-6-oxo-6H-benzo-
pyrano[6,7-d]oxazole) methyl ester 10a. Compound 5 (0.100 g,
0.340 mmol), DMF (3 mL), potassium fluoride (0.059 g, 9.25 mmol),
and Z-Ala-OH 7a (0.076 g, 0.340 mmol) were used and the reaction
time was 5 h. Ethyl acetate/n-hexane 1:1 was used as column
chromatography eluent to give compound 10a as a white solid
(0.078 g, 53%). Mp¼124.2e125.5 ꢂC. 1H NMR (CDCl3, 400 MHZ):
b
300 MHZ):
d
¼2.72 (t, J 6.0 Hz, 2H,
a-CH2 b-Ala), 3.57e3.63 (m, 2H,
b
-CH2 -Ala), 5.12 (s, 2H, CH2 Z), 5.40 (s, 2H, CH2), 6.01 (br s, 1H,
b
d
¼1.53 (d, J 7.2 Hz, 3H, CH3 Ala), 2.51 (d, J 0.4 Hz, 3H, CH3) 4.56 (m,
NH), 7.28e7.36 (m, 7H, H-5, H-6, and 5ꢁAreH Z), 7.50 (dd, J 7.2 Hz,
1H, -CH Ala), 5.10e5.20 (m, 2H, CH2 Z), 5.34 (d, J 6.8 Hz, 1H, -NH
a
a
1H, H-7), 7.62 (d, J 7.8 Hz, 1H, H-4). 13C NMR (CDCl3, 75.4 MHZ):
Ala), 5.39e5.50 (m, 2H, CH2), 6.33 (d, J 1.6 Hz, 1H, H-7), 7.28e7.40
d
¼34.63 (
a-CH2 b-Ala), 36.70 (b-CH2 b-Ala), 58.13 (CH2), 66.77
(m, 5H, 5ꢁAreH Z), 7.51 (s, 1H, H-4), 7.96 (s, 1H, H-9). 13C NMR
(CH2 Z), 110.73 (C-7), 120.33 (C-4), 124.69 (C-6), 125.56 (C-5),
128.09 (AreC), 128.18 (2ꢁAreC), 128.48 (2ꢁAreC), 136.42 (AreC),
140.41 (C-3a) 150.78 (C-7a), 156.44 (C]O urethane), 160.51 (C-2),
(CDCl3, 100.6 MHZ):
d
¼18.48 (CH3 Ala), 19.19 (CH3), 49.59 (
a-CH
Ala), 58.56 (CH2), 67.07 (CH2 Z), 99.67 (C-4), 114.32 (C-7), 115.74 (C-
9), 117.96 (C-8a),128.07 (AreC), 128.21 (2ꢁAreC), 128.52 (2ꢁAreC),
136.07 (AreC), 137.62 (C-9a), 152.06 (C-4a), 152.30 (C-8), 152.33 (C-
3a),155.56 (C]O urethane), 160.33 (C-6), 161.64 (C-2),172.23 (C]O
171.36 (C]O ester). IR (cmꢀ1):
n
¼3332, 3064, 3034, 2950, 2894,
1954, 1747, 1721, 1617, 1577, 1526, 1455, 1401, 1367, 1241, 1162, 1106,
1077, 1003, 936, 884, 832, 747, 698, 666. UV/vis (ethanol, nm): lmax
ester). IR (KBr 1%, cmꢀ1):
n
¼3307, 3065, 2986, 2957, 1723, 1716,
(log
3
)¼270 (3.64). HRMS (ESI): calcd for C19H18N2O5 [Mþþ1]:
1694, 1634, 1577, 1538, 1440, 1391, 1342, 1291, 1259, 1206, 1170,
1133, 1095, 1071, 1055, 1028, 977, 956, 932, 887, 842, 813, 778, 666.
355.12885; found: 355.12999.
UV/vis (ethanol, nm): lmax (log
3
)¼323 (4.01). HRMS (ESI): calcd for
4.3.3. N-(Benzyloxycarbonyl)-
L
-alanine
(naphtho[2,3-d]oxazole)
C23H21N2O7 [Mþþ1]: 437.13433; found: 437.13406.
methyl ester 9a. Compound 2 (0.080 g, 0.305 mmol), DMF (3 mL),
potassium fluoride (0.053 g, 0.916 mmol), and Z-Ala-OH 7a
(0.068 g, 0.305 mmol) were used and the reaction time was 5 h.
