Page 9 of 12
Organic & Biomolecular Chemistry
Please do not adjust margins
Journal Name
ARTICLE
11Pro4b), 1.58 – 1.40 (m, 3Pip3b, 3Pip4a, 3Pip5a, 10Ile4a), 1Asp2, 5Asp2, 7Asp2), 4.35 (m, 3Pip6a), 4.31 – 4.24 (m, 9Thr2,
1.39 – 1.36 (m, FA5, 3Pip4b), 1.28 – 1.23 (m, FA6‐13, 3Pip5b), 10Ile2), 4.19 (m, 11Pro2), 3.98 (dd, J =D1O6I.:91,0.610.039H/Cz8,O4BG0l1y226a8G),
1.06 – 1.00 (m, 9Thr4, 10Ile4b), 0.87 – 0.83 (m, FA14, 3.85 – 3.64 (m, 4Gly2b, 6Gly2, 8Gly2, 9Thr3, 11Pro5a), 3.57 –
10Ile3Me), 0.78 (t, J = 7.3 Hz, 10Ile5) ppm.
3.50 (m, 2Dap3a, 11Pro5b), 3.15 (m, 2Dap3b), 2.85 (m,
(
E
)‐Dodec‐2‐enoyl derivative (22): Prepared on a 20.0 mg 3Pip6b), 2.70 – 2.51 (m, 1Asp3a, 5Asp3, 7Asp3), 2.44 (dd, J =
(11.0 μmol) scale and purified with 20‐100% B over 45 min. 16.4, 7.8 Hz, 1Asp3b), 2.19 (m, 3Pip3a), 2.09 (m, FA2), 2.01 (m,
Yield = 7.2 mg, 54% (2 steps). Analytical HPLC Rt = 3.4 min. 11Pro3a), 1.93 (m, 11Pro4a), 1.83 – 1.72 (m, 10Ile3, 11Pro3b,
LRMS (ESI+) 1205 [M+H]+, 1227 [M+Na]+. HRMS (ESI+) calcd 11Pro4b), 1.62 – 1.33 (m, FA3, 3Pip3b, 3Pip4, 3Pip5a, 10Ile4a),
for C54H84N12O19Na [M+Na]+ 1227.5870, found 1227.5880. 1H 1.29 – 1.23 (m, FA4‐13, 3Pip5b), 1.08 – 1.01 (m, 9Thr4,
NMR (500 MHz, DMSO‐d6) major rotamer δ 8.34 (d, J = 7.4 Hz, 10Ile4b), 0.87 – 0.84 (m, FA14, 10Ile3Me), 0.78 (m, J = 7.4 Hz)
7Asp2NH), 8.27 (d, J = 7.5 Hz, 5Asp2NH), 8.23 (d, J = 7.7 Hz, ppm.
2Dap2NH), 8.15 – 8.07 (m, 1Asp2NH, 4Gly2NH, 6Gly2NH), 7.92 Dodecanoyl derivative (25): Prepared on a 20.0 mg (11.0
(m, 8Gly2NH), 7.85 (d, J = 7.9 Hz, 9Thr2NH), 7.68 (m, μmol) scale and purified with 20‐100% B over 45 min. Yield =
10Ile2NH), 7.50 (m, 2Dap3NH), 6.63 (dt, J = 15.2, 6.8 Hz, FA3), 8.7 mg, 65% (2 steps). Analytical HPLC Rt = 3.5 min. LRMS
5.91 (d, J = 15.3 Hz, FA2), 4.79 (m, 3Pip2), 4.68 – 4.55 (m,
(
ESI+) 1207 [M+H]+, 1229 [M+Na]+. HRMS (ESI+) calcd for
1Asp2, 2Dap2, 5Asp2), 4.48 (m, 7Asp2), 4.35 – 4.25 (m, 3Pip6a, C54H86N12O19Na [M+Na]+ 1229.6024, found 1229.6014. 1H NMR
9Thr2, 10Ile2), 4.18 (dd, J = 6.6, 5.2 Hz, 11Pro2), 3.96 (m, (600 MHz, DMSO‐d6) major rotamer δ 8.33 (d, J = 7.1 Hz,
4Gly2a), 3.84 – 3.50 (m, 2Dap3a, 4Gly2b, 6Gly2, 8Gly2, 9Thr3, 7Asp2NH), 8.25 (d, J = 7.9 Hz, 5Asp2NH), 8.14 – 8.12 (m,
11Pro5), 3.13 (m, 2Dap3b), 2.86 (m, 3Pip6b), 2.74 (dd, J = 16.4, 2Dap2NH, 6Gly2NH), 8.07 (m, 4Gly2NH), 8.03 (d, J = 7.8 Hz,
