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B. Gadakh et al. / Bioorg. Med. Chem. 22 (2014) 2875–2886
6.1.12.1. fMRTGNAI-S(4-nitrobenzimidazole) (17a).
(600 MHz, D2O) d 0.73 (t, 3H, J = 7.2 Hz, Ile-d-CH3), 0.81 (d, 3H,
J = 6.6 Hz, Ile- -CH3), 1.00–1.10 (m, 1H, Ile- -CH2, Ha), 1.14–1.21
(m, Thr- -CH3, TEA-CH3), 1.27–1.39 (d+m, 4H, J = 7.2 Hz, Ala-b-
CH3 and Ile- -CH2, Hb), 1.55 (m, 2H, Arg- -CH2), 1.67–1.88 (m,
3H, Ile b-CH and 2H, Arg-b-CH2), 1.95–2.07 (m+s, 5H, Met-b-CH2
and Met-SCH3), 2.53 (m, 2H, Met- -CH2), 2.37 (dd, 1H, J = 8.4 Hz
1H NMR
Asn-b-CH2, Hb), 3.11 (t, 2H, J = 6.6 Hz, Arg-d-CH2), 3.16 (q,
J = 7.8 Hz, TEA-CH2), 3.89 (d, 1H, J = 6.6 Hz and 16.6 Hz,
c
c
Gly-
4.18–4.24 (m, 1H, Thr-b-CH), 4.25–4.31 (m, 3H, H-50a and H-50b,
Ala- -CH), 4.33–4.37 (m, 2H, J = 4.4 Hz, Thr-
-CH, H-40), 4.37–
4.43 (m, 2H, Arg-
-CH, H-30), 4.49 (dd, 1H, J = 5.9 Hz and 8.2 Hz,
Met-a-CH), 4.66–4.72 (m, 2H, Asn-a
-CH and H-20), 5.89 (d, 1H,
a-CH2, Ha), 3.95–4.02 (m, 2H, Ile-a-CH and Gly-a-CH2, Hb),
c
c
c
a
a
a
c
and 15.6 Hz, Asn-b-CH2, Ha), 2.78 (dd, 1H, J = 4.8 Hz, and 16.2 Hz,
Asn-b-CH2, Hb), 3.00 (m, TEA-CH2), 3.10 (m, 2H, Arg-d-CH2), 3.87
J = 6.6 Hz, H-10), 8.00 (s, 1H, H-8), 8.08 (s, 1H, CHO). 13C NMR
(150 MHz, D2O) d 7.3 (TEA-CH3), 10.0 (Ile-d-CH3), 13.6 (Met-
(d, 1H, J = 16.9 Hz, Gly-
and Gly- -CH2, Hb), 4.19–4.28 (m, 2H, Thr-b-CH, Ala-
4.31–4.41 (m, 4H, Thr- -CH, Arg-
-CH and H-50a and H-50b),
4.42–4.46 (m, 2H, H-30and H-40), 4.49 (dd, 1H, J = 5.9 Hz and
a
-CH2, Ha), 3.94–4.00 (m, 2H, Ile-
a
-CH),
-CH
SCH3), 14.5 (Ile-
(Ile- -CH2), 23.9 (Arg-
29.8 (Met-b-CH2), 35.8 (Asn-b-CH2), 36.5 (Ile-b-CH), 40.1 (Arg-d-
CH2), 42.1 (Gly- -CH2), 46.0 (TEA-CH2), 49.5 (Ala- -CH), 49.9
(Asn- -CH), 51.1 (Met- -CH), 53.0 (Arg- -CH), 58.6 (Thr- -CH),
60.2 (Ile-
c
-CH3), 15.9 (Ala-b-CH3), 18.2 (Thr-
c
-CH3), 23.8
a
a
c
c
-CH2), 27.7 (Arg-b-CH2), 28.7 (Met-
c
-CH2),
a
a
a
a
8.2 Hz, Met-
a
-CH), 4.64–4.68 (m, 2H, H-20 and Asn-
a
-CH), 6.13
a
a
a
a
