Stephan Lepper, Lukas Biermann, Fabian B. Kraft, Felix Feller, Kathrin Tan, Nisha Setia, Emma Martens, Alexandra Hamacher, Linda Schäker-Hübner, Matthias U. Kassack, Finn K. Hansen. “Discovery of potent and non-cytotoxic HDAC3-selective degraders featuring a propyl hydrazide zinc-binding group.” ChemRxiv (). https://doi.org/10.26434/chemrxiv.15001540/v3

Benzyl 2-(4-{(S)-2-[4-(dimethylamino)benzoyl]-12-[(2S,4R)-4-hydroxy-2-{[4-(4-methylthiazol-5-yl)benzyl]carbamoyl}pyrrolidine-1-carbonyl]-13,13-dimethyl-4,10-dioxo-8-oxa-2,5,11-triazatetradecyl}benzoyl)-1-propylhydrazine-1-carboxylate trifluoroacetate
Identifier Cbz-1a
¹H NMR (500 MHz, DMSO-d₆) δ 10.72 – 10.59 (m, 1H), 9.01 – 8.95 (m, 1H), 8.60 – 8.50 (m, 1H), 8.12 (s, 1H), 7.83 (d, J = 8.5 Hz, 2H), 7.50 – 7.43 (m, 1H), 7.43 – 7.21 (m, 13H), 6.70 (d, J = 8.3 Hz, 2H), 5.20 – 5.03 (m, 2H), 4.66 (d, J = 6.1 Hz, 2H), 4.56 (d, J = 9.5 Hz, 1H), 4.48 – 4.42 (m, 1H), 4.39 – 4.31 (m, 2H), 4.29 – 4.22 (m, 1H), 4.03 – 3.92 (m, 2H), 3.90 – 3.81 (m, 2H), 3.70 – 3.57 (m, 2H), 3.55 – 3.41 (m, 4H), 3.37 – 3.22 (m, 2H), 2.93 (s, 6H), 2.44 (s, 3H), 2.09 – 2.00 (m, 1H), 1.96 – 1.85 (m, 1H), 1.55 (h, J = 7.3 Hz, 2H), 0.93 – 0.86 (m, 12H)
¹³C NMR (126 MHz, DMSO-d₆) δ 171.6, 171.6, 169.1, 168.5, 168.1, 165.3, 158.2 (d, J = 37.7 Hz), 155.7, 151.4, 151.0, 147.6, 141.7, 139.4, 136.6, 131.1, 129.6, 128.8, 128.6, 128.5, 128.2, 128.0, 127.7, 127.4, 127.0, 115.2 (d, J = 289.6 Hz), 111.2, 69.7, 69.6, 69.4, 68.8, 66.5, 58.7, 56.4, 55.8, 50.9, 41.7, 38.5, 37.8, 36.0, 35.6, 26.1, 20.2, 15.8, 11.1
LC-MS (ESI) m/z: [M+H]⁺ calcd for C₅₆H₆₉N₉O₁₀S: 1060.5, found: 1060.5
Main, p. 39
Benzyl 2-(4-{(S)-2-[4-(dimethylamino)benzoyl]-15-((2S,4R)-4-hydroxy-2-{[4-(4-methylthiazol-5-yl)benzyl]carbamoyl}pyrrolidine-1-carbonyl)-16,16-dimethyl-4,13-dioxo-8,11-dioxa-2,5,14-triazaheptadecyl}benzoyl)-1-propylhydrazine-1-carboxylate trifluoroacetate
Identifier Cbz-1b
¹H NMR (600 MHz, DMSO-d₆) δ 10.77 – 10.59 (m, 1H), 9.02 – 8.97 (m, 1H), 8.55 (t, J = 6.1 Hz, 1H), 7.83 (d, J = 8.8 Hz, 2H), 7.46 – 7.36 (m, 7H), 7.35 – 7.32 (m, 5H), 7.31 – 7.21 (m, 3H), 6.69 (d, J = 8.4 Hz, 2H), 5.16 (s, 1H), 5.09 (s, 1H), 4.64 (d, J = 7.7 Hz, 2H), 4.57 (d, J = 9.5 Hz, 1H), 4.44 (t, J = 8.2 Hz, 1H), 4.38 – 4.31 (m, 2H), 4.29 – 4.22 (m, 1H), 4.00 – 3.91 (m, 2H), 3.85 (s, 2H), 3.70 – 3.57 (m, 4H), 3.57 – 3.54 (m, 2H), 3.46 – 3.42 (m, 2H), 3.26 (p, J = 5.8 Hz, 2H), 2.92 (s, 6H), 2.46 – 2.42 (m, 3H), 2.10 – 2.02 (m, 1H), 1.93 – 1.87 (m, 1H), 1.55 (h, J = 7.3 Hz, 2H), 0.93 – 0.86 (m, 12H)
¹³C NMR (151 MHz, DMSO-d₆) δ 171.7, 171.6, 169.2, 168.6, 168.1, 165.3, 158.3 (q, J = 37.7 Hz), 155.7, 151.5, 151.0, 147.6, 141.8, 139.4, 136.6, 129.7, 128.9, 128.7, 128.6, 128.4, 128.2, 128.1, 127.7, 127.6, 127.4, 127.0, 115.2 (q, J = 289.5 Hz), 111.2, 70.4, 69.8, 69.6, 69.4, 69.1, 68.8, 66.9, 66.5, 58.7, 56.5, 55.7, 51.6, 50.9, 41.7, 38.6, 36.1, 35.7, 26.1, 20.7, 20.3, 15.8, 11.1
LC-MS (ESI) m/z: [M+H]⁺ calcd for C₅₈H₇₃N₉O₁₁S: 1104.6, found: 1104.5
Main, pp. 39–40
Benzyl 2-(4-{(S)-2-[4-(dimethylamino)benzoyl]-18-((2S,4R)-4-hydroxy-2-{[4-(4-methylthiazol-5-yl)benzyl]carbamoyl}pyrrolidine-1-carbonyl)-19,19-dimethyl-4,16-dioxo-8,11,14-trioxa-2,5,17-triazaicosyl}benzoyl)-1-propylhydrazine-1-carboxylate trifluoroacetate
Identifier Cbz-1c
¹H NMR (600 MHz, DMSO-d₆) δ 10.73 – 10.63 (m, 1H), 9.01 – 8.96 (m, 1H), 8.57 (t, J = 6.1 Hz, 1H), 8.00 (s, 1H), 7.83 (d, J = 8.5 Hz, 2H), 7.42 – 7.37 (m, 7H), 7.34 (s, 5H), 7.30 (d, J = 4.6 Hz, 2H), 7.28 – 7.24 (m, 1H), 6.70 (d, J = 8.3 Hz, 2H), 5.16 (s, 1H), 5.09 (s, 1H), 4.67 – 4.61 (m, 2H), 4.56 (d, J = 9.6 Hz, 1H), 4.44 (t, J = 8.2 Hz, 1H), 4.41 – 4.34 (m, 2H), 4.29 – 4.23 (m, 1H), 3.95 (s, 2H), 3.84 (s, 2H), 3.69 – 3.64 (m, 2H), 3.63 – 3.57 (m, 3H), 3.55 (ddd, J = 9.0, 5.0, 2.6 Hz, 3H), 3.53 – 3.50 (m, 2H), 3.47 (t, J = 6.4 Hz, 1H), 3.40 (t, J = 5.8 Hz, 2H), 3.23 (q, J = 5.7 Hz, 2H), 2.93 (s, 6H), 2.45 – 2.43 (m, 3H), 2.09 – 2.02 (m, 1H), 1.94 – 1.87 (m, 1H), 1.54 (p, J = 7.3 Hz, 2H), 0.96 – 0.85 (m, 12H)
¹³C NMR (151 MHz, DMSO-d₆) δ 171.7, 171.6, 171.3, 169.5, 169.1, 168.6, 168.5, 168.1, 167.8, 165.3, 158.3 (q, J = 37.8 Hz), 155.7, 151.5, 151.0, 147.6, 141.7, 139.5, 136.6, 131.2, 131.1, 129.6, 128.9, 128.7, 128.6, 128.4, 128.2, 128.1, 127.8, 127.7, 127.6, 127.5, 127.0, 115.2 (q, J = 289.4 Hz), 111.2, 70.4, 69.8, 69.6, 69.6, 69.0, 68.8, 66.5, 58.7, 56.5, 55.7, 50.9, 41.7, 38.6, 37.9, 35.7, 26.2, 20.3, 15.8, 11.1
LC-MS (ESI) m/z: [M+H]⁺ calcd for C₆₀H₇₇N₉O₁₂S: 1148.5, found: 1148.6
Main, pp. 40–41
Benzyl 2-(4-{(S)-2-[4-(dimethylamino)benzoyl]-21-((2S,4R)-4-hydroxy-2-{[4-(4-methylthiazol-5-yl)benzyl]carbamoyl}pyrrolidine-1-carbonyl)-22,22-dimethyl-4,19-dioxo-8,11,14,17-tetraoxa-2,5,20-triazatricosyl}benzoyl)-1-propylhydrazine-1-carboxylate trifluoroacetate
Identifier Cbz-1d
¹H NMR (600 MHz, DMSO-d₆) δ 10.73 – 10.60 (m, 1H), 8.99 (s, 1H), 8.57 (t, J = 6.1 Hz, 1H), 8.01 (s, 1H), 7.89 – 7.77 (m, 2H), 7.42 – 7.37 (m, 7H), 7.37 – 7.31 (m, 6H), 7.30 (d, J = 4.8 Hz, 2H), 7.26 (s, 1H), 6.70 (d, J = 8.3 Hz, 2H), 5.13 (d, J = 44.5 Hz, 2H), 4.68 – 4.61 (m, 2H), 4.56 (d, J = 9.5 Hz, 1H), 4.45 (t, J = 8.2 Hz, 1H), 4.42 – 4.33 (m, 2H), 4.29 – 4.22 (m, 1H), 3.96 (s, 2H), 3.84 (s, 2H), 3.70 – 3.63 (m, 1H), 3.63 – 3.61 (m, 1H), 3.62 – 3.56 (m, 3H), 3.57 (s, 1H), 3.56 – 3.52 (m, 2H), 3.54 – 3.50 (m, 2H), 3.51 – 3.45 (m, 4H), 3.40 (t, J = 5.9 Hz, 2H), 3.23 (q, J = 5.7 Hz, 2H), 2.93 (s, 6H), 2.44 (s, 3H), 2.08 – 2.03 (m, 1H), 1.93 – 1.88 (m, 1H), 1.55 (h, J = 7.3 Hz, 2H), 0.98 – 0.85 (m, 12H)
