6684
M. O. Anderson et al. / Bioorg. Med. Chem. 15 (2007) 6678–6686
then washed with CH Cl (3 · 5 mL). The filtrate was
4.7. N-[4-Phenylazobenzoyl]-glutamyl-a-glutamic acid
(6e)
2
2
collected and the solvent removed under reduced pres-
sure to provide a reddish brown solid. The products
were purified by semi-preparative HPLC (Alltech
Semi-Prep Econosil C -10l, 250 · 22 mm) using a mo-
1
H NMR (300 MHz, DMSO-d ): d 1.81–2.10 (m, 4H),
6
2.30–2.40 (m, 4H), 4.20–4.27 (m, 1H), 4.47–4.54 (m,
1H), 7.62–7.65 (m, 3H), 7.94–7.98 (m, 4H), 8.11 (d,
2H, J = 9), 8.29 (d, 1H, J = 7.7), 8.67 (d, 1H, J = 7.7).
1
8
bile phase composed of 65% A and 35% B (Solvent
A = 0.1% aqueous TFA by volume; solvent
B = CH CN) to give the final products in typically
1
3
C NMR (75 MHz, DMSO-d ): d 26.2, 27.0, 30.1,
3
6
between 10% and 30% yield.
30.5, 51.2, 52.8, 122.3, 122.7, 128.4, 128.9, 129.6,
32.0, 136.2, 151.9, 153.3, 165.7, 171.4, 173.1, 173.8,
174.1.
1
4.3. N-[4-Phenylazobenzoyl]-glutamyl-c-glutamic acid
6a)
(
4
(6f)
.8. N-[4-Phenylazobenzoyl]–c-glutamyl-c-glutamic acid
1
Mp 181–182 ꢁC. H NMR (300 MHz, D O): d 1.79–1.93
2
(
(
m, 2H), 1.96–2.12 (m, 2H), 2.14–2.24 (m, 2H), 2.38–2.45
m, 2H), 4.05–4.09 (m, 1H), 4.27–4.31 (m, 1H), 7.49 (d,
1
H NMR (300 MHz, DMSO-d ): d 1.66–1.80 (m, 1H),
6
2
H, J = 6.6), 7.64–7.68 (m, 5H), 7.80 (d, 2H, J = 8.40).
C NMR (75 MHz, D O): d 28.76, 29.52, 33.37, 35.04,
6.24, 56.46, 123.36, 123.49, 129.28, 130.36, 133.07,
1.90–2.00 (m, 2H), 2.07–2.13 (m, 1H), 2.23–2.32 (m,
4H), 4.15–4.22 (m, 1H), 4. 35–4.42 (m, 1H), 7.60–7.64
1
3
2
5
1
1
(m, 3H), 7.92–7.98 (m, 4H), 8.09 (d, 2H, J = 9), 8.17
(d, 1H, J = 6), 8.87 (d, 1H, J = 6).
1
3
36.46, 152.75, 154.66, 169.61, 175.82, 178.88, 179.65,
82.94. lmax = 325 nm, e = 2.58 · 10 M cm
C NMR
(75 MHz, DMSO-d ): d 26.3, 30.1, 31.9, 51.2, 52.6,
4
ꢀ1
ꢀ1
.
6
122.4, 122.8, 128.8, 129.6, 132.1, 136.2, 151.9, 153.4,
165.7, 170.3, 171.8, 173.3, 173.7.
4
.4. N-[1-Pyrenebutyrl]-glutamyl-c-glutamic acid (6b)
1
H NMR (400 MHz, CD OD): d 1.11–1.17 (t, 2H),
4.9. N-[4-Phenylazobenzoyl]-D-glutamyl-a-glutamic acid
(6g)
3
1
(
(
.23–1.31 (m, 2H), 1.50 (s, 2H), 1.55 (s, 2H), 2.04–2.19
m, 2H), 2.34–2.43 (m, 2H), 3.36–3.40 (m, 2H), 3.87
m, 1H), 4.39–4.40 (m, 1H), 4.74–4.86 (m, 5H), 6.90–
1
H NMR (300 MHz, DMSO-d ): d 1.77–1.84 (m, 2H),
6
1
3
8
2
1
1
1
.36 (m, 9H). C NMR (75 MHz, DMSO-d ): d 6.3,
1.90–2.05 (m, 2H), 2.24–2.37 (m, 4H), 4.20–4.25 (m,
1H), 4.50–4.56 (m, 1H), 7.61–7.65 (m, 3H), 7.93–7.98
(m, 4H), 8.12 (d, 2H, J = 6), 8.26 (d, 1H, J = 6), 8.66
6
6.7, 27.6, 30.1, 31.6, 32.1, 34.7, 51.1, 51.6, 123.6,
24.1, 124.2, 124.8, 125.0, 126.1, 126.5, 127.2, 127.4,
27.6, 128.2, 129.3, 130.4, 130.9, 136.6, 171.6, 172.2,
73.4, 173.6, 173.7. HRMS (MALDI–TOF, positive
1
3
(d, 1H, J = 6). C NMR (75 MHz, DMSO-d ): d 26.5,
6
27.2, 30.1, 30.5, 51.3, 53.0, 122.3, 122.7, 129.9, 129.6,
132.0, 136.3, 151.9, 153.4, 165.7, 171.3, 173.1, 173.8,
174.0.
mode) Calcd [M+1] = 547.2080, found [M+1] =
5
47.2062 for C H N O .