(d, 1H, J = 6.7 Hz, H-10), 7.54 (t, 1H, J = 8.3 Hz, H-6), 8.08 (s, 1H,
CHO), 8.16 (d, 1H, J = 8.3 Hz, H-7), 8.26 (d, 1H, J = 8.3 Hz, H-5),
8.68 (s, 1H, H-2). 13C NMR (150 MHz, D2O) d 8.9 (TEA-CH3), 10.1
a
-CH), 66.9 (Thr-b-CH), 68.1 (C-50), 70.0 (C-30), 73.1
(C-20), 82.0 (C-40), 85.9 (C-10), 116.2 (C-5), 136.3 (C-8), 151.4
(C-4), 156.0 (Arg-Cf), 163.7 (CHO), 170.6 (Gly-CO), 171.5
(Asn-CO), 171.7 (Thr-CO), 173.1 (Met-CO), 173.2 (Arg-CO), 173.7
(Ile-d-CH3), 13.8 (Met-SCH3), 14.7 (Ile-
18.3 (Thr- -CH3), 24.0 (Ile- -CH2), 24.1 (Arg-
CH2), 28.7 (Met- -CH2), 30.1 (Met-b-CH2), 35.9 (Asn-b-CH2), 36.6
(Ile-b-CH), 40.1 (Arg-d-CH2), 42.2 (Gly- -CH2), 45.6 (TEA-CH2),
49.5 (Ala- -CH), 49.9 (Asn- -CH), 51.1 (Met- -CH), 53.0 (Arg-
CH), 58.6 (Thr- -CH), 60.2 (Ile-
-CH), 66.9 (Thr-b-CH), 68.0 (C-50),
c-CH3), 16.1 (Ala-b-CH3),
c
c
c
-CH2), 27.7 (Arg-b-
(Ala-CO), 173.8 (Asn-C
c), 179.1 (Ile-CO). HRMS for C41H66N17O17S2
c
([M-H]-) calcd: 1132.4269 found 1132.4274.
a
a
a
a
a
-
6.1.12.4. fMRTGNAI-SI (17d).
1H NMR (600 MHz, D2O) d 0.75
a
a
(t, 3H, J = 7.2 Hz, Ile-d-CH3), 0.81 (d, 3H, J = 6.6 Hz, Ile-c-CH3),
70.0 (C-30), 73.4 (C-20), 82.8 (C-40), 88.7 (C-10), 119.0 (C-7), 120.5
(C-5), 123.2 (C-6), 134.8 (C-8), 135.9 (C-9), 137.7 (C-4), 145.4 (C-
2), 156.2 (Arg-Cf), 163.9 (CHO), 170.9 (Gly-CO), 171.8 (Asn-CO),
172.0 (Thr-CO), 173.0 (Met-CO), 173.3 (Arg-CO), 174.0 (Ala-CO
1.04–1.10 (m, Ile-
-CH3),1.29–1.37 (d+m, 4H, J = 7.2 Hz, Ala-b-CH3 and Ile-
Ha), 1.55 (m, 2H, Arg- -CH2), 1.69–1.77 (m, 2H, Ile-b-CH and Arg-
b-CH2, Ha), 1.79–1.87 (m, 1H, Arg-b-CH2, Hb), 1.94–2.08 (m+s, 5H,
Met-b-CH2 and Met-SCH3), 2.45–2.57 (m, 2H, Met- -CH2), 2.67–
c-CH2, Ha, TEA-CH3), 1.16 (d, 3H, J = 6.3 Hz, Thr-
c
c-CH2,
c
and Asn-C
calcd: 1144.4158 found 1144.4150.
c
), 179.1 (Ile-CO). HRMS for C43H66N15O18S2 ([MꢁH]ꢁ)
c
2.76 (m, TEA-CH2 and Asn-b-CH2, Ha), 2.80 (dd, 1H, J = 4.8 Hz and
16.2 Hz, Asn-b-CH2, Hb), 3.10 (t, 2H, J = 6.6 Hz, Arg-d-CH2), 3.87 (d,
6.1.12.2. fMRTGNAI-SA (17b).