¹³C NMR (151 MHz, DMSO-d₆) δ 171.7, 171.6, 171.3, 169.5, 169.1, 168.6, 168.5, 168.1, 167.8, 165.3, 158.3 (q, J = 37.7 Hz), 155.7, 151.5, 151.1, 147.6, 141.7, 139.5, 136.6, 131.2, 129.6, 128.9, 128.7, 128.6, 128.4, 128.2, 127.9, 127.8, 127.7, 127.6, 127.5, 127.0, 115.3 (q, J = 289.6 Hz), 111.2, 70.4, 69.8, 69.8, 69.7, 69.6, 69.5, 69.0, 68.8, 66.9, 66.5, 58.7, 56.5, 55.7, 50.9, 41.7, 38.6, 37.9, 36.1, 35.7, 26.2, 20.7, 20.3, 15.8, 11.1
LC-MS (ESI) m/z: [M+H]⁺ calcd for C₆₂H₈₁N₉O₁₃S: 1193.4, found: 1193.1
Main, pp. 41–42
Benzyl 2-(4-{[4-(dimethylamino)-N-(2-{[(1-{(S)-17-[(2S,4R)-4-hydroxy-2-{[4-(4-methylthiazol-5-yl)benzyl]carbamoyl}pyrrolidine-1-carbonyl]-18,18-dimethyl-15-oxo-3,6,9,12-tetraoxa-16-azanonadecyl}-1H-1,2,3-triazol-4-yl)methyl]amino}-2-oxoethyl)benzamido]methyl}benzoyl)-1-propylhydrazine-1-carboxylate trifluoroacetate
Identifier Cbz-1e
¹H NMR (600 MHz, DMSO-d₆) δ 10.68 (m, 1H), 9.00 (s, 1H), 8.54 (t, J = 6.1 Hz, 1H), 8.46 (s, 1H), 7.90 – 7.89 (m, 1H), 7.88 (s, 1H), 7.83 (d, J = 8.3 Hz, 2H), 7.45 – 7.36 (m, 7H), 7.36 – 7.24 (m, 6H), 6.69 (d, J = 8.4 Hz, 2H), 5.16 (s, 1H), 5.09 (s, 1H), 4.67 (s, 2H), 4.55 (d, J = 9.4 Hz, 1H), 4.50 (t, J = 5.3 Hz, 2H), 4.46 – 4.40 (m, 2H), 4.34 (t, J = 5.2 Hz, 3H), 4.22 (m 1H), 3.87 (s, 2H), 3.80 (t, J = 5.3 Hz, 2H), 3.69 – 3.54 (m, 4H), 3.51 (dd, J = 5.9, 3.4 Hz, 2H), 3.48 – 3.43 (m, 10H), 2.93 (s, 6H), 2.54 (m, 1H), 2.44 (s, 3H), 2.39 – 2.32 (m, 1H), 2.10 – 1.99 (m, 1H), 1.96 – 1.86 (m, 1H), 1.55 (h, J = 7.3 Hz, 2H), 0.93 (s, 12H)
¹³C NMR (151 MHz, DMSO-d₆) δ 171.9, 171.6, 169.9, 169.5, 168.1, 165.3, 158.3 (q, J = 38.0 Hz), 155.7, 151.5, 151.0, 147.5, 141.7, 139.5, 136.6, 131.2, 131.1, 129.6, 128.8, 128.6, 128.6, 128.4, 128.2, 128.0, 127.7, 127.6, 127.4, 127.0, 123.2, 115.2 (d, J = 288.6 Hz), 111.3, 69.7, 69.7, 69.6, 69.5, 69.4, 68.9, 68.8, 66.9, 66.5, 62.5, 58.7, 56.3, 50.9, 49.3, 41.7, 37.9, 35.7, 35.3, 34.2, 26.3, 20.7, 20.3, 15.8, 13.8, 11.1
LC-MS (ESI) m/z: [M+H]⁺ calcd for C₆₆H₈₆N₁₂O₁₃S: 1287.6, found: 1287.6
Main, pp. 42–43
Benzyl 2-[4-({4-(dimethylamino)-N-[2-({[1-(6-{[(S)-1-((2S,4R)-4-hydroxy-2-{[4-(4-methylthiazol-5-yl)benzyl]carbamoyl}pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl]amino}-6-oxohexyl)-1H-1,2,3-triazol-4-yl]methyl}amino)-2-oxoethyl]benzamido}methyl)benzoyl]-1-propylhydrazine-1-carboxylate
Identifier Cbz-1f
¹H NMR (600 MHz, DMSO-d₆) δ 10.75 – 10.60 (m, 1H), 8.99 (s, 1H), 8.54 (t, J = 6.1 Hz, 1H), 8.45 (s, 1H), 7.90 (s, 1H), 7.84 (d, J = 9.2 Hz, 3H), 7.44 – 7.35 (m, 7H), 7.34 – 7.22 (m, 5H), 6.67 (d, J = 8.4 Hz, 2H), 5.16 (s, 1H), 5.09 (s, 1H), 4.67 (t, J = 7.2 Hz, 3H), 4.54 (d, J = 9.4 Hz, 1H), 4.46 – 4.40 (m, 2H), 4.37 – 4.27 (m, 5H), 4.25 – 4.19 (m, 1H), 3.87 (s, 2H), 3.70 – 3.63 (m, 2H), 3.53 – 3.42 (m, 2H), 2.93 (s, 6H), 2.44 (s, 3H), 2.27 – 2.20 (m, 1H), 2.15 – 2.09 (m, 1H), 2.06 – 2.00 (m, 1H), 1.94 – 1.88 (m, 1H), 1.79 (p, J = 7.3 Hz, 2H), 1.59 – 1.45 (m, 4H), 1.22 (p, J = 7.5 Hz, 2H), 0.97 – 0.85 (m, 12H)
¹³C NMR (151 MHz, DMSO-d₆) δ 171.9, 171.7, 169.7, 168.1, 165.3, 158.3 (q, J = 37.8 Hz), 155.7, 151.5, 151.0, 147.6, 141.8, 139.5, 136.6, 131.2, 129.6, 128.8, 128.6, 128.6, 128.4, 128.2, 128.0, 127.9, 127.8, 127.7, 127.6, 127.4, 127.0, 122.7, 115.3 (q, J = 289.6 Hz), 111.2, 68.9, 66.9, 66.5, 58.7, 56.3, 51.6, 50.9, 49.2, 42.3, 41.7, 37.9, 35.2, 34.6, 34.3, 29.5, 26.4, 26.4, 25.5, 24.8, 20.3, 15.9, 11.1
LC-MS (ESI) m/z: [M+H]⁺ calcd for C₆₁H₇₆N₁₂O₉S: 1153.6, found: 1153.6
Main, pp. 43–44
(2S,4R)-1-{(S)-12-(tert-butyl)-1-[4-(dimethylamino)phenyl]-1,4,10-trioxo-2-[4-(2-propylhydrazine-1-carbonyl)benzyl]-8-oxa-2,5,11-triazatridecan-13-oyl}-4-hydroxy-N-[4-(4-methylthiazol-5-yl)benzyl]pyrrolidine-2-carboxamide trifluoroacetate
Identifier 1a
¹H NMR (600 MHz, DMSO-d₆) δ 8.97 (s, 1H), 8.55 (t, J = 6.0 Hz, 1H), 7.77 (d, J = 8.1 Hz, 2H), 7.50 – 7.41 (m, 3H), 7.41 – 7.36 (m, 4H), 7.33 (d, J = 7.7 Hz, 2H), 6.68 (d, J = 8.4 Hz, 2H), 4.67 (s, 2H), 4.55 (d, J = 9.4 Hz, 1H), 4.44 (d, J = 8.2 Hz, 1H), 4.43 – 4.31 (m, 2H), 4.27 – 4.20 (m, 1H), 4.02 – 3.90 (m, 2H), 3.69 (d, J = 6.9 Hz, 2H), 3.67 – 3.64 (m, 1H), 3.60 (d, J = 10.8 Hz, 1H), 3.54 (t, J = 6.8 Hz, 2H), 3.52 – 3.47 (m, 2H), 3.34 – 3.25 (m, 2H), 2.92 (s, 6H), 2.85 – 2.78 (m, 2H), 2.61 (t, J = 6.8 Hz, 2H), 2.43 (s, 3H), 2.11 – 1.96 (m, 1H), 1.92 – 1.85 (m, 1H), 1.72 (p, J = 7.2 Hz, 2H), 0.92 – 0.87 (m, 12H)
¹³C NMR (151 MHz, DMSO-d₆) δ 171.7, 169.1, 168.5, 168.1, 158.1 (q, J = 36.5 Hz), 152.9, 152.2, 151.4, 151.2, 147.7, 141.4, 139.4, 131.1, 129.6, 128.8, 128.6, 128.6, 128.1, 127.4, 125.5, 122.3, 115.6 (d, J = 292.0 Hz), 111.0, 69.6, 69.4, 68.8, 60.9, 58.7, 56.5, 55.8, 46.9, 41.7, 38.5, 38.1, 37.9, 35.6, 33.9, 30.9, 26.2, 21.0, 15.9, 10.7
HPLC tR = 11.80 min (97.8 % purity)
HR-MS (ESI) m/z: [M+H]⁺ calcd for C₄₈H₆₃N₉O₈S: 926.4599, found: 926.4596
Main, p. 44
(2S,4R)-1-{(S)-15-(tert-butyl)-1-[4-(dimethylamino)phenyl]-1,4,13-trioxo-2-[4-(2-propylhydrazine-1-carbonyl)benzyl]-8,11-dioxa-2,5,14-triazahexadecan-16-oyl}-4-hydroxy-N-[4-(4-methylthiazol-5-yl)benzyl]pyrrolidine-2-carboxamide trifluoroacetate
Identifier 1b
