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KALITA ET AL.
(d, J = 7.9 Hz, 1H), 6.12 (s, 1H), 4.60 (t, J = 10.3 Hz, 1H), 4.11 to 3.99
(m, 2H), 3.80 (t, J = 6.6 Hz, 1H), 3.47 (dd, J = 14.2, 3.3 Hz, 1H), 3.29 to
3.19 (m, 1H), 3.15 to 3.08 (m, 1H), 2.87 to 2.79 (m, 1H), 2.17 (s, 2H),
1.82 (s, 2H), 1.60 to 1.57 (m, 1H), 1.53 (s, 3H), 1.46 (s, 9H), 1.40 (s,
3H), 1.17 (d, J = 6.5 Hz, 3H), 1.12 (d, J = 6.5 Hz, 3H), 0.83 (d,
J = 6.4 Hz, 3H), 0.77 (d, J = 6.5 Hz, 3H); 13C NMR (125 MHz, CDCl3)
δ 200.0, 175.0, 172.7, 172.4, 170.6, 156.9, 138.7, 136.3, 133.8, 129.3,
128.8, 128.1, 126.1, 81.2, 57.3, 56.7, 54.6, 53.9, 41.5, 39.6, 37.0, 35.3,
28.2, 27.7, 24.9, 23.5, 23.0, 22.6, 22.4, 20.9; HRMS (ESI): m/z calcd for
3.94 (m, 2H), 3.37 (d, J = 13.0 Hz, 1H), 3.25 (d, J = 7.7 Hz, 2H), 3.07
to 3.00 (m, 1H), 2.38 (s, 2H), 2.23 (d, J = 6.0 Hz, 2H), 1.78 (s, 4H),
1.62 (t, J = 7.3 Hz, 1H), 1.46 (s, 10H), 1.36 (s, 3H), 1.24 (s, 3H), 1.18
(s, 6H), 1.09 to 1.04 (m, 5H), 1.00 (d, J = 6.7 Hz, 2H), 0.95 to 0.87
(m, 17H); 13C NMR (125 MHz, CDCl3) δ 199.7, 176.4, 174.2, 173.8,
172.9, 172.5, 172.3, 170.9, 157.2, 138.0, 136.5, 133.6, 129.1, 128.7,
128.4, 128.1, 126.6, 81.1, 61.0, 59.4, 57.3, 56.8, 54.7, 53.9, 41.4,
40.0, 39.6, 36.6, 35.2, 29.7, 29.7, 28.2, 26.7, 25.4, 23.5, 23.0, 22.7,
22.4, 21.17, 19.4, 19.1, 18.1, 17.9; HRMS (ESI): m/z calcd for
C
38H56N5O7 [M + H]+: 694.4180, found: 694.4177.
C
54H85N8O10 [M + H]+: 1005.6389, found: 1005.6397.
Boc‐δOPhe‐Aib‐Aib‐Leu‐Phe‐NHiPr (3)
Boc‐εOPhe‐Val‐Aib‐Leu‐Val‐NHiPr (6)
Column chromatography (petroleum ether/EtOAc, 20:80); white solid
Column chromatography (petroleum ether/EtOAc, 20:80); white solid
(0.350 g, 70%); mp 122 °C; IR (KBr)
͞
(0.300 g, 80%); mp 220 °C; IR (KBr) ͞ν
max (cm−1): 3312, 2964, 1662 (br),
1686, 1695, 1660,1644, 1540, 1465, 1268; 1H NMR (500 MHz,
