Fmoc-(S)-Val photoprotected α-ketoacid with protected linker 39c (single diastereomer): was prepared following the general
procedure using Fmoc-(S)-Val photoprotected α-ketoacid 12c (1.00 equiv, 1.34 g, 2.33 mmol), allyl 5-(4-
chloromethyl)phenoxy)pentanoate (1.25 equiv, 821 mg, 2.91 mmol), K2CO3 (0.50 equiv, 162 mg, 1.17 mmol) and KI (0.25 equiv, 96.7 mg,
583 μmol) in dry acetone. The reaction mixture was stirred for 12 h at rt. The crude mixture was purified by flash chromatography (SiO2,
hexanes/AcOEt 17:3 to 7:3) to give the desired product (1.29 g, 1.57 mmol, 67 %) as white foam. 1H NMR (400 MHz, CDCl3) δ [ppm] = 7.81 –
7.72 (m, 3H, CH), 7.71 – 7.64 (m, 1H, CH), 7.64 – 7.52 (m, 3H, CH), 7.43 – 7.34 (m, 3H, CH), 7.34 – 7.25 (m, 4H, CH), 6.80 – 6.73 (m, 2H, CH),
5.91 (ddt, J = 17.3, 10.4, 5.7 Hz, 1H, CH), 5.58 (s, 1H, CH), 5.31 (ddd, J = 17.3, 3.1, 1.5 Hz, 1H, CH2), 5.27 – 5.18 (m, 2H, CH2), 5.13 (d, J = 11.7 Hz,
1H, CH2), 5.11 (d, J = 10.9 Hz, 1H, NH), 4.57 (d appt, J = 5.7, 1.4 Hz, 2H, CH2), 4.38 (dd, J = 10.4, 7.0 Hz, 1H, CH2), 4.28 (dd, J = 10.4, 7.4 Hz, 1H,
CH2), 4.22 (appt, J = 7.1 Hz, 1H, CH), 4.09 (dd, J = 10.9, 2.6 Hz, 1H, CH), 3.92 – 3.82 (m, 2H, CH2), 3.80 (d, J = 11.6 Hz, 1H, CH2), 3.58 (d,
J = 11.6 Hz, 1H, CH2), 2.43 – 2.34 (m, 2H, CH2), 2.31 (sep d, J = 6.8, 2.6 Hz, 1H, CH), 1.84 – 1.72 (m, 4H, CH2), 0.99 (d, J = 6.9 Hz, 3H, CH3),
0.97 (d, J = 6.8 Hz, 3H, CH3), 0.92 (s, 3H, CH3), 0.55 (s, 3H, CH3). 13C NMR (101 MHz, CDCl3) δ [ppm] = 173.2 (CO), 168.8 (CO), 159.3 (C), 156.7
(CO), 149.0 (C-NO2), 144.2* (C), 144.0* (C), 141.41* (C), 141.36* (CH), 132.4 (CH), 132.3 (CH), 131.2 (C), 130.9 (CH), 130.2 (CH), 128.7 (CH),
127.8* (CH), 127.7* (CH), 127.18* (CH, C), 127.15* (CH), 125.4* (CH), 125.3* (CH), 124.2 (CH), 120.0 (CH), 118.4 (CH2), 114.6 (CH), 102.2 (C),
76.4 (CH), 74.7 (CH2), 68.0 (CH2), 67.4 (CH2), 67.2 (CH2), 65.2 (CH2), 60.1 (CH), 47.3 (CH), 34.9 (C), 34.0 (CH2), 28.7 (CH2), 27.6 (CH2), 22.3
(CH3), 21.7 (CH2), 21.0 (CH3), 19.1 (CH3), 17.2 (CH3), (*Signals of rotamers). IR (υ/cm–1, thin film): 2960, 1735, 1528, 1514, 1472, 1351, 1301,
1219, 1173, 1087, 1059, 1013, 759, 740. HRMS (ESI): calculated for C47H53N2O11 [M+H]+: 821.3644, found: 821.3637.