¹H NMR (600 MHz, DMSO-d₆) δ 8.97 (s, 1H), 8.53 (t, J = 6.1 Hz, 1H), 7.77 (d, J = 8.0 Hz, 2H), 7.48 – 7.29 (m, 10H), 6.68 (d, J = 8.4 Hz, 2H), 4.65 (s, 3H), 4.56 (d, J = 9.5 Hz, 1H), 4.45 – 4.36 (m, 1H), 4.37 – 4.27 (m, 2H), 4.28 – 4.20 (m, 1H), 3.96 (d, J = 2.6 Hz, 2H), 3.87 (s, 2H), 3.72 – 3.64 (m, 3H), 3.63 – 3.51 (m, 6H), 3.47 – 3.42 (m, 2H), 3.31 – 3.21 (m, 2H), 2.92 (s, 6H), 2.43 (s, 3H), 2.09 – 2.02 (m, 1H), 1.94 – 1.86 (m, 1H), 1.73 (h, J = 7.2 Hz, 2H), 0.98 – 0.86 (m, 12H)
¹³C NMR (151 MHz, DMSO-d₆) δ 171.6, 171.6, 169.2, 168.6, 158.2 (q, J = 37.2 Hz), 152.9, 152.2, 151.4, 151.1, 147.7, 141.4, 139.4, 131.1, 129.7, 128.8, 128.6, 128.1, 127.4, 125.5, 122.4, 115.4 (q, J = 290.3 Hz), 111.1, 70.4, 69.5, 69.4, 69.1, 68.8, 58.7, 56.5, 55.7, 46.9, 41.6, 38.6, 38.1, 37.9, 36.1, 35.7, 33.9, 30.9, 26.1, 21.0, 15.9, 10.7
HPLC tR = 12.01 min (99.7 % purity)
HR-MS (ESI) m/z: [M+H]⁺ calcd for C₅₀H₆₇N₉O₉S: 970.4861, found: 970.4855
Main, pp. 44–45
(2S,4R)-1-{(S)-18-(tert-butyl)-1-[4-(dimethylamino)phenyl]-1,4,16-trioxo-2-[4-(2-propylhydrazine-1-carbonyl)benzyl]-8,11,14-trioxa-2,5,17-triazanonadecan-19-oyl}-4-hydroxy-N-[4-(4-methylthiazol-5-yl)benzyl]pyrrolidine-2-carboxamide trifluoroacetate
Identifier 1c
¹H NMR (600 MHz, DMSO-d₆) δ 8.97 (s, 1H), 8.56 (t, J = 6.0 Hz, 1H), 7.78 (d, J = 8.0 Hz, 2H), 7.48 – 7.42 (m, 2H), 7.39 (s, 5H), 7.35 – 7.31 (m, 2H), 6.68 (d, J = 8.4 Hz, 2H), 4.65 (s, 2H), 4.55 (d, J = 9.5 Hz, 1H), 4.44 (t, J = 8.1 Hz, 1H), 4.41 – 4.32 (m, 2H), 4.30 – 4.22 (m, 1H), 3.95 (s, 2H), 3.85 (s, 2H), 3.75 – 3.63 (m, 3H), 3.60 – 3.48 (m, 10H), 3.39 (t, J = 5.9 Hz, 2H), 3.22 (q, J = 5.7 Hz, 2H), 2.92 (s, 6H), 2.86 – 2.78 (m, 1H), 2.61 (t, J = 6.8 Hz, 1H), 2.43 (s, 3H), 2.10 – 1.96 (m, 2H), 1.93 – 1.86 (m, 1H), 1.73 (h, J = 7.2 Hz, 2H), 0.95 – 0.88 (m, 12H)
¹³C NMR (151 MHz, DMSO-d₆) δ 171.7, 169.1, 168.5, 158.0 (d, J = 35.4 Hz), 152.9, 152.2, 151.4, 151.2, 147.7, 141.4, 139.4, 131.1, 129.6 (d, J = 8.2 Hz), 128.8, 128.6, 128.1, 127.4, 125.5, 122.4, 111.0, 70.4, 69.8, 69.6, 69.6, 69.0, 68.8, 60.9, 58.7, 56.5, 55.7, 46.9, 41.7, 38.6, 38.1, 37.9, 36.1, 35.7, 35.1, 33.9, 30.9, 26.1, 25.1, 22.0, 21.0, 15.9, 13.9, 10.7
HPLC tR = 12.01 min (95.0 % purity)
HR-MS (ESI) m/z: [M+H]⁺ calcd for C₅₂H₇₁N₉O₁₀S: 1014.5123, found: 1014.5119
Main, pp. 45–46
(2S,4R)-1-{(S)-21-(tert-butyl)-1-[4-(dimethylamino)phenyl]-1,4,19-trioxo-2-[4-(2-propylhydrazine-1-carbonyl)benzyl]-8,11,14,17-tetraoxa-2,5,20-triazadocosan-22-oyl}-4-hydroxy-N-[4-(4-methylthiazol-5-yl)benzyl]pyrrolidine-2-carboxamide trifluoroacetate
Identifier 1d
¹H NMR (600 MHz, DMSO-d₆) δ 8.97 (s, 1H), 8.56 (t, J = 6.1 Hz, 1H), 7.78 (d, J = 8.1 Hz, 2H), 7.47 – 7.42 (m, 2H), 7.42 – 7.36 (m, 5H), 7.36 – 7.29 (m, 2H), 6.68 (d, J = 8.4 Hz, 2H), 4.68 – 4.62 (m, 2H), 4.56 (d, J = 9.6 Hz, 1H), 4.44 (t, J = 8.2 Hz, 1H), 4.40 (d, J = 6.4 Hz, 0H), 4.39 – 4.33 (m, 2H), 4.27 – 4.22 (m, 1H), 3.95 (s, 2H), 3.85 (s, 2H), 3.71 – 3.65 (m, 3H), 3.63 – 3.58 (m, 3H), 3.58 – 3.48 (m, 7H), 3.48 (s, 3H), 3.39 (d, J = 5.8 Hz, 4H), 3.23 (q, J = 5.7 Hz, 2H), 2.92 (s, 6H), 2.83 – 2.79 (m, 1H), 2.61 (t, J = 6.8 Hz, 1H), 2.43 (s, 3H), 2.08 – 2.02 (m, 1H), 1.93 – 1.86 (m, 1H), 1.73 (h, J = 7.2 Hz, 2H), 0.95 – 0.88 (m, 12H)
¹³C NMR (151 MHz, DMSO-d₆) δ 171.7, 169.5, 169.1, 168.6, 168.1, 167.8, 158.1 (d, J = 35.3 Hz), 152.9, 152.2, 151.4, 151.2, 147.7, 141.4, 139.4, 131.1, 129.7, 128.9, 128.7, 128.6, 128.1, 127.4, 125.5, 122.4, 121.9, 111.0, 70.4, 69.8, 69.8, 69.7, 69.6, 69.5, 69.0, 68.9, 67.0, 60.9, 58.7, 56.5, 55.7, 47.0, 41.7, 38.6, 38.1, 37.9, 36.1, 35.7, 33.9, 30.9, 26.2, 21.0, 15.9, 10.7
HPLC tR = 11.79 min (96.9 % purity)
HR-MS (ESI) m/z: [M+H]⁺ calcd for C₅₄H₇₅N₉O₁₁S: 1058.5385, found: 1058.5370
Main, p. 46
(2S,4R)-1-((S)-17-(tert-butyl)-1-{4-[(2-{4-(dimethylamino)-N-[4-(2-propylhydrazine-1-carbonyl)benzyl]benzamido}acetamido)methyl]-1H-1,2,3-triazol-1-yl}-15-oxo-3,6,9,12-tetraoxa-16-azaoctadecan-18-oyl)-4-hydroxy-N-[4-(4-methylthiazol-5-yl)benzyl]pyrrolidine-2-carboxamide
Identifier 1e
¹H NMR (600 MHz, DMSO-d₆) δ 8.97 (s, 1H), 8.54 (t, J = 6.1 Hz, 1H), 7.90 – 7.85 (m, 2H), 7.78 (d, J = 7.9 Hz, 2H), 7.45 (d, J = 8.0 Hz, 2H), 7.41 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H), 6.69 – 6.61 (m, 2H), 5.11 (d, J = 3.6 Hz, 1H), 4.68 (s, 2H), 4.54 (d, J = 9.4 Hz, 1H), 4.50 (t, J = 5.2 Hz, 2H), 4.45 – 4.38 (m, 2H), 4.33 (d, J = 5.7 Hz, 2H), 4.25 – 4.18 (m, 1H), 3.88 (s, 2H), 3.80 (t, J = 5.3 Hz, 2H), 3.70 (t, J = 6.9 Hz, 2H), 3.68 – 3.64 (m, 1H), 3.63 – 3.53 (m, 3H), 3.50 (dd, J = 5.9, 3.4 Hz, 2H), 3.48 – 3.42 (m, 10H), 3.30 (s, 4H), 2.92 (s, 6H), 2.55 – 2.53 (m, 1H), 2.44 (s, 3H), 2.37 – 2.30 (m, 1H), 2.05 – 1.99 (m, 1H), 1.93 – 1.88 (m, 1H), 1.73 (h, J = 7.2 Hz, 2H), 0.94 – 0.89 (m, 12H)
¹³C NMR (151 MHz, DMSO-d₆) δ 171.9, 171.7, 169.9, 169.5, 168.1, 152.9, 152.2, 151.4, 151.3, 147.7, 141.5, 139.5, 131.1, 129.6, 128.6, 127.4, 123.2, 111.0, 69.7, 69.7, 69.7, 69.6, 69.5, 69.4, 68.8, 68.8, 66.9, 58.7, 56.3, 56.3, 49.3, 47.0, 41.6, 37.9, 35.6, 35.3, 34.2, 26.3, 21.0, 15.9, 10.7
HPLC tR = 11.58 min (> 99.9 % purity)
HR-MS (ESI) m/z: [M+H]⁺ calcd for C₅₈H₈₀N₁₂O₁₁S: 1153.5868, found: 1153.5866
Main, pp. 46–47
(2S,4R)-1-[(S)-2-(6-{4-[(2-{4-(dimethylamino)-N-[4-(2-propylhydrazine-1-carbonyl)benzyl]benzamido}acetamido)methyl]-1H-1,2,3-triazol-1-yl}hexanamido)-3,3-dimethylbutanoyl]-4-hydroxy-N-[4-(4-methylthiazol-5-yl)benzyl]pyrrolidine-2-carboxamide
Identifier 1f