3H, J = 7.2 Hz, Ile-d-CH3), 0.90 (d, 3H, J = 6.6 Hz, Ile-
1H NMR (600 MHz, D2O) d 0.85 (t,
1H, J = 16.8 Hz, Gly-
Gly- -CH2, Hb), 4.18–4.24 (m, 1H, Thr-b-CH), 4.25–4.31 (m, 3H,
H-50a and H-50b, Ala-
-CH), 4.33 (d, 1H, J = 4.4 Hz, Thr- -CH),
4.36–4.43 (m, 3H, Arg-
-CH, H-30, H-40), 4.48 (dd, 1H, J = 5.9 Hz
and 8.2 Hz, Met-
a-CH2, Ha), 3.95–4.01 (m, 2H, Ile-a-CH and
c
-CH3), 1.13–
a
1.24 (m, Thr-
J = 7.2 Hz, Ala-b-CH3), 1.43–1.52 (m, 1H, Ile-
2H, Arg- -CH2), 1.71–1.92 (m, 3H, Ile b-CH and 2H, Arg-b-CH2),
1.96–2.08 (m+s, 5H, Met-b-CH2 and Met-SCH3), 2.55 (m, 2H, Met-
-CH2), 2.70 (dd, 1H, J = 8.4 Hz and 15.6 Hz, Asn-b-CH2, Ha), 2.79
(dd, 1H, J = 4.8 Hz, and 16.2 Hz, Asn-b-CH2, Hb), 3.08–3.21 (m,
TEA-CH2 and Arg-d-CH2), 3.97 (d, 1H, J = 16.9 Hz, Gly- -CH2, Ha),
3.98 (d, 1H, J = 16.9 Hz, Gly- -CH2, Hb), 4.06 (d, 1H, J = 6.9 Hz,
Ile- -CH), 4.21 (m, 1H, Thr-b-CH), 4.26–4.46 (m, 7H, Ala- -CH,
Thr- -CH, Arg-
-CH, H-30, H-40 and H-50a and H-50b), 4.50 (dd,
1H, J = 5.9 Hz, and 8.2 Hz, Met- -CH), 4.67 (dd, 1H, J = 5.2 Hz and
c-CH3, TEA-CH3 and Ile-
c-CH2, Ha), 1.36 (d, 3H,
a
a
c-CH2, Hb), 1.61 (m,
a
c
a-CH), 4.67–4.73 (m, 2H, Asn-a
-CH and H-20),
6.03 (d, 1H, J = 6.6 Hz, H-10), 8.08 (s, 1H, CHO), 8.11 (s, 1H, H-2),
c
8.25 (s, 1H, H-8). 13C NMR (150 MHz, D2O) d 9.1 (TEA-CH3), 10.1
(Ile-d-CH3), 13.8 (Met-SCH3), 14.7 (Ile-
18.4 (Thr- -CH3), 24.2 (Ile- -CH2 and Arg-
(Arg-b-CH2), 28.8 (Met- -CH2), 30.0 (Met-b-CH2), 35.9 (Asn-b-
CH2), 36.6 (Ile-b-CH), 40.0 (Arg-d-CH2), 42.2 (Gly- -CH2), 45.5
(TEA-CH2), 49.6 (Ala- -CH), 50.0 (Asn- -CH), 51.3 (Met- -CH),
53.2 (Arg- -CH), 58.8 (Thr- -CH), 60.4 (Ile- -CH), 66.9 (Thr-b-CH),
c-CH3), 16.1 (Ala-b-CH3),
a
c
c
c-CH2), 27.5
a
c
a
a
a
a
a
a
a
a
a
a
a
a
8.9 Hz, Asn-
a
-CH), 4.72 (m, 1H, H-20), 6.09 (d, 1H, J = 5.9 Hz, H-
68.2 (C-50), 70.3 (C-30), 73.5 (C-20), 82.2 (C-40), 86.1 (C-10), 123.0
(C-5), 137.3 (C-8), 149.8 (C-4), 153.6 (C-2), 156.2 (Arg-Cf), 164.0
(CHO), 167.3 (C-6), 170.9 (Gly-CO), 171.8 (Asn-CO), 172.1 (Thr-CO),
10), 8.08 (s, 1H, CHO), 8.22 (s, 1H, H-2), 8.42 (s, 1H, H-8). 13C
NMR (150 MHz, D2O) d 7.9 (TEA-CH3), 9.8 (Ile-d-CH3), 13.8 (Met-
SCH3), 14.4 (Ile-
(Ile- -CH2), 24.3 (Arg-
30.1 (Met-b-CH2), 35.4 (Asn-b-CH2), 35.9 (Ile-b-CH), 40.1 (Arg-d-
CH2), 42.1 (Gly- -CH2), 46.3 (TEA-CH2), 49.5 (Ala- -CH), 50.0
(Asn- -CH), 51.1 (Met- -CH), 53.2 (Arg- -CH), 58.8 (Thr- -CH),
60.4 (Ile-
c
-CH3), 16.0 (Ala-b-CH3), 18.4 (Thr-
c
-CH3), 24.1
173.3 (Met-CO), 173.6 (Arg-CO), 174.0 (Ala-CO), 174.1 (Asn-Cc),
c
c-CH2), 27.6 (Arg-b-CH2), 28.7 (Met-
c-CH2),
179.4 (Ile-CO). HRMS for
C
41H65N16O17S2 ([MꢁH]ꢁ) calcd:
1117.4160 found 1117.4186.
a
a
a
a
a
a
6.1.12.5. fMRTGNAI-SC (17e).