5.4 Hz, 5Asp3a), 2.70 (dd, J = 16.6, 4.7 Hz, 7Asp3a), 2.63 (dd, J 1Asp2NH), 7.88 – 7.87 (m, 8Gly2NH, 9Thr2NH), 7.74 (d, J = 8.4
= 16.4, 5.5 Hz, 1Asp3a), 2.55 – 2.46 (m, 1Asp3b, 5Asp3b, Hz, 10Ile2NH), 7.51 (m, 2Dap3NH), 4.79 (m, 3Pip2), 4.66 (m,
7Asp3b), 2.17 (m, 3Pip3a), 2.12 (m, FA4), 2.00 (m, 11Pro3a), 2Dap2), 4.60 – 4.49 (m, 5Asp2, 1Asp2, 7Asp2), 4.36 (m,
1.91 (m, 11Pro4a), 1.83 – 1.69 (m, 10Ile3, 11Pro3b, 11Pro4b), 3Pip6a), 4.29 (m, 9Thr2, 10Ile2), 4.19 (m, 11Pro2), 3.99 (dd, J =
1.59 – 1.47 (m, 3Pip3b, 3Pip4a, 3Pip5a, 10Ile4a), 1.39 – 1.36 16.6, 6.5 Hz, 4Gly2a), 3.81 – 3.64 (m, 4Gly2b, 6Gly2, 8Gly2,
(m, FA5, 3Pip4b), 1.27 – 1.23 (m, FA6, FA7, FA8, FA9, FA10, 9Thr3, 11Pro5a), 3.56 – 3.51 (m, 2Dap3a, 11Pro5b), 3.10 (m,
FA11, 3Pip5b), 1.06 – 1.00 (m, 9Thr4, 10Ile4b), 0.89 – 0.83 (m, 2Dap3b), 2.86 (m, 3Pip6b), 2.75 – 2.53 (m, 1Asp3a, 5Asp3,
FA12, 10Ile3Me), 0.77 (t, J = 7.4 Hz) ppm.
7Asp3), 2.44 (dd, J = 16.3, 8.0 Hz, 1Asp3b), 2.19 (m, 3Pip3a),
(
E)‐But‐2‐enoyl derivative (23): Prepared on a 20.0 mg (11.0 2.09 (m, FA2), 2.02 (m, 11Pro3a), 1.94 (m, 11Pro4a), 1.84 –
μmol) scale and purified with 0‐100% B over 45 min. Yield = 6.8 1.70 (m, 11Pro4b, 10Ile3, 11Pro3b), 1.58 – 1.32 (m, 3Pip3b,
mg, 56% (2 steps). Analytical HPLC Rt = 2.1 min. LRMS (ESI+) 3Pip4, 3Pip5a, 10Ile4a, FA3), 1.28 – 1.23 (m, 3Pip5b, FA4‐
1093 [M+H]+, 1115 [M+Na]+. HRMS (ESI+) calcd for FA11), 1.06 – 1.00 (m, 9Thr4, 10Ile4b), 0.90 – 0.84 (m, FA12,
C46H68N12O19Na [M+Na]+ 1115.4616, found 1115.4602. 1H NMR 10Ile3Me), 0.78 (m, 10Ile5) ppm.
(500 MHz, DMSO‐d6) δ 8.34 (d, J = 7.3 Hz, 7Asp2NH), 8.26 (d, J Decanoyl derivative (26): Prepared on a 20.0 mg (11.0 μmol)
= 7.7 Hz, 5Asp2NH), 8.22 (d, J = 7.6 Hz, 2Dap2NH), 8.14 – 8.07 scale and purified with 20‐100% B over 45 min. Yield = 8.9 mg,
(m, 1Asp2NH, 4Gly2NH, 6Gly2NH), 7.91 (m, 8Gly2NH), 7.86 (d, 68% (2 steps). Analytical HPLC Rt = 3.1 min. LRMS (ESI+) 1179
J = 8.5 Hz, 9Thr2NH), 7.70 (d, J = 8.4 Hz, 10Ile2NH), 7.49 (m, [M+H]+, 1201 [M+Na]+. HRMS (ESI+) calcd for C52H82N12O19Na
2Dap3NH), 6.63 (m, FA3), 5.94 (m, FA2), 4.80 (m, 3Pip2), 4.68 – [M+Na]+ 1201.5711, found 1201.5691. 1H NMR (500 MHz,
4.56 (m, 1Asp2, 2Dap2, 5Asp2), 4.49 (m, 7Asp2), 4.36 – 4.26 DMSO‐d6) major rotamer δ 8.33 (d, J = 7.1 Hz, 7Asp2NH), 8.25