¹H NMR (600 MHz, DMSO-d₆) δ 8.97 (s, 1H), 8.53 (t, J = 6.1 Hz, 1H), 7.90 (s, 1H), 7.83 (d, J = 9.4 Hz, 1H), 7.78 (d, J = 7.9 Hz, 2H), 7.45 (d, J = 8.0 Hz, 2H), 7.41 (d, J = 8.2 Hz, 2H), 7.38 (d, J = 8.3 Hz, 2H), 7.31 (d, J = 8.3 Hz, 2H), 6.69 – 6.59 (m, 2H), 5.11 (d, J = 3.6 Hz, 1H), 4.68 (s, 2H), 4.53 (d, J = 9.4 Hz, 1H), 4.46 – 4.39 (m, 2H), 4.32 (dt, J = 14.2, 8.4 Hz, 5H), 4.21 (dd, J = 15.8, 5.5 Hz, 1H), 3.91 – 3.85 (m, 2H), 3.70 (t, J = 6.9 Hz, 2H), 3.66 – 3.60 (m, 2H), 3.56 – 3.52 (m, 1H), 2.92 (s, 6H), 2.84 – 2.79 (m, 1H), 2.63 – 2.58 (m, 1H), 2.44 (s, 3H), 2.40 – 2.34 (m, 1H), 2.28 – 2.19 (m, 1H), 2.15 – 2.07 (m, 1H), 2.06 – 1.99 (m, 1H), 1.93 – 1.87 (m, 1H), 1.79 (p, J = 7.3 Hz, 2H), 1.73 (p, J = 7.2 Hz, 2H), 1.55 – 1.43 (m, 2H), 0.94 – 0.88 (m, 12H)
¹³C NMR (151 MHz, DMSO-d₆) δ 171.9, 171.7, 169.7, 168.1, 153.0, 152.2, 151.4, 151.3, 147.7, 141.5, 139.5, 131.1, 129.6, 128.6, 127.4, 125.6, 122.7, 110.9, 68.8, 60.9, 58.7, 56.3, 49.2, 47.0, 41.7, 38.1, 38.0, 35.2, 34.6, 33.9, 30.9, 29.5, 26.4, 25.5, 24.8, 21.0, 15.9, 10.7
HPLC tR = 11.80 min (96.2 % purity)
HR-MS (ESI) m/z: [M+H]⁺ calcd for C₅₃H₇₀N₁₂O₇S: 1019.5289, found: 1019.5292
Main, pp. 47–48
(2S,4R)-1-((S)-2-(6-(4-((3-((2-(benzylamino)-2-oxoethyl)(4-(2-propylhydrazine-1-carbonyl)benzyl)carbamoyl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide bis(2,2,2-trifluoroacetate)
Identifier 2a
¹H NMR (600 MHz, DMSO-d₆) δ 11.21 (s, 1H), 8.98 (s, 1H), 8.54 (t, J = 6.1 Hz, 1H), 8.43 (dt, J = 19.1, 6.0 Hz, 1H), 8.19 (d, J = 12.1 Hz, 1H), 7.91 – 7.81 (m, 3H), 7.53 – 7.06 (m, 14H), 7.01 (d, J = 7.5 Hz, 1H), 5.10 (d, J = 36.6 Hz, 2H), 4.72 (s, 1H), 4.62 (s, 1H), 4.54 (d, J = 9.4 Hz, 1H), 4.46 – 4.40 (m, 2H), 4.38 – 4.30 (m, 4H), 4.29 – 4.19 (m, 3H), 4.04 (s, 1H), 3.86 (s, 1H), 3.72 – 3.60 (m, 2H), 3.11 – 2.99 (m, 2H), 2.44 (s, 3H), 2.25 (dt, J = 14.7, 7.6 Hz, 1H), 2.12 (ddd, J = 14.3, 8.1, 6.4 Hz, 1H), 2.03 (ddd, J = 10.3, 7.3, 2.5 Hz, 1H), 1.91 (ddd, J = 12.9, 8.5, 4.6 Hz, 1H), 1.82 (p, J = 7.4 Hz, 2H), 1.62 (h, J = 7.7 Hz, 2H), 1.52 (dp, J = 14.2, 6.7 Hz, 2H), 1.22 (p, J = 7.4 Hz, 2H), 0.92 (s, 12H)
¹³C NMR (151 MHz, DMSO-d₆) δ 171.9, 171.1, 169.7, 167.8, 165.3, 157.9, 151.4, 147.7, 142.3, 141.7, 139.5, 138.9, 137.3, 131.2, 129.7, 129.6, 128.6, 128.3, 127.9, 127.9, 127.8, 127.4, 127.2, 126.8, 126.7, 124.4, 119.0, 115.9, 113.0, 68.9, 61.3, 58.7, 56.3, 53.2, 51.8, 51.3, 49.3, 49.0, 42.2, 41.6, 37.9, 35.2, 34.6, 29.4, 26.4, 25.5, 24.8, 18.4, 15.9, 11.0
HPLC tR = 11.06 min (97.3 % purity)
HR-MS (ESI) m/z: [M+H]⁺ calcd for C₅₈H₇₁N₁₁O₈S: 1082.5281, found: 1082.5281
Main, pp. 48–49
((2S,4R)-1-((S)-1-(4-((3-((2-(benzylamino)-2-oxoethyl)(4-(2-propylhydrazine-1-carbonyl)benzyl)carbamoyl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)-14-(tert-butyl)-12-oxo-3,6,9-trioxa-13-azapentadecan-15-oyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide bis(2,2,2-trifluoroacetate)
Identifier 2b
¹H NMR (600 MHz, DMSO-d₆) δ 11.25 (s, 1H), 8.98 (s, 1H), 8.54 (t, J = 6.1 Hz, 1H), 8.43 (dt, J = 18.4, 6.0 Hz, 1H), 8.17 (d, J = 12.4 Hz, 1H), 7.87 (q, J = 8.7 Hz, 3H), 7.53 – 7.06 (m, 14H), 7.01 (d, J = 7.5 Hz, 1H), 5.11 (d, J = 33.3 Hz, 2H), 4.72 (s, 1H), 4.62 (s, 1H), 4.56 – 4.50 (m, 3H), 4.45 – 4.40 (m, 2H), 4.37 – 4.31 (m, 2H), 4.29 – 4.19 (m, 3H), 4.01 (s, 1H), 3.86 (s, 1H), 3.81 (dt, J = 8.6, 5.0 Hz, 2H), 3.69 – 3.53 (m, 4H), 3.45 (s, 8H), 3.06 (p, J = 7.2 Hz, 2H), 2.52 (s, 1H), 2.44 (s, 3H), 2.34 (dt, J = 14.6, 6.1 Hz, 1H), 2.08 – 2.00 (m, 1H), 1.91 (ddd, J = 12.9, 8.5, 4.6 Hz, 1H), 1.62 (h, J = 7.5 Hz, 2H), 0.93 (s, 12H)
¹³C NMR (151 MHz, DMSO-d₆) δ 171.9, 171.1, 169.9, 169.5, 167.8, 165.3, 157.9, 142.3, 141.8, 139.5, 138.9, 137.3, 131.2, 130.1, 129.8, 129.7, 129.6, 128.6, 128.3, 128.0, 127.8, 127.4, 127.2, 126.9, 126.7, 124.9, 119.0, 115.9, 113.0, 69.7, 69.6, 69.5, 69.4, 68.9, 68.7, 66.9, 61.3, 58.7, 56.3, 53.2, 51.8, 51.3, 49.4, 49.0, 42.2, 41.6, 37.9, 35.7, 35.3, 26.3, 18.4, 15.9, 11.0
HPLC tR = 10.97 min (99.4 % purity)
HR-MS (ESI) m/z: [M+H]⁺ calcd for C₆₁H₇₇N₁₁O₁₁S: 1172.5597, found: 1172.5597
Main, pp. 49–50
(2S,4R)-1-((S)-2-(6-(4-((4-((2-(benzylamino)-2-oxoethyl)(4-(2-propylhydrazine-1-carbonyl)benzyl)carbamoyl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)hexanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide bis(2,2,2-trifluoroacetate)
Identifier 2c
¹H NMR (600 MHz, DMSO-d₆) δ 11.24 (s, 1H), 8.98 (s, 1H), 8.54 (t, J = 6.1 Hz, 1H), 8.45 (t, J = 6.0 Hz, 1H), 8.23 (s, 1H), 7.85 (dd, J = 15.0, 8.6 Hz, 3H), 7.52 – 7.36 (m, 8H), 7.35 – 7.16 (m, 5H), 7.08 – 7.03 (m, 2H), 5.16 (s, 2H), 4.69 (d, J = 8.5 Hz, 2H), 4.54 (d, J = 9.3 Hz, 1H), 4.46 – 4.40 (m, 2H), 4.38 – 4.26 (m, 6H), 4.22 (dd, J = 15.8, 5.5 Hz, 1H), 4.00 (s, 1H), 3.88 (s, 1H), 3.71 – 3.61 (m, 2H), 3.06 (s, 2H), 2.44 (s, 3H), 2.25 (dt, J = 14.7, 7.6 Hz, 1H), 2.13 (dt, J = 14.3, 7.3 Hz, 1H), 2.04 (ddd, J = 10.9, 7.9, 2.3 Hz, 1H), 1.91 (ddd, J = 13.0, 8.6, 4.6 Hz, 1H), 1.82 (p, J = 7.8 Hz, 2H), 1.62 (h, J = 7.5 Hz, 2H), 1.52 (qt, J = 13.7, 6.9 Hz, 2H), 1.22 (p, J = 7.7 Hz, 2H), 0.93 (d, J = 7.0 Hz, 12H)
¹³C NMR (151 MHz, DMSO-d₆) δ 172.6, 172.2, 171.9, 171.2, 169.7, 167.9, 165.3, 159.1, 151.4, 147.7, 142.3, 142.2, 139.5, 139.0, 131.2, 129.6, 128.8, 128.6, 128.3, 128.0, 127.9, 127.8, 127.4, 127.3, 126.9, 124.4, 114.4, 68.9, 61.2, 58.7, 56.3, 53.8, 51.8, 51.6, 49.3, 42.2, 41.6, 37.9, 35.2, 34.6, 29.4, 26.7, 26.4, 25.5, 24.8, 18.4, 15.9, 11.0
HPLC tR = 11.00 min (97.7 % purity)