Fmoc-(S)-Tyr photoprotected α-ketoacid with protected linker 39d (mixture of diastereomers): prepared following the general
procedure using Fmoc-(S)-Tyrosine photoprotected α-ketoacid 12d (1.00 equiv, 1.40 g, 2.02 mmol), allyl 5-(4-
chloromethyl)phenoxy)pentanoate (1.20 equiv, 684 mg, 2.40 mmol), K2CO3 (0.50 eq, 139 mg, 1.00 mmol) and KI (0.25 equiv, 84.0 mg,
0.50 mmol) in dry acetone. The reaction mixture was stirred for 12 h at rt. The crude mixture was purified by flash chromatography (SiO2,
hexanes/AcOEt 4/1 to 3/1) to give the desired product as white foam (872 mg, 0.93 mmol, 46%). The analytical data is given for an
inseparable mixture of diastereomers and rotamers. 1H NMR signals are generally described as multiplets. All observed diastereomeric 13
NMR signals are listed. 1H NMR (400 MHz, CDCl3) δ [ppm] = 7.85 – 7.68 (m, 3H), 7.69 – 7.53 (m, 2H), 7.49 (m, 2H), 7.44 – 7.21 (m, 7H), 7.09
(m, 2H), 6.89 – 6.72 (m, 4H), 5.98 – 5.85 (m, 1H), 5.75 (s, 0.5H), 5.59 (s, 0.5H), 5.31 (dt, J = 17.2, 1.4 Hz, 1H), 5.26 – 5.16 (m, 2H), 5.12 – 4.93
(m, 1H), 4.57 (m, 2H), 4.54-4.32 (m, 1H), 4.08 (m, 2H), 3.99-3.80 (m, 3H), 3.63 (t, J = 12.1 Hz, 1H), 3.22 (m, 1H), 2.71 (m, 1H), 2.38 (m, 2H),
1.90 – 1.68 (m, 4H), 1.21 (s, 9H), 0.94 (m, 3H), 0.59 (s, 3H). 13C NMR (101 MHz, CDCl3) δ [ppm] = 173.0, 168.4, 159.2, 159.1, 155.7, 155.6,
153.9, 148.9, 148.8, 144.1, 143.9, 143.88, 143.82, 141.2, 141.1, 132.2, 132.19, 132.16, 132.12, 131.2, 130.9, 130.8, 130.7, 130.4, 130.1, 129.9,
129.8, 129.7, 129.6, 128.7, 128.6, 127.7, 127.63, 127.60, 127.6, 127.5, 127.2, 127.1, 127.0, 127.01, 126.9, 125.3, 125.22, 125.20, 125.1, 124.1,
124.06, 124.03, 123.9, 119.9, 119.8, 118.2, 114.4, 101.2, 101.1, 78.2, 77.2, 76.0, 74.7, 74.6, 67.9, 67.8, 67.3, 67.2, 67.1, 67.0, 65.0, 57.4, 57.1,
47.0, 46.9, 34.9, 34.86, 34.81, 34.6, 33.8, 28.9, 28.8, 28.7, 28.6, 28.5, 21.6, 20.9, 20.8, 18.9. IR (υ/cm–1, thin film): 3356, 2972, 2874, 1737,
1611, 1529, 1449, 1242, 1173, 1065, 909, 737. HRMS (ESI): calculated for C55H60N2O12 [M+Na]+: 963.4038, found: 963.4031.
C
Fmoc-(S)-Gln photoprotected α-ketoacid with protected linker 39e (single diastereomer): was prepared following the general
procedure using Fmoc-(S)-Gln photoprotected α-ketoacid 12e (1.00 equiv, 120 mg, 0.14 mmol), allyl 5-(4-
chloromethyl)phenoxy)pentanoate (1.20 equiv, 48.0 mg, 0.17 mmol), K2CO3 (0.50 equiv, 10.0 mg, 0.07 mmol) and KI (0.25 equiv, 6.0 mg,
0.035 mmol) in dry acetone. The reaction mixture was stirred for 12 h at rt. The crude mixture was purified by flash chromatography (SiO2,
hexanes/AcOEt 4/1 to 3/1) to give the desired product as white foam (125 mg, 0.11 mmol, 81%). 1H NMR (400 MHz, CDCl3) δ [ppm] = 7.77
(m, 3H, CH), 7.62 (m, 1H, CH), 7.58 – 7.48 (m, 3H, CH), 7.43 – 7.34 (m, 3H, CH), 7.29 (m, 2H, CH), 7.23 – 7.07 (m, 17H), 6.57 (d, J = 8.7 Hz, 2H,
CH), 5.90 (m, 1H, CH), 5.51 (s, 1H, CH), 5.31 (m, 1H, CH2), 5.27 – 5.19 (m, 2H, CH2), 5.08 (d, J = 10.3 Hz, 1H, NH), 5.02 (d, J = 11.0 Hz, 1H,
CH2), 4.57 (m, 2H, CH2), 4.34 (m, 1H, CH2), 4.22 (m, 2H, CH2+CH), 4.12 (m, 1H, CH), 3.91 (d, J = 11.5 Hz, 1H, CH2), 3.78 – 3.61 (m, 2H, CH2),
3.56 (d, J = 11.5 Hz, 1H, CH2), 2.33 (m, 4H, CH2), 1.85 (m, 1H, CH2), 1.78 – 1.58 (m, 3H, CH2), 0.87 (s, 3H, CH3), 0.55 (s, 3H, CH3). 13C NMR (101
MHz, CDCl3) δ [ppm] = 173.2 (CO), 171.6 (CO), 168.5 (CO), 159.1 (CO), 156.7 (C), 148.9 (C), 144.9 (C), 144.2 (C), 143.7 (C), 141.5* (C), 141.4*
(C), 132.7 (C), 132.4 (C), 130.8 (C), 130.6 (CH), 130.5 (C), 128.9 (CH), 128.7 (CH), 127.9 (CH), 127.86* (CH), 127.81* (CH), 127.22* (CH),
127.18* (CH), 127.0 (CH), 126.9 (CH), 125.4* (CH), 125.3* (CH), 124.0 (CH), 120.1* (CH), 120.0* (CH), 118.7 (CH), 114.5 (CH), 100.9 (C), 76.7
(CH), 74.7 (CH2), 70.8 (C), 67.9 (CH2), 67.3 (CH2), 67.0 (CH2), 65.2 (CH2), 56.1 (CH), 47.3 (CH), 35.0 (CH2), 34.1 (C), 34.0 (CH2), 28.7 (CH2), 26.1
(CH2), 21.7 (CH2), 20.9 (CH3), 18.9 (CH3), (*Signals of rotamers). IR (υ/cm–1, thin film): 3338, 3058, 2946, 2874, 1735, 1528, 1246, 1174, 1058,
738, 701. HRMS (ESI): calculated for C66H65N3O12 [M+H]+: 1092.4641, found: 1092.4636.
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