30 30 2 8
4.5. N-[9-Anthracenyl]-aminobutyrl-glutamyl-c-glutamic
acid (6c)
4.10. N-[4-Phenylazobenzoyl]-aspartyl-a-glutamic acid
(6h)
1
1
H NMR (400 MHz, CD OD): d 1.88–1.97 (m, 2H),
H NMR (300 MHz, DMSO-d ): d 1.75–1.84 (m, 1H),
3
6
2
.07–2.16 (m, 2H), 2.14–2.23 (m, 2H), 2.35–2.41 (m,
H), 2.46–2.49 (m, 2H), 3.64–3.68 (m, 1H), 4.38–4.44
1.95–2.02 (m, 1H), 2.30 (t, 2H, J = 7.6), 2.67–2.84 (m,
2H), 4.21–4.25 (m, 1H), 4.82–4.87 (m, 1H), 7.62–7.67
(m, 3H), 7.93–7.99 (m, 4H), 8.09 (d, 2H, J = 9), 8.25
4
(
(
1
3
m, 2H), 4.86 (s, 6H), 7.48–8.57 (m, 9H). C NMR
1
3
75 MHz, DMSO-d ): d 25.5, 26.3, 27.0, 30.1, 31.6,
(d, 1H, J = 7.8), 8.86 (d, 1H, J = 7).
C NMR
6
3
1
1
2.8, 51.1, 51.6, 125.3, 125.6, 126.5, 127.1, 127.3,
28.4, 130.7, 133.4, 168.1, 171.6, 172.0, 173.4, 173.5,
73.7. LRMS (MALDI–TOF, positive mode, CD OD)
3
(75 MHz, DMSO-d ): d 26.0, 30.0, 36.0, 50.2, 51.3,
120.0, 122.3, 122.8, 128.9, 129.6, 132.1, 136.2, 151.9,
153.4, 165.5, 170.9, 171.8, 173.1, 173.8.
6
Calcd [M+1] = 566.2, found [M+1] = 566.9 (plus two
other deuteration states: 567.9 and 568.9) for
C H N O .
4.11. N-[4-Phenylazobenzoyl]-aspartyl–b-glutamic acid
(6i)
2
9
31
3
9
1
4
(
.6. N-[4-Nitrophenylbutyryl]-glutamyl-c-glutamic acid
6d)
H NMR (500 MHz, CD OD): d 1.83–1.89 (m, 1H),
3
2.09–2.16 (m, 1H), 2.27–2.38 (m, 2H), 4.40–4.55 (m,
H), 4.91–4.95 (m, 1H), 7.45–7.51 (m, 2H), 7.81–7.97
1
1
13
H NMR (400 MHz, CD OD): d 1.88–2.01 (m, 4H),
(m, 7H). C NMR (125 MHz, CD OD ): d 28.0, 31.2,
3
3
2
2
2
.10–2.24 (m, 4H), 2.26–2.27 (m, 2H), 2.27–2.40 (m,
H), 2.79 (t, 2H, J = 12), 4.37–4.45 (m, 2H), 7.46 (d,
H, J = 8), 8.15 (d, 2H, J = 8). C NMR (75 MHz,
38.1, 51.4, 53.0, 123.9, 124.2, 129.8, 130.5, 133.0,
137.3, 154.1, 155.9, 169.2, 172.7, 174.2, 174.9, 176.4.
1
3
CD OD): d 25.4, 28.0, 28.2, 28.4, 31.4, 33.3, 36.0, 36.1,
4.12. N-[4-Phenylazobenzoyl]-D-aspartyl-a-glutamic acid
(6j)
3
5
1
3.2, 53.4, 124.6, 124.7, 130.8, 148.0, 151.5, 175.0,
75.1, 175.9, 176.4. LRMS (ESI-LCMS, positive mode)
1
Calcd [M+1] = 468.16, found [M+1] = 468.17 for
C H N O .
H NMR (500 MHz, DMSO-d ): d 1.97–2.02 (m, 1H),
6
2.14–2.24 (m, 1H), 2.34–2.42 (m, 2H), 2.78–2.86 (dd,
2
0
25
3
10