1H NMR (600 MHz, D2O) d 0.82
-CH3),
-CH3 and
TEA-CH3), 1.35 (d, 3H, J = 7.2 Hz, Ala-b-CH3), 1.37–1.44 (m, 1H,
Ile- -CH2, Hb), 1.61 (m, 2H, Arg- -CH2), 1.75 (m, 1H, Ile-b-CH),
1.84 (m, 2H, Arg-b-CH2), 1.96–2.09 (m+s, 5H, Met-b-CH2 and
Met-SCH3), 2.55 (m, 2H, Met- -CH2), 2.70 (m, 1H, Asn-b-CH2, Ha),
a
-CH), 66.9 (Thr-b-CH), 68.0 (C-50), 70.2 (C-30), 73.7 (C-
(t, 3H, J = 7.2 Hz, Ile-d-CH3), 0.88 (d, 3H, J = 6.6 Hz, Ile-
c
20), 82.8 (C-40), 86.5 (C-10), 139.4 (C-8), 148.8 (C-4), 152.7 (C-2),
155.2 (C-6), 156.4 (Arg-Cf), 163.9 (CHO), 170.9 (Gly-CO), 172.0
(Asn-CO and Thr-CO), 173.1 (Met-CO), 173.4 (Arg-CO), 174.0 (Ala-
1.07–1.15 (m, 1H, Ile- -CH2, Ha), 1.15–1.24 (m, Thr-
c
c
c
c
CO and Asn-Cc), 179.6 (Ile-CO). HRMS for C41H68N17O16S2
([MꢁH]ꢁ) calcd: 1116.4320 found 1116.4305.
c
2.80 (dd, 1H, J = 4.8 Hz and 16.2 Hz, Asn-b-CH2, Hb), 3.07 (m,
TEA-CH2), 3.16 (t, 2H, J = 6.6 Hz, Arg-d-CH2), 3.89 (d, 1H,
6.1.12.3. fMRTGNAI-SG (17c).
1H NMR (600 MHz, D2O) d 0.77 (t,
3H, J = 7.2 Hz, Ile-d-CH3), 0.82 (d, 3H, J = 6.6 Hz, Ile-
c
-CH3), 1.05 (m,
-CH3), 1.24 (t,
J = 3.6 Hz, TEA-CH3), 1.32 (d, 3H, J = 7.2 Hz, Ala-b-CH3), 1.36 (m,
1H, Ile- -CH2, Hb), 1.58 (m, 2H, Arg- -CH2), 1.69–1.89 (m, 3H, Ile
b-CH and Arg-b-CH2), 1.94–2.08 (m+s, 5H, Met-b-CH2 and Met-
SCH3), 2.45–2.57 (m, 2H, Met- -CH2), 2.70 (dd, 1H, J = 8.4 Hz and
15.6 Hz, Asn-b-CH2, Ha), 2.80 (dd, 1H, J = 4.8 Hz and 16.2 Hz,
J = 5.4 Hz, Gly-
Gly-
-CH2, Hb), 4.18–4.25 (m, 2H, H-20 and Thr-b-CH), 4.27–4.33
(m, 4H, H-50a, H-50b, H-30 and Ala-
-CH), 4.34–4.45 (m, 3H, Thr-
-CH, Arg-
-CH and H-40), 4.50 (dd, 1H, J = 5.9 Hz and 8.2 Hz,
Met-
a-CH2, Ha), 3.95–4.04 (m, 2H, Ile-a-CH and
1H, Ile-
c
-CH2, Ha), 1.16 (d, J = 6.3 Hz, 3H, Thr-
c
a
a
c
c
a
a
a
-CH), 4.68 (dd, 1H, J = 5.2 Hz and 8.9 Hz, Asn-a-CH), 5.92
c
(d, 1H, J = 3.2 Hz, H-10), 6.03 (d, 1H, J = 7.5 Hz, H-5), 7.82 (d, 1H,
J = 7.5 Hz, H-6), 8.09 (s, 1H, CHO). 13C NMR (150 MHz, D2O) d 8.3