HR-MS (ESI) m/z: [M+H]⁺ calcd for C₅₈H₇₁N₁₁O₈S: 1082.5281, found: 1082.5284
Main, p. 50
(2S,4R)-1-((S)-1-(4-((4-((2-(benzylamino)-2-oxoethyl)(4-(2-propylhydrazine-1-carbonyl)benzyl)carbamoyl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)-14-(tert-butyl)-12-oxo-3,6,9-trioxa-13-azapentadecan-15-oyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide bis(2,2,2-trifluoroacetate)
Identifier 2d
¹H NMR (600 MHz, DMSO-d₆) δ 11.32 (s, 1H), 8.98 (s, 1H), 8.55 (t, J = 6.1 Hz, 1H), 8.45 (t, J = 6.0 Hz, 1H), 8.21 (s, 1H), 7.88 (t, J = 9.5 Hz, 3H), 7.54 – 7.36 (m, 8H), 7.35 – 7.15 (m, 5H), 7.09 – 7.03 (m, 2H), 5.17 (s, 2H), 4.70 (s, 2H), 4.54 (t, J = 8.3 Hz, 3H), 4.46 – 4.40 (m, 2H), 4.37 – 4.26 (m, 3H), 4.22 (dd, J = 15.8, 5.4 Hz, 1H), 3.94 (d, J = 65.6 Hz, 2H), 3.82 (t, J = 5.4 Hz, 2H), 3.69 – 3.52 (m, 4H), 3.46 (s, 8H), 3.08 (t, J = 7.6 Hz, 2H), 2.51 (d, J = 9.6 Hz, 1H), 2.44 (s, 3H), 2.34 (dt, J = 14.6, 6.2 Hz, 1H), 2.04 (dddd, J = 12.2, 7.7, 3.4, 1.5 Hz, 1H), 1.90 (ddd, J = 12.9, 8.5, 4.7 Hz, 1H), 1.63 (h, J = 7.5 Hz, 2H), 0.93 (d, J = 6.5 Hz, 13H)
¹³C NMR (151 MHz, DMSO-d₆) δ 171.9, 171.2, 169.9, 169.5, 167.9, 165.3, 159.1, 151.4, 147.7, 142.4, 142.2, 139.5, 139.0, 131.2, 129.9, 129.6, 128.8, 128.6, 128.3, 128.0, 127.9, 127.8, 127.4, 127.3, 126.9, 125.0, 114.4, 69.7, 69.6, 69.5, 69.4, 68.8, 68.6, 66.9, 61.2, 58.7, 56.3, 53.6, 51.7, 49.4, 49.3, 48.4, 42.2, 41.6, 37.9, 35.7, 35.3, 26.3, 18.2, 15.9, 11.0
HPLC tR = 10.92 min (97.8 % purity)
HR-MS (ESI) m/z: [M+H]⁺ calcd for C₆₁H₇₇N₁₁O₁₁S: 1172.5597, found: 1172.5597
Main, pp. 50–51
1-Benzyl 2-(tert-butyl) 1-propylhydrazine-1,2-dicarboxylate
Identifier 4
Rf (cyclohexane/EA, 4:1, v/v) 0.48
Mp ~30 °C
¹H NMR (600 MHz, CDCl₃) δ 7.39 – 7.28 (m, 4H), 6.43 (m, 1H), 5.23 – 5.02 (m, 2H), 3.45 (m, 2H), 1.60 (q, J = 7.5 Hz, 2H), 1.43 (m, 9H), 0.89 (m, 3H)
¹³C NMR (151 MHz, CDCl₃) δ 156.2, 136.2, 128.6, 128.2, 128.0, 81.6, 68.0, 52.4, 51.9 28.3, 21.0, 20.7, 11.3
LR-MS (ESI) m/z: [M+H]⁺ calcd for C₁₆H₂₄N₂O₄: 309.2, found: 309.2
Main, pp. 51–52
Benzyl 2-(4-{[(tert-butoxycarbonyl)amino]methyl}benzoyl)-1-propylhydrazine-1-carboxylate
Identifier 6
Rf (cyclohexane/EA, 1:1, v/v) 0.55
¹H NMR (500 MHz, 90 °C, DMSO-d₆) δ 10.37 (s, 1H), 7.92 – 7.85 (m, 1H), 7.79 (d, J = 7.7 Hz, 2H), 7.42 – 7.24 (m, 6H), 5.12 (d, J = 3.2 Hz, 2H), 4.20 (t, J = 6.1 Hz, 2H), 3.49 (t, J = 7.1 Hz, 2H), 1.59 (q, J = 7.3 Hz, 2H), 1.41 (s, 9H), 0.99 – 0.86 (m, 2H)
¹³C NMR (126 MHz, 90 °C DMSO-d₆) δ 166.6, 165.2, 155.3, 150.5, 143.8, 136.3, 130.7, 127.8, 127.3, 127.0, 126.8, 126.5, 120.1, 77.6, 66.3, 51.1, 43.2, 27.9, 20.0, 10.6
LR-MS (ESI) m/z: [M+H]⁺ calcd for C₂₄H₃₁N₃O₅: 442.2, found: 442.2
Main, pp. 52–53
Benzyl 2-[4-({[2-(tert-butoxy)-2-oxoethyl]amino}methyl)benzoyl]-1-propylhydrazine-1-carboxylate
Identifier 7
Rf (cyclohexane/EA, 1:2, v/v) 0.36
¹H NMR (600 MHz, DMSO-d₆) δ 10.67 – 10.59 (m, 1H), 7.79 (d, J = 8.0 Hz, 2H), 7.47 – 7.36 (m, 3H), 7.29 (d, J = 4.2 Hz, 3H), 5.20 – 5.03 (m, 2H), 3.76 (s, 3H), 3.47 (s, 2H), 3.18 (s, 2H), 1.55 (h, J = 7.3 Hz, 2H), 1.41 (s, 9H), 0.95 – 0.86 (m, 3H)
¹³C NMR (151 MHz, DMSO-d₆) δ 171.3, 165.5, 155.7, 144.7, 136.6, 130.7, 128.2, 127.9, 127.6, 127.4, 127.0, 80.1, 66.5, 51.6, 50.8, 50.2, 27.8, 20.3, 11.1
LR-MS (ESI) m/z: [M+H]⁺ calcd for C₂₅H₃₃N₃O₅: 456.6, found: 456.6
Main, pp. 53–54
Benzyl 2-[4-({N-[2-(tert-butoxy)-2-oxoethyl]-4-(dimethylamino)benzamido}methyl)benzoyl]-1-propylhydrazine-1-carboxylate
Identifier 8
Rf (cyclohexane/EA, 1:1, v/v) 0.30
¹H NMR (600 MHz, DMSO-d₆) δ 10.75 – 10.61 (m, 1H), 7.85 (s, 2H), 7.48 – 7.37 (m, 3H), 7.36 – 7.23 (m, 5H), 6.67 (d, J = 8.3 Hz, 2H), 5.17 (s, 1H), 5.09 (s, 1H), 4.68 (s, 2H), 3.93 (s, 2H), 3.48 (s, 2H), 2.92 (s, 6H), 1.56 (h, J = 7.3 Hz, 2H), 1.39 (s, 9H), 0.96 – 0.81 (m, 3H)
¹³C NMR (151 MHz, DMSO-d₆) δ 171.7, 165.3, 155.7, 151.4, 141.7, 136.6, 131.1, 128.4, 128.2, 127.8, 127.6, 127.5, 127.0, 111.0, 80.7, 66.9, 66.5, 51.6, 50.8, 40.1, 27.6, 20.3, 11.1
LR-MS (ESI) m/z: [M+H]⁺ calcd for C₃₄H₄₂N₄O₆: 602.3, found: 602.3
Main, p. 54
N-(4-{2-[(Benzyloxy)carbonyl]-2-propylhydrazine-1-carbonyl}benzyl)-N-[4-(dimethylamino)benzoyl]glycine
Identifier 9
Rf (DCM/MeOH, 9:1, v/v) 0.45
¹H NMR (600 MHz, DMSO-d₆) δ 12.72 (s, 1H), 10.86 – 10.68 (m, 1H), 7.87 (s, 2H), 7.47 – 7.36 (m, 3H), 7.28 (dd, J = 16.8, 6.4 Hz, 5H), 6.67 (s, 2H), 5.18 – 5.06 (m, 2H), 4.69 (s, 2H), 3.95 (s, 2H), 3.47 (s, 2H), 2.92 (s, 6H), 1.55 (h, J = 7.3 Hz, 2H), 0.89 (t, J = 7.6 Hz, 3H)
¹³C NMR (151 MHz, DMSO-d₆) δ 171.7, 165.3, 155.7, 151.3, 141.7, 136.6, 131.1, 128.4, 128.2, 127.9, 127.6, 127.5, 127.0, 111.0, 66.8, 66.5, 50.9, 40.1, 20.7, 20.3, 11.1
LR-MS (ESI) m/z: [M-H]⁻ calcd for C₃₀H₃₄N₄O₆: 545.2, found: 545.1
Main, pp. 54–55
Benzyl 2-(4-{[4-(dimethylamino)-N-[2-oxo-2-(prop-2-yn-1-ylamino)ethyl]benzamido]methyl}benzoyl)-1-propylhydrazine-1-carboxylate
Identifier 10
Rf (cyclohexane/EA, 1:4, v/v) 0.34
¹H NMR (600 MHz, DMSO-d₆) δ 10.78 – 10.59 (m, 1H), 8.40 (s, 1H), 7.83 (d, J = 8.6 Hz, 2H), 7.40 (d, J = 8.0 Hz, 3H), 7.37 – 7.21 (m, 6H), 6.68 (d, J = 8.3 Hz, 2H), 5.23 – 5.07 (m, 2H), 4.66 (s, 2H), 3.90 (dd, J = 5.5, 2.5 Hz, 2H), 3.86 (s, 2H), 3.48 (s, 2H), 3.14 (s, 1H), 2.93 (s, 6H), 1.55 (h, J = 7.3 Hz, 2H), 0.90 (t, J = 7.6 Hz, 3H)
¹³C NMR (151 MHz, DMSO-d₆) δ 171.7, 167.9, 165.3, 155.7, 151.2, 141.7, 136.6, 131.1, 128.6, 128.4, 128.2, 127.8, 127.7, 127.5, 127.0, 111.0, 80.8, 73.2, 66.9, 66.5, 51.6, 50.9, 40.1, 27.9, 20.3, 11.1