CDCl3): δ 7.96 (d, J = 8.3 Hz, 2H), 7.61 (t, J = 7.3 Hz, 1H), 7.48
(dd, J = 15.1, 7.2 Hz, 5H), 7.27 (d, J = 6.8 Hz, 3H), 7.15 (t, J = 7.5 Hz,
2H), 7.07 (t, J = 7.3 Hz, 1H), 6.97 (d, J = 7.8 Hz, 1H), 6.85 (s, 1H), 6.17
(s, 1H), 4.72 to 4.60 (m, 1H), 4.06 to 4.03 (m, 2H), 3.83 (s, 1H), 3.55
(d, J = 14.5 Hz, 1H), 3.31 to 3.26 (m, 1H), 3.18 to 3.14 (m, 1H), 2.93
to 2.87 (m, 1H), 2.19 to 2.16 (m, 2H), 1.61 to 1.55 (m, 1H), 1.67
(s, 1H), 1.53 (s, 3H), 1.47 (s, 10H), 1.41 (s, 3H), 1.38 (s, 3H), 1.25
(s, 3H), 1.18 (t, J = 6.4 Hz, 6H), 0.87 (d, J = 6.4 Hz, 3H), 0.80
(d, J = 6.6 Hz, 3H); 13C NMR (125 MHz, CDCl3): δ 199.9, 176.1,
174.4, 173.1, 172.5, 170.8, 156.8, 138.9, 136.2, 133.9, 129.2, 129.0,
128.1, 126.0, 81.3, 57.3, 57.0, 56.7, 54.5, 54.2, 41.6, 39.2, 38.7,
37.1, 35.3, 29.7, 28.3, 27.6, 25.0, 23.2, 22.6, 22.3, 20.9; HRMS (ESI):
m/z calcd for C42H63N6O8 [M + H]+: 779.4707, found: 779.4698.
1531, 1467, 1450, 1336, 1254, 1171; 1H NMR (500 MHz, CDCl3):
δ 7.95 (d, J = 7.5 Hz, 2H), 7.65 (s, 1H), 7.60 (t, J = 7.4 Hz, 1H), 7.48
(t, J = 7.7 Hz, 2H), 7.25 (d, J = 6.6 Hz, 1H), 7.18 (d, J = 5.5 Hz, 1H),
6.78 (d, J = 7.7 Hz, 1H), 6.72 (s, 1H), 5.89 (s, 1H), 4.54 to 4.43
(m, 1H), 4.18 to 4.14 (m, 1H), 4.08 to 4.04 (m, 1H), 3.91 (s, 1H), 3.86
(s, 1H), 3.09 (t, J = 6.0 Hz, 2H), 2.48 (s, 1H), 2.17 (m, 1H), 1.90 to
1.85 (m, 2H), 1.75 (s br, 4H), 1.56 (s, 3H), 1.50 (s, 10H), 1.44 (s, 3H),
1.18 (d, J = 6.5 Hz, 3H), 1.14 (d, J = 6.6 Hz, 3H), 0.99 (d, J = 6.9 Hz,
6H), 0.96 (d, J = 6.6 Hz, 6H), 0.93 (d, J = 6.9 Hz, 3H), 0.89 (d, J = 5.8 Hz,
3H);13C NMR (125 MHz, CDCl3): δ 200.0, 175.6, 174.2, 173.67,
171.1, 170.9, 137.1, 133.5, 128.8, 128.1, 81.3, 61.1, 58.9, 57.2,
56.9, 54.1, 41.3, 40.1, 37.4, 30.4, 29.6, 29.1, 28.3, 27.4, 25.3, 23.4,
22.6, 22.2, 20.8, 19.8, 19.5, 18.8, 18.5, 17.6; HRMS (ESI): m/z calcd
for C40H67N6O8 [M + H]+: 759.5020, found: 759.5022.