(m, 3Pip6a, 9Thr2, 10Ile2), 4.18 (dd, J = 7.4, 6.1 Hz, 11Pro2), (d, J = 7.9 Hz, 5Asp2NH), 8.12 – 8.11 (m, 2Dap2NH, 6Gly2NH),
3.97 (dd, J = 16.5, 6.6 Hz, 4Gly2a), 3.84 – 3.49 (m, 2Dap3a, 8.06 (m, 4Gly2NH), 8.02 (d, J = 7.8 Hz, 1Asp2NH), 7.90 (m,
4Gly2b, 6Gly2, 8Gly2, 9Thr3, 11Pro5), 3.12 (m, 2Dap3b), 2.86 8Gly2NH), 7.86 (d, J = 8.5 Hz, 9Thr2NH), 7.70 (d, J = 8.4 Hz,
(m, 3Pip6b), 2.77 – 2.46 (m, 1Asp3, 5Asp3, 7Asp3), 2.17 (m, 10Ile2NH), 7.51 (m, 2Dap3NH), 4.78 (m, 3Pip2), 4.66 (m,
3Pip3a), 2.01 (m, 11Pro3a), 1.92 (m, 11Pro4a), 1.83 – 1.68 (m, 2Dap2), 4.61 – 4.47 (m, 1Asp2, 5Asp2, 7Asp2), 4.36 – 4.26 (m,
10Ile3, 11Pro3b, 11Pro4b, FA4), 1.59 – 1.48 (m, 3Pip3b, 3Pip6a, 9Thr2, 10Ile2), 4.19 (dd, J = 8.0, 5.8 Hz, 11Pro2), 3.98
3Pip4a, 3Pip5a, 10Ile4a), 1.39 (m, 3Pip4b), 1.23 (m, 3Pip5b), (dd, J = 16.6, 6.7 Hz, 4Gly2a), 3.84 – 3.74 (m, 6Gly2, 8Gly2,
1.07 – 1.00 (m, 9Thr4, 10Ile4b), 0.87 (d, J = 6.7 Hz, 10Ile3Me), 9Thr3, 11Pro5a), 3.66 (dd, J = 15.6, 4.5 Hz, 4Gly2b), 3.53 (m,
0.78 (t, J = 7.4 Hz, 10Ile5) ppm.
2Dap3a, 11Pro5b), 3.11 (m, 2Dap3b), 2.86 (m, 3Pip6b), 2.76 –
Tetradecanoyl derivative (24): Prepared on a 20.0 mg (11.0 2.52 (m, 1Asp3a, 5Asp3, 7Asp3), 2.44 (dd, J = 16.5, 7.9 Hz,
μmol) scale and purified with 20‐100% B over 45 min. Yield = 1Asp3b), 2.18 (m, 3Pip3a), 2.09 (m, FA2), 2.02 (m, 11Pro3a),
7.6 mg, 56% (2 steps). Analytical HPLC Rt = 3.9 min. LRMS 1.94 (m, 11Pro4a), 1.83 – 1.70 (m, 10Ile3, 11Pro3b, 11Pro4b),
(
ESI+) 1235 [M+H]+, 1257 [M+Na]+. HRMS (ESI+) calcd for 1.59 – 1.32 (m, FA3, 3Pip3b, 3Pip4, 3Pip5a, 10Ile4a), 1.28 –
C56H90N12O19Na [M+Na]+ 1257.6337, found 1257.6338. 1H NMR 1.23 (m, FA4‐9, 3Pip5b), 1.07 – 1.00 (m, 9Thr4, 10Ile4b), 0.87 –
(600 MHz, DMSO‐d6) major rotamer δ 8.37 (m, 7Asp2NH), 8.22 0.83 (m, FA10, 10Ile3Me), 0.78 (t, J = 7.5 Hz, 10Ile5) ppm.
– 8.18 (m, 5Asp2NH, 6Gly2NH), 8.14 (d, J = 7.5 Hz, 2Dap2NH), Hexanoyl derivative (27): Prepared on a 20.0 mg (11.0 μmol)
8.07 (m, 4Gly2NH), 8.03 (d, J = 7.9 Hz, 1Asp2NH), 7.96 – 7.91 scale and purified with 0‐100% B over 45 min. Yield = 8.0 mg,
(m, 8Gly2NH, 9Thr2NH), 7.77 (m, 10Ile2NH), 7.52 (m, 64% (2 steps). Analytical HPLC Rt = 2.4 min. LRMS (ESI+) 1123
2Dap3NH), 4.78 (m, 3Pip2), 4.65 (m, 2Dap2), 4.59 – 4.45 (m, [M+H]+, 1145 [M+Na]+. HRMS (ESI+) calcd for C48H74N12O19Na
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1‐3 | 9
Please do not adjust margins