LR-MS (ESI) m/z: [M+H]⁺ calcd for C₃₃H₃₇N₅O₅: 584.4, found: 584.3
Main, p. 55
tert-Butyl [2-(2-{[(S)-1-((2S,4R)-4-hydroxy-2-{[4-(4-methylthiazol-5-yl)benzyl]carbamoyl}pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl]amino}-2-oxoethoxy)ethyl]carbamate
Identifier 12a
Rf (DCM/MeOH, 9:1, v/v) 0.44
¹H NMR (600 MHz, DMSO-d₆) δ 8.98 (s, 1H), 8.57 (t, J = 6.1 Hz, 1H), 7.40 (s, 5H), 6.89 – 6.81 (m, 1H), 5.13 (d, J = 3.6 Hz, 1H), 4.56 (d, J = 9.6 Hz, 1H), 4.47 – 4.32 (m, 2H), 4.28 – 4.22 (m, 1H), 3.94 (d, J = 5.5 Hz, 1H), 3.71 – 3.64 (m, 1H), 3.65 – 3.59 (m, 1H), 3.51 (s, 4H), 3.47 (t, J = 5.8 Hz, 2H), 2.44 (s, 3H), 2.10 – 2.01 (m, 1H), 1.96 – 1.87 (m, 1H), 1.36 (s, 9H), 0.95 (s, 9H)
¹³C NMR (151 MHz, DMSO-d₆) δ 171.7, 169.1, 168.5, 155.6, 151.4, 147.7, 139.4, 131.1, 129.7, 128.7, 127.5, 77.6, 69.8, 69.3, 68.8, 58.7, 56.5, 41.7, 37.9, 35.6, 28.2, 26.2, 18.1, 16.7, 15.9
LR-MS (ESI) m/z: [M+H]⁺ calcd for C₃₁H₄₅N₅O₇S: 632.3, found: 632.3
Main, p. 56
tert-Butyl (2-{2-[2-({(S)-1-[(2S,4R)-4-hydroxy-2-{[4-(4-methylthiazol-5-yl)benzyl]carbamoyl}pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl}amino)-2-oxoethoxy]ethoxy}ethyl)carbamate
Identifier 12b
Rf (DCM/MeOH, 9:1, v/v) 0.50
¹H NMR (600 MHz, MeOH-d₄) δ 8.89 – 8.87 (m, 1H), 8.59 (s, 1H), 7.69 (d, J = 9.4 Hz, 1H), 7.49 – 7.39 (m, 4H), 6.66 (t, J = 6.0 Hz, 1H), 4.72 (d, J = 9.2 Hz, 1H), 4.61 – 4.49 (m, 2H), 4.38 – 4.33 (m, 1H), 4.07 – 4.02 (m, 1H), 3.89 – 3.79 (m, 1H), 3.74 – 3.69 (m, 2H), 3.64 – 3.62 (m, 6H), 3.59 – 3.49 (m, 2H), 3.28 – 3.18 (m, 2H), 2.49 – 2.47 (m, 3H), 2.26 – 2.18 (m, 1H), 2.18 – 2.07 (m, 1H), 1.46 – 1.39 (m, 9H), 1.06 – 1.01 (m, 9H)
¹³C NMR (151 MHz, MeOH-d₄) δ 174.3, 172.2, 171.7, 158.4, 152.9, 149.1, 140.2, 133.4, 131.6, 130.4, 129.0, 80.2, 72.4, 71.5, 71.3, 71.2, 71.0, 60.8, 58.1, 43.8, 41.3, 38.9, 37.2, 30.8, 28.8, 27.0, 15.8
LR-MS (ESI) m/z: [M+H]⁺ calcd for C₃₃H₄₉N₅O₈S: 676.3, found: 676.3
Main, pp. 56–57
tert-Butyl {(S)-13-[(2S,4R)-4-hydroxy-2-{[4-(4-methylthiazol-5-yl)benzyl]carbamoyl}-pyrrolidine-1-carbonyl]-14,14-dimethyl-11-oxo-3,6,9-trioxa-12-azapentadecyl}carbamate
Identifier 12c
Rf (DCM/MeOH, 9:1, v/v) 0.50
¹H NMR (500 MHz, DMSO-d₆) δ 8.98 (s, 1H), 8.57 (t, J = 6.0 Hz, 1H), 8.31 (s, 1H), 7.49 – 7.34 (m, 5H), 6.71 (s, 1H), 5.13 (d, J = 3.6 Hz, 1H), 4.56 (d, J = 9.6 Hz, 1H), 4.48 – 4.33 (m, 3H), 4.31 – 4.22 (m, 1H), 3.97 (s, 1H), 3.69 – 3.65 (m, 1H), 3.61 (td, J = 5.0, 4.6, 2.1 Hz, 2H), 3.59 – 3.52 (m, 3H), 3.51 (d, J = 1.8 Hz, 4H), 3.35 (t, J = 6.1 Hz, 2H), 3.04 (q, J = 6.1 Hz, 2H), 2.44 (s, 3H), 2.09 – 2.02 (m, 1H), 1.95 – 1.87 (m, 1H), 1.36 (s, 9H), 0.95 (s, 9H)
¹³C NMR (126 MHz, DMSO-d₆) δ 171.6, 169.1, 168.5, 155.5, 151.3, 147.7, 139.4, 131.0, 129.7, 128.6, 127.4, 79.1, 77.5, 70.4, 69.7, 69.6 (d, J = 4.3 Hz), 69.5, 69.1, 68.8, 58.7, 56.4, 55.6, 41.6, 37.8, 35.6, 28.1, 26.1, 15.8
LR-MS (ESI) m/z: [M+H]⁺ calcd for C₃₅H₅₃N₅O₉S: 720.4, found: 720.3
Main, p. 57
tert-Butyl {(S)-16-[(2S,4R)-4-hydroxy-2-{[4-(4-methylthiazol-5-yl)benzyl]carbamoyl}-pyrrolidine-1-carbonyl]-17,17-dimethyl-14-oxo-3,6,9,12-tetraoxa-15-azaoctadecyl}carbamate
Identifier 12d
Rf (DCM/MeOH, 9:1, v/v) 0.60
¹H NMR (500 MHz, DMSO-d₆) δ 8.97 (s, 1H), 8.56 (t, J = 5.9 Hz, 1H), 8.31 – 8.29 (m, 1H), 7.43 – 7.37 (m, 4H), 6.69 (s, 1H), 5.14 – 5.07 (m, 1H), 4.57 (d, J = 9.6 Hz, 1H), 4.49 – 4.33 (m, 3H), 4.29 – 4.21 (m, 1H), 3.97 (s, 1H), 3.71 – 3.64 (m, 1H), 3.64 – 3.43 (m, 14H), 3.36 (t, J = 6.2 Hz, 2H), 3.05 (q, J = 5.9 Hz, 2H), 2.44 (s, 3H), 2.11 – 2.00 (m, 1H), 1.96 – 1.87 (m, 1H), 1.37 (s, 9H), 0.95 (s, 9H)
¹³C NMR (126 MHz, DMSO-d₆) δ 171.5, 169.1, 168.5, 155.5, 151.3, 147.7, 139.4, 131.1, 129.7, 128.6, 127.4, 79.1, 77.5, 70.4, 69.8, 69.7, 69.7, 69.6, 69.5, 69.4, 69.1, 68.8, 58.7, 56.5, 55.6, 41.7, 37.8, 35.6, 28.2, 26.1, 15.8
LR-MS (ESI) m/z: [M+H]⁺ calcd for C₃₇H₅₇N₅O₁₀S: 764.4, found: 764.3
Main, pp. 57–58
(2S,4R)-1-[(S)-1-azido-17-(tert-butyl)-15-oxo-3,6,9,12-tetraoxa-16-azaoctadecan-18-oyl]-4-hydroxy-N-[4-(4-methylthiazol-5-yl)benzyl]pyrrolidine-2-carboxamide
Identifier 12e
Rf (DCM/MeOH, 94:6, v/v) 0.30
¹H NMR (600 MHz, DMSO-d₆) δ 8.98 (s, 1H), 8.54 (t, J = 6.1 Hz, 1H), 7.89 (d, J = 9.4 Hz, 1H), 7.42 (d, J = 8.2 Hz, 2H), 7.38 (d, J = 8.3 Hz, 2H), 5.11 (d, J = 3.6 Hz, 1H), 4.55 (d, J = 9.4 Hz, 1H), 4.46 – 4.40 (m, 2H), 4.37 – 4.32 (m, 1H), 4.25 – 4.19 (m, 1H), 3.69 – 3.66 (m, 1H), 3.63 (s, 1H), 3.62 – 3.57 (m, 3H), 3.58 – 3.54 (m, 2H), 3.54 – 3.52 (m, 1H), 3.52 – 3.47 (m, 8H), 3.48 – 3.45 (m, 1H), 3.38 (t, J = 4.9 Hz, 2H), 2.59 – 2.50 (m, 2H), 2.44 (s, 3H), 2.39 – 2.30 (m, 1H), 2.07 – 1.99 (m, 1H), 1.95 – 1.86 (m, 1H), 0.94 (s, 9H)
¹³C NMR (151 MHz, DMSO-d₆) δ 171.9, 169.9, 169.5, 151.4, 147.7, 139.5, 131.1, 129.6, 128.6, 127.4, 69.8, 69.8, 69.7, 69.7, 69.5, 69.2, 68.9, 66.9, 58.7, 56.3, 56.3, 50.0, 41.6, 37.9, 35.7, 35.3, 26.3, 15.9
LR-MS (ESI) m/z: [M+H]⁺ calcd for C₃₃H₄₉N₇O₈S: 704.3, found: 704.3
Main, p. 58
(2S,4R)-1-[(S)-2-(6-azidohexanamido)-3,3-dimethylbutanoyl]-4-hydroxy-N-[4-(4-methylthiazol-5-yl)benzyl]pyrrolidine-2-carboxamide
Identifier 12f
Rf (DCM/MeOH, 9:1, v/v) 0.50
¹H NMR (600 MHz, CDCl₃) δ 8.73 (s, 1H), 7.37 – 7.31 (m, 4H), 6.22 (d, J = 8.8 Hz, 1H), 5.29 (s, 1H), 4.56 – 4.50 (m, 3H), 4.35 – 4.30 (m, 1H), 4.06 – 4.01 (m, 1H), 3.63 (s, 2H), 2.50 (s, 3H), 2.49 – 2.43 (m, 1H), 2.21 – 2.17 (m, 2H), 2.14 – 2.08 (m, 1H), 1.64 – 1.59 (m, 2H), 1.58 – 1.54 (m, 2H), 1.51 – 1.43 (m, 2H), 1.41 (d, J = 6.7 Hz, 1H), 1.39 – 1.32 (m, 2H), 0.93 (s, 9H)