Boc‐δOPhe‐Aib‐Phe‐Leu‐Val‐NHiPr (4)
Column chromatography (petroleum ether/EtOAc, 20:80); white solid
(0.320 g, 82%); mp 190 °C; IR (KBr) ͞ν
max (cm−1): 3319, 2968, 1661 (br),
|
4.4
X‐ray diffraction
1531, 1467, 1450, 1336, 1254, 1171; 1H NMR (500 MHz, CDCl3)
δ 7.95 (d, J = 7.8 Hz, 2H), 7.66 (s, 1H), 7.59 (t, J = 7.1 Hz, 1H), 7.47
(t, J = 7.6 Hz, 2H), 7.25 (t, J = 7.3 Hz, 3H), 7.19 (d, J = 7.5 Hz, 3H),
7.09 (s, 1H), 6.83 (s, 1H), 6.62 (s, 1H), 6.07 (s, 1H), 4.48 to 4.43
(m, 1H), 4.33 to 4.26 (m, 2H), 4.03 (dd, J = 13.4, 6.7 Hz, 1H), 3.86 to
3.82 (m, 1H), 3.37 (d, J = 12.9 Hz, 1H), 3.25 to 3.20 (m, 1H), 3.14
(s, 1H), 3.09 to 3.01 (m, 1H), 2.40 (s, 1H), 2.12 to 2.07 (m, 2H), 1.88
to 1.78 (m, 2H), 1.67 (s, 1H), 1.44 (s, 3H), 1.33 (s, 9H), 1.28 (s, 3H),
1.15 (t, J = 6.1 Hz, 6H), 0.95 to 0.98 (m, 12H); 13C NMR (125 MHz,
CDCl3) δ 200.0, 175.2, 173.2, 172.8, 170.4, 156.6, 137.1, 136.2,
133.9, 128.9, 128.7, 128.4, 128.1, 126.9, 81.2, 58.8, 56.8, 56.4,
55.9, 53.8, 39.7, 38.7, 36.3, 35.3, 29.2, 28.2, 25.0, 23.5, 22.7, 22.5,
21.0, 19.5, 17.4; HRMS (ESI): m/z calcd for C43H65N6O8 [M + H]+:
793.4864, found: 793.4868.
Single crystals of the peptides were grown by slow evaporation from
solutions in methanol‐water, acetonitrile‐water, or methanol‐
dichloromethane. Crystallization of peptide 4 yielded two polymorphic
forms (4a and 4b) in the triclinic space group P1 with different unit cell
parameters. 4a and 6 crystallized with two independent peptide mol-
ecules in the asymmetric unit, while 1, 4a, 4b, and
5 have
cocrystallized solvent molecules in their asymmetric units. X‐ray
diffraction data were collected at 293 K on a Bruker SMART APEX
CCD diffractometer (Billerica, Massachusetts) using graphite
monochromated MoKα radiation (λ = 0.71073 Å). Data were acquired
using a combination of ϕ and ω scans. The structures were solved by
direct methods using SHELXS24 (peptides 3, 4b, and 6) or SHELXD25
(peptides 1, 2, 4a, and 5) and were refined against F2 with full‐matrix
least squares method by using SHELXL‐2014 program.26 Anisotropic
refinement was performed on all the nonhydrogen atoms. A partially
occupied water molecule (occupancy 0.24) in 4b was isotropically
refined. Atoms C6G, C6D1, and C6D2 of the Leu6 side chain in 5
showed positional disorder, which was refined with an occupancy
ratio 0.63:0.37. Hydrogen atoms of the water molecule in 1 and the
amide hydrogen atom bonded to N1 in peptide 2 were located from
the electron density maps and were refined isotropically. All the other
hydrogen atoms were geometrically fixed and were refined as riding
over the atoms to which they are bonded. The details of crystallization
Boc‐δOPhe‐Val‐Leu‐Aib‐Phe‐Leu‐Val‐NHiPr (5)
Column chromatography (DCM/MeOH, 95:05); white solid (0.320 g,
60%); mp 190 °C; IR (KBr) ͞
νmax (cm−1): 3361, 2978, 1641 (br), 1531,
1467, 1450, 1336, 1254, 1171; 1H NMR (500 MHz, CDCl3) δ 7.93
(d, J = 7.4 Hz, 2H), 7.74 to 7.68 (m, 1H), 7.58 (t, J = 7.2 Hz, 1H),
7.45 (s, 3H), 7.38 (d, J = 6.9 Hz, 2H), 7.28 to 7.24 (m, 3H), 7.22 to
7.14 (m, 2H), 7.12 (d, J = 5.6 Hz, 1H), 6.97 to 6.86 (m, 2H), 6.76 to
6.70 (m, 1H), 6.33 (s, 1H), 4.37 to 4.27 (m, 3H), 4.05 (s, 2H), 3.98 to