Ethyl acetate/n-hexane 1:1 was used as column chromatography
eluent, to give compound 9a as a white solid (0.123 g, 99%).
4.3.6. N-(Benzyloxycarbonyl)-b-alanine (8-methyl-6-oxo-6H-benzo-
pyrano[6,7-d]oxazole) methyl ester 10b. Compound 5 (0.030 g,
0.102 mmol), DMF (2 mL), potassium fluoride (0.018 g, 3.07 mmol),
and Z-b-Ala-OH 7b (0.024 g, 0.102 mmol) were used and the re-
Mp¼138.7e139.9 ꢂC. 1H NMR (CDCl3, 300 MHZ):
d
¼1.55 (d, J
action time was 5 h. Mixtures of increasing polarity of ethyl acetate/
n-hexane were used as the dry flash chromatography eluent to give
compound 10b as a yellow solid (0.042 g, 95%). Mp¼114.6e115.4 ꢂC.
7.2 Hz, 3H, CH3 Ala), 4.60 (t, J 4.0 Hz, 1H,
2H, CH2 Z), 5.37e5.56 (m, 3H, CH2, and
a
-CH Ala), 5.08e5.20 (m,
a
-NH Ala), 7.27e7.39 (m,
5H, 5ꢁAreH Z), 7.47e7.56 (m, 2H, H-6, and H-7), 7.92 (s, 1H, H-9)
1H NMR (CDCl3, 400 MHZ):
d
¼2.40 (s, 3H, CH3), 2.74 (t, J 6.0 Hz, 2H,
7.95 (d, J 8.2 Hz, 1H, H-8), 8.0 (d, J 8.4 Hz, 1H, H-5), 8.19 (s, 1H, H-4).
a-CH2 b-Ala), 3.58e3.63 (m, 2H, b-CH2 b-Ala), 5.13 (s, 2H, CH2 Z),
13C NMR (CDCl3, 75.4 MHZ):
d
¼18.52 (CH3 Ala), 49.63 (
a
-CH Ala),
5.41 (s, 2H, CH2), 5.82 (br s, 1H, NH), 6.31 (d, J 0.8 Hz, 1H, H-7),
7.25e7.40 (m, 5H, 5ꢁAreH Z), 7.50 (s, 1H, H-4), 7.89 (s, 1H, H-9).
58.93 (CH2), 67.03 (CH2 Z), 106.78 (C-9), 118.05 (C-4), 124.91 (C-7),
125.84 (C-6), 127.92 (C-8), 128.02 (AreC), 128.07 (AreC), 128.17
(AreC), 128.50 (AreC), 128.53 (AreC), 128.58 (C-5), 131.31 (C-8a),
131.79 (C-4a), 136.12 (AreC), 140.39 (C-3a), 149.49 (C-9a), 155.59
(C]O urethane), 162.20 (C-2), 172.28 (C]O ester). IR (KBr 1%,
13C NMR (CDCl3, 100.6 MHZ):
36.72 (b-CH2 b-Ala), 57.91 (CH2), 66.72 (CH2 Z), 99.66 (C-4), 114.27
d
¼19.08 (CH3), 34.55 (
a-CH2 b-Ala),
(C-7), 115.60 (C-9), 117.94 (C-8a), 127.91 (AreC), 128.12 (AreC),
128.30 (AreC), 128.55 (2ꢁAreC), 136.42 (AreC), 137.42 (C-9a),
151.98 (C-4a), 152.26 (C-8), 152.39 (C-3a), 156.40 (C]O urethane),
160.37 (C-6), 162.29 (C-2), 171.30 (C]O ester). IR (KBr 1%, cmꢀ1):
cmꢀ1):
n
¼3339, 2943, 1764, 1685, 1619, 1578, 1528, 1463, 1409,
1386, 1365, 1308, 1262, 1243, 1209, 1167, 1149, 1123, 1078, 1046,
1029, 961, 931, 914, 882, 870, 864, 846, 785, 699. UV/vis (ethanol,
n
¼3366, 3060, 3047, 2958, 2927, 2852, 1742, 1716, 1691, 1631, 1600,
nm): lmax (log
3
)¼302 (3.95). HRMS (ESI): calcd for C23H21N2O5
1576, 1535,1498, 1455, 1441, 1418, 1394, 1347, 1324,1311, 1289, 1261,
1211,1166, 1133,1081,1069, 1030, 1013, 975, 938, 920, 894, 884, 816,
[Mþþ1]: 405.14450; found: 405.14408.