¹³C NMR (151 MHz, CDCl₃) δ 173.5, 171.9, 171.0, 150.7, 148.1, 138.4, 132.0, 130.8, 129.6, 128.2, 70.1, 58.7, 57.6, 56.8, 53.6, 51.3, 43.3, 43.0, 36.3, 35.2, 28.6, 26.5, 25.1, 18.7, 17.4, 16.0
LR-MS (ESI) m/z: [M+H]⁺ calcd for C₂₈H₃₉N₇O₄S: 570.3, found: 570.3
Main, pp. 58–59
3-(prop-2-yn-1-yloxy)benzoic acid
Identifier 14m
¹H NMR (600 MHz, DMSO-d₆) δ 13.00 (s, 1H), 7.57 (dt, J = 7.8, 1.2 Hz, 1H), 7.52 (dd, J = 2.7, 1.4 Hz, 1H), 7.43 (t, J = 7.9 Hz, 1H), 7.23 (ddd, J = 8.2, 2.7, 1.0 Hz, 1H), 4.86 (d, J = 2.4 Hz, 2H), 3.58 (t, J = 2.3 Hz, 1H)
¹³C NMR (151 MHz, DMSO-d₆) δ 167.0, 157.2, 132.2, 129.7, 122.2, 119.8, 115.0, 79.0, 78.5, 55.6
LR-MS (ESI) m/z: [M-H]⁻ calcd for C₁₀H₈O₃: 175.0, found: 175.1
Main, p. 59
4-(prop-2-yn-1-yloxy)benzoic acid
Identifier 14p
¹H NMR (600 MHz, DMSO-d₆) δ 12.65 (s, 1H), 7.93 – 7.87 (m, 2H), 7.09 – 7.04 (m, 2H), 4.88 (d, J = 2.4 Hz, 2H), 3.60 (t, J = 2.4 Hz, 1H)
¹³C NMR (151 MHz, DMSO-d₆) δ 166.9, 160.7, 131.4, 131.2, 123.7, 114.6, 78.7, 78.6, 55.6
LR-MS (ESI) m/z: [M-H]⁻ calcd for C₁₀H₈O₃: 175.0, found: 175.1
Main, pp. 59–60
Methyl 4-((N-(2-(benzylamino)-2-oxoethyl)-3-(prop-2-yn-1-yloxy)benzamido)methyl)benzoate
Identifier 15m
¹H NMR (600 MHz, DMSO-d₆) δ 8.42 (dt, J = 28.0, 6.0 Hz, 1H), 7.95 (dd, J = 12.7, 7.8 Hz, 2H), 7.44 (dd, J = 54.2, 7.9 Hz, 2H), 7.38 – 7.29 (m, 3H), 7.29 – 7.14 (m, 3H), 7.11 – 6.99 (m, 3H), 4.83 – 4.60 (m, 4H), 4.30 (dd, J = 38.2, 5.8 Hz, 2H), 4.06 – 3.81 (m, 5H), 3.55 (dt, J = 31.8, 2.4 Hz, 1H)
¹³C NMR (151 MHz, DMSO-d₆) δ 171.0, 167.7, 166.0, 157.0, 142.8, 138.9, 137.2, 129.6, 129.4, 128.5, 128.3, 127.9, 127.2, 126.9, 119.4, 115.9, 113.2, 78.9, 78.4, 55.6, 52.1, 51.2, 48.9, 42.2
LR-MS (ESI) m/z: [M-H]⁻ calcd for C₂₈H₂₆N₂O₅: 469.2, found: 469.3
Main, pp. 60–61
Methyl 4-((N-(2-(benzylamino)-2-oxoethyl)-4-(prop-2-yn-1-yloxy)benzamido)methyl)benzoate
Identifier 15p
¹H NMR (600 MHz, DMSO-d₆) δ 8.45 (t, J = 6.0 Hz, 1H), 7.99 – 7.92 (m, 2H), 7.52 – 7.37 (m, 4H), 7.32 (t, J = 7.5 Hz, 2H), 7.29 – 7.16 (m, 3H), 7.03 – 6.95 (m, 2H), 4.88 – 4.60 (m, 4H), 4.36 – 4.23 (m, 2H), 3.85 (s, 5H), 3.59 (s, 1H)
¹³C NMR (151 MHz, DMSO-d₆) δ 171.1, 167.8, 166.0, 158.2, 142.9, 139.0, 129.5, 129.3, 128.6, 128.5, 128.3, 127.9, 127.2, 126.9, 114.5, 78.9, 78.5, 55.5, 52.1, 51.4, 49.1, 42.2
LR-MS (ESI) m/z: [M-H]⁻ calcd for C₂₈H₂₆N₂O₅: 469.2, found: 469.2
Main, p. 61
tert-butyl-2-(4-((N-(2-(benzylamino)-2-oxoethyl)-3-(prop-2-yn-1-yloxy)benzamido)methyl)benzoyl)-1-propylhydrazine-1-carboxylate
Identifier 17m
¹H NMR (600 MHz, DMSO-d₆) δ 10.50 (s, 1H), 8.42 (dt, J = 22.8, 6.1 Hz, 1H), 7.91 – 7.77 (m, 2H), 7.45 (d, J = 7.8 Hz, 1H), 7.34 (dt, J = 19.0, 7.7 Hz, 4H), 7.25 (q, J = 8.4, 7.4 Hz, 2H), 7.16 (d, J = 7.6 Hz, 1H), 7.06 (dd, J = 22.6, 6.4 Hz, 3H), 4.84 – 4.74 (m, 2H), 4.65 (d, J = 60.3 Hz, 2H), 4.30 (dd, J = 36.9, 5.8 Hz, 2H), 4.02 – 4.00 (m, 1H), 3.83 (s, 1H), 3.61 – 3.50 (m, 1H), 1.52 (s, 2H), 1.46 – 1.21 (m, 11H), 0.92 – 0.86 (m, 3H)
¹³C NMR (151 MHz, DMSO-d₆) δ 170.9, 167.7, 165.2, 157.0, 154.9, 141.0, 138.9, 137.2, 131.7, 129.6, 128.3, 127.7, 127.2, 126.8, 126.7, 119.4, 115.9, 113.2, 79.9, 79.4, 78.9, 78.4, 55.5, 50.1, 48.8, 42.2, 27.9, 20.4, 11.2
LR-MS (ESI) m/z: [M+H]⁺ calcd for C₃₅H₄₀N₄O₆: 613.3, found: 613.4
Main, pp. 61–62
tert-butyl-2-(4-((N-(2-(benzylamino)-2-oxoethyl)-4-(prop-2-yn-1-yloxy)benzamido)-methyl)benzoyl)-1-propylhydrazine-1-carboxylate
Identifier 17p
¹H NMR (600 MHz, DMSO-d₆) δ 10.50 (s, 1H), 8.44 (t, J = 6.0 Hz, 1H), 7.89 – 7.78 (m, 2H), 7.47 – 7.36 (m, 4H), 7.33 (t, J = 7.5 Hz, 2H), 7.29 – 7.16 (m, 3H), 7.00 (d, J = 8.2 Hz, 2H), 4.83 (s, 2H), 4.68 (s, 2H), 4.30 (d, J = 21.9 Hz, 2H), 3.93 (d, J = 81.3 Hz, 2H), 3.59 (d, J = 4.2 Hz, 1H), 1.56 – 1.48 (m, 2H), 1.47 – 1.23 (m, 11H), 0.93 – 0.85 (m, 3H)
¹³C NMR (151 MHz, DMSO-d₆) δ 171.1, 167.9, 165.3, 164.6, 158.2, 154.9, 154.3, 141.2, 139.0, 131.7, 128.6, 128.3, 127.7, 127.2, 126.9, 114.5, 79.7, 79.4, 78.9, 78.4, 63.2, 55.5, 50.1, 38.2, 27.8, 20.4, 11.2
LR-MS (ESI) m/z: [M+H]⁺ calcd for C₃₅H₄₀N₄O₆: 613.3, found: 614.0
Main, pp. 62–63
(2S,4R)-1-((S)-1-azido-14-(tert-butyl)-12-oxo-3,6,9-trioxa-13-azapentadecan-15-oyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide
Identifier 19
¹H NMR (500 MHz, DMSO-d₆) δ 8.98 (s, 1H), 8.53 (t, J = 6.1 Hz, 1H), 7.88 (d, J = 9.4 Hz, 1H), 7.44 – 7.36 (m, 4H), 5.11 (d, J = 3.6 Hz, 1H), 4.55 (d, J = 9.4 Hz, 1H), 4.48 – 4.39 (m, 2H), 4.35 (h, J = 4.2, 3.3 Hz, 1H), 4.22 (dd, J = 15.8, 5.5 Hz, 1H), 3.68 (dd, J = 10.6, 4.2 Hz, 1H), 3.64 – 3.57 (m, 5H), 3.56 – 3.46 (m, 8H), 3.38 (dd, J = 5.5, 4.4 Hz, 2H), 2.57 – 2.51 (m, 1H), 2.44 (s, 3H), 2.35 (dt, J = 14.6, 6.2 Hz, 1H), 2.09 – 1.99 (m, 1H), 1.91 (ddd, J = 12.9, 8.5, 4.6 Hz, 1H), 0.94 (s, 9H)
¹³C NMR (126 MHz, DMSO-d₆) δ 171.9, 169.9, 169.5, 151.4, 147.7, 139.5, 131.1, 129.6, 128.6, 127.4, 69.8, 69.7, 69.7, 69.4, 69.2, 68.8, 66.9, 56.3, 53.6, 50.0, 41.8, 37.9, 35.7, 35.3, 26.3, 16.7, 15.9
LR-MS (ESI) m/z: [M-H]⁻ calcd for C₃₁H₄₅N₇O₇S: 658.3, found: 658.5
Main, pp. 63–64
tert-butyl-2-(4-((N-(2-(benzylamino)-2-oxoethyl)-3-((1-(6-(((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)benzamido)methyl)benzoyl)-1-propylhydrazine-1-carboxylate
Identifier 20a