784, 739, 666. UV/vis (ethanol, nm): lmax (log
3
)¼323 (4.01). HRMS
4.3.4. N-(Benzyloxycarbonyl)-
methyl ester 9b. Compound 2 (0.031 g, 0.120 mmol), DMF (2 mL),
potassium fluoride (0.021 g, 0.361 mmol), and Z- -Ala-OH 7b
b-alanine
(naphtho[2,3-d]oxazole)
(ESI): calcd for C23H21N2O7 [Mþþ1]: 437.1353; found: 437.1343.
b
4.3.7. N-(Benzyloxycarbonyl)-L-alanine (8-methyl-2-methyl-6-oxo-
(0.028 g, 0.120 mmol) were used and the reaction time was 5 h.
Mixtures of increasing polarity of ethyl acetate/n-hexane were used
as the dry flash chromatography eluent, to give compound 9b as
a yellow solid (0.044 g, 90%). Mp¼105.6e106.9 ꢂC. 1H NMR (CDCl3,
6H-benzopyrano[6,7-d]oxazole) methyl ester 11a. Compound
6
(0.077 g, 0.308 mmol), DMF (3 mL), potassium fluoride (0.054 g,
0.925 mmol), and Z-Ala-OH 7a (0.069 g, 0.308 mmol) were used
and the reaction time was 24 h. Ethyl acetate/n-hexane 1:1 was
used as column chromatography eluent to give compound 11a as
a light pink solid (0.116 g, 86%). Mp¼159.4e160.5 ꢂC. 1H NMR
300 MHZ):
d¼2.76 (t, J 5.7 Hz, 2H,
a-CH2 b-Ala), 3.55e3.75 (m, 2H, b-
CH2 b-Ala), 5.15 (s, 2H, CH2 Z), 5.45 (s, 2H, CH2), 6.15 (br s, 1H, NH),
7.30e7.42 (m, 5H, 5ꢁAreH Z), 7.43e7.60 (m, 2H, H-6, and H-7),
7.80e8.00 (m, 3H, H-9, H-8, and H-5), 8.07 (s, 1H, H-4). 13C NMR
(CDCl3, 400 MHZ):
4.53 (t, J 7.2 Hz, 1H,
(m, 3H, a-NH Ala, and CH2), 6.50 (s, 1H, H-7), 7.30e7.40 (m, 5H,
d
¼1.50 (d, J 7.2 Hz, 3H, CH3 Ala), 2.68 (s, 3H, CH3),
a
-CH Ala), 5.04e5.19 (m, 2H, CH2 Z), 5.33e5.50
(CDCl3, 75.4 MHZ):
d
¼34.74 (
a
-CH2 b-Ala), 36.80 (
b
-CH2 b-Ala), 58.18
(CH2), 66.78 (CH2 Z), 106.73 (C-9), 117.03 (C-4), 124.86 (C-7), 125.80
(C-6), 127.60 (AreC), 127.90 (AreC), 128.06 (AreC), 128.11 (C-8),
128.24 (AreC), 128.53 (AreC), 128.61 (C-5), 131.28 (C-8a), 131.68 (C-
4a), 136.47 (AreC), 140.06 (C-3a), 149.48 (C-9a), 156.53 (C]O ure-
5ꢁAreH Z), 7.49 (s,1H, H-4), 7.78 (s,1H, H-9). 13C NMR (CDCl3,100.6
MHZ):
d
¼14.56 (CH3), 18.26 (CH3 Ala), 49.72 (
a-CH Ala), 62.20
(CH2), 67.13 (CH2 Z), 99.60 (C-4), 112.44 (C-7), 113.42 (C-9), 114.15
(C-8a), 127.99 (AreC), 128.13 (AreC), 128.20 (AreC), 128.46 (AreC),
128.50 (AreC), 136.04 (AreC), 138.66 (C-9a),148.65 (C-8), 151.57 (C-
4a), 152.68 (C-3a), 155.68 (C]O urethane), 160.10 (C-6), 166.03 (C-
thane), 162.94 (C-2), 171.34 (C]O ester). IR (KBr 1%, cmꢀ1):
n
¼3305,
3066, 2958, 2921, 2850, 1750, 1724, 1715, 1638, 1620, 1577, 1546,