¹H NMR (600 MHz, DMSO-d₆) δ 10.49 (s, 1H), 8.98 (s, 1H), 8.53 (t, J = 6.1 Hz, 1H), 8.42 (q, J = 7.8, 5.8 Hz, 1H), 8.19 (d, J = 12.2 Hz, 1H), 7.90 – 7.78 (m, 3H), 7.47 – 7.20 (m, 11H), 7.17 – 7.08 (m, 3H), 7.02 (d, J = 7.3 Hz, 1H), 5.16 – 5.03 (m, 3H), 4.65 (d, J = 66.1 Hz, 2H), 4.53 (d, J = 9.4 Hz, 1H), 4.47 – 4.39 (m, 2H), 4.39 – 4.19 (m, 6H), 3.92 (d, J = 100.9 Hz, 2H), 3.71 – 3.60 (m, 2H), 2.44 (s, 3H), 2.25 (dt, J = 14.7, 7.5 Hz, 1H), 2.12 (dt, J = 14.4, 7.6 Hz, 1H), 2.07 – 2.00 (m, 1H), 1.90 (ddd, J = 12.9, 8.6, 4.6 Hz, 1H), 1.81 (q, J = 7.3 Hz, 2H), 1.52 (dq, J = 13.6, 6.6 Hz, 4H), 1.38 (d, J = 64.3 Hz, 9H), 1.28 – 1.15 (m, 4H), 0.92 (s, 12H)
¹³C NMR (151 MHz, DMSO-d₆) δ 171.9, 171.0, 169.7, 167.7, 167.5, 165.2, 157.9, 151.4, 147.7, 142.3, 141.1, 139.5, 139.2, 138.9, 137.3, 137.1, 131.2, 129.6, 128.8, 128.6, 128.3, 128.0, 127.7, 127.4, 127.2, 127.1, 126.9, 126.8, 126.7, 124.3, 119.1, 115.8, 113.0, 79.4, 68.8, 61.3, 58.7, 56.3, 51.4, 50.1, 49.3, 47.6, 45.7, 42.2, 41.6, 37.9, 35.2, 34.6, 29.4, 27.8, 26.4, 25.5, 24.8, 15.9, 11.2, 8.6
LR-MS (ESI) m/z: [M-H]⁻ calcd for C₆₃H₇₉N₁₁O₁₀S: 1180.6, found: 1181.3
Main, pp. 64–65
tert-butyl-2-(4-((N-(2-(benzylamino)-2-oxoethyl)-3-((1-((S)-14-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidine-1-carbonyl)-15,15-dimethyl-12-oxo-3,6,9-trioxa-13-azahexadecyl)-1H-1,2,3-triazol-4-yl)methoxy)benzamido)methyl)benzoyl)-1-propylhydrazine-1-carboxylate
Identifier 20b
¹H NMR (600 MHz, DMSO-d₆) δ 10.49 (s, 1H), 8.98 (s, 1H), 8.54 (t, J = 6.1 Hz, 1H), 8.41 (q, J = 6.7, 6.0 Hz, 1H), 8.17 (d, J = 12.2 Hz, 1H), 7.92 – 7.76 (m, 3H), 7.47 – 7.20 (m, 11H), 7.17 – 7.09 (m, 3H), 7.02 (d, J = 7.2 Hz, 1H), 5.17 – 5.07 (m, 3H), 4.65 (d, J = 64.9 Hz, 2H), 4.53 (td, J = 11.6, 10.6, 5.1 Hz, 3H), 4.46 – 4.39 (m, 2H), 4.37 – 4.28 (m, 2H), 4.27 – 4.19 (m, 2H), 4.04 – 3.78 (m, 4H), 3.70 – 3.54 (m, 4H), 3.53 – 3.42 (m, 8H), 3.38 (s, 2H), 2.54 (d, J = 7.1 Hz, 1H), 2.44 (s, 3H), 2.34 (dt, J = 14.6, 6.1 Hz, 1H), 2.03 (dq, J = 8.1, 4.5, 2.5 Hz, 1H), 1.90 (ddd, J = 12.9, 8.6, 4.6 Hz, 1H), 1.51 (s, 2H), 1.47 – 1.28 (m, 9H), 0.92 (s, 12H)
¹³C NMR (151 MHz, DMSO-d₆) δ 171.9, 171.0, 169.9, 169.5, 167.7, 165.6, 162.3, 157.9, 151.4, 147.7, 142.3, 141.3, 139.5, 139.2, 138.9, 137.3, 131.2, 129.7, 129.6, 128.8, 128.6, 128.3, 127.7, 127.4, 127.2, 127.1, 126.9, 126.8, 126.7, 124.9, 119.0, 115.8, 112.9, 79.4, 69.6, 69.6, 69.5, 69.4, 68.8, 68.6, 66.9, 61.2, 58.7, 56.3, 56.3, 49.4, 42.2, 42.1, 41.6, 37.9, 35.7, 35.6, 35.3, 30.7, 27.8, 26.3, 20.4, 15.9, 11.2
LR-MS (ESI) m/z: [M-H]⁻ calcd for C₆₆H₈₅N₁₁O₁₃S: 1270.6, found: 1271.3
Main, pp. 65–66
tert-butyl 2-(4-((N-(2-(benzylamino)-2-oxoethyl)-4-((1-(6-(((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)methoxy)benzamido)methyl)benzoyl)-1-propylhydrazine-1-carboxylate
Identifier 20c
¹H NMR (600 MHz, DMSO-d₆) δ 10.50 (s, 1H), 8.97 (s, 1H), 8.53 (t, J = 6.1 Hz, 1H), 8.44 (t, J = 5.9 Hz, 1H), 8.23 (s, 1H), 7.83 (dd, J = 17.5, 8.5 Hz, 3H), 7.46 – 7.36 (m, 8H), 7.32 (t, J = 7.5 Hz, 2H), 7.29 – 7.15 (m, 3H), 7.05 (d, J = 8.2 Hz, 2H), 5.20 – 5.09 (m, 3H), 4.68 (s, 2H), 4.58 – 4.51 (m, 1H), 4.48 – 4.40 (m, 2H), 4.39 – 4.27 (m, 5H), 4.22 (dd, J = 15.8, 5.5 Hz, 1H), 3.93 (d, J = 78.0 Hz, 2H), 3.70 – 3.60 (m, 2H), 2.44 (s, 3H), 2.25 (dt, J = 14.6, 7.5 Hz, 1H), 2.16 – 2.10 (m, 1H), 2.08 (s, 2H), 2.03 (dt, J = 10.2, 5.6 Hz, 1H), 1.90 (ddd, J = 12.9, 8.6, 4.6 Hz, 1H), 1.81 (d, J = 8.6 Hz, 2H), 1.52 (t, J = 11.9 Hz, 4H), 1.39 (d, J = 63.8 Hz, 9H), 1.26 – 1.19 (m, 2H), 0.92 (s, 12H)
¹³C NMR (151 MHz, DMSO-d₆) δ 171.9, 171.2, 169.7, 167.9, 165.3, 159.1, 154.9, 154.5, 151.4, 147.7, 142.2, 141.2, 139.5, 139.0, 131.2, 129.6, 128.8, 128.6, 128.3, 128.0, 127.7, 127.2, 126.9, 124.4, 114.4, 79.4, 68.9, 61.2, 58.7, 56.3, 55.8, 53.4, 51.6, 50.1, 49.3, 42.2, 41.6, 37.9, 35.2, 34.6, 30.7, 29.4, 27.8, 26.4, 25.5, 24.8, 15.9, 11.2
LR-MS (ESI) m/z: [M-H]⁻ calcd for C₆₃H₇₉N₁₁O₁₀S: 1180.6, found: 1180.7
Main, pp. 66–67
tert-butyl 2-(4-((N-(2-(benzylamino)-2-oxoethyl)-4-((1-((S)-14-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidine-1-carbonyl)-15,15-dimethyl-12-oxo-3,6,9-trioxa-13-azahexadecyl)-1H-1,2,3-triazol-4-yl)methoxy)benzamido)methyl)benzoyl)-1-propylhydrazine-1-carboxylate
Identifier 20d
¹H NMR (600 MHz, DMSO-d₆) δ 10.50 (s, 1H), 8.97 (s, 1H), 8.54 (t, J = 6.1 Hz, 1H), 8.44 (t, J = 5.9 Hz, 1H), 8.20 (s, 1H), 7.93 – 7.78 (m, 3H), 7.49 – 7.36 (m, 8H), 7.32 (t, J = 7.5 Hz, 2H), 7.29 – 7.15 (m, 3H), 7.06 (d, J = 8.2 Hz, 2H), 5.22 – 5.07 (m, 3H), 4.68 (s, 2H), 4.58 – 4.51 (m, 3H), 4.46 – 4.39 (m, 2H), 4.38 – 4.26 (m, 3H), 4.22 (dd, J = 15.8, 5.5 Hz, 1H), 3.93 (d, J = 76.5 Hz, 2H), 3.81 (s, 2H), 3.67 (dd, J = 10.6, 4.2 Hz, 1H), 3.64 – 3.54 (m, 3H), 3.48 (d, J = 31.0 Hz, 8H), 2.52 (d, J = 14.7 Hz, 2H), 2.44 (s, 3H), 2.34 (dt, J = 13.9, 6.2 Hz, 1H), 2.08 (d, J = 1.1 Hz, 1H), 2.03 (dd, J = 11.7, 8.6 Hz, 1H), 1.90 (ddd, J = 12.9, 8.6, 4.6 Hz, 1H), 1.51 (s, 2H), 1.39 (d, J = 64.0 Hz, 9H), 0.92 (s, 12H)
¹³C NMR (151 MHz, DMSO-d₆) δ 171.9, 171.2, 169.9, 169.5, 167.9, 165.3, 159.1, 154.9, 154.3, 151.4, 147.7, 142.2, 141.3, 139.5, 139.1, 139.0, 131.2, 129.6, 128.8, 128.6, 128.3, 128.0, 127.7, 127.4, 127.3, 126.9, 125.0, 114.3, 79.4, 69.7, 69.6, 69.5, 69.4, 68.8, 68.6, 66.9, 61.2, 58.7, 56.3, 56.3, 55.8, 51.6, 50.1, 49.4, 42.2, 41.6, 37.9, 35.6, 35.3, 30.7, 27.8, 26.3, 15.9, 11.2
LR-MS-(ESI) m/z: [M-H]⁻ calcd for C₆₆H₈₅N₁₁O₁₃S: 1270.6, found: 1270.7