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7.4 Hz, 2 H), 7.31–7.27 (t, J = 7.4 Hz, 2 H), 5.48–5.46 (d, J = 7.3 Hz,
1 H), 5.22 (s, 2 H), 4.65–4.57 (br. s, 1 H), 4.43–4.34 (m, 3 H), 4.22–
4.19 (t, J = 6.9 Hz, 1 H), 3.10–3.02 (m, 2 H), 1.88–1.84 (m, 1 H), 1.72–
9 H), 7.15–7.13 (m, 6 H), 6.75 (s, 1 H), 6.13–6.11 (d, J = 8.8 Hz, 1 H),
5.21–5.11 (q, J = 12.8 Hz, 2 H), 4.69–4.65 (m, 1 H), 4.43–4.38 (m, 1
H), 4.30–4.26 (t, J = 8.9 Hz, 1 H), 4.20–4.16 (t, J = 7.1 Hz, 1 H), 3.18–
1.68 (m, 1 H), 1.42 (s, 9 H), 1.38–1.24 (m, 4 H) ppm. 13C NMR 3.13 (dd, J1 = 4.2, J2 = 15.8 Hz, 1 H), 2.87–2.82 (dd, 1J = 4.2, 2J =
(100 MHz, CDCl3): δ = 172.4, 156.2, 143.9, 141.4, 139.5, 132.9, 132.6,
132.2, 131.8, 128.7, 128.0, 127.8, 127.2, 125.2, 120.1, 79.3, 67.2, 66.4,
54.0, 47.3, 40.0, 32.1, 29.8, 28.5, 22.5 ppm. 31P NMR (162 MHz,
CDCl3): δ = 29.37 ppm. HRMS (ESI): m/z calcd. for [C45H47N2O7P +
H]+: 759.3199; found: 759.3183.
15.8 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 171.0, 169.4,
156.4, 144.3, 144.0, 143.8, 141.4, 139.6, 132.6, 132.5, 132.2, 132.0,
128.7, 128.6, 128.2, 127.9, 127.6, 127.5, 127.4, 127.2, 125.3, 120.1,
71.1, 67.4, 66.6, 51.2, 47.2, 38.8 ppm. 31P NMR (162 MHz, CDCl3): δ =
29.38 ppm. HRMS (ESI): m/z calcd. for [C57H47N2O6P + H]+: 887.3250;
found: 887.3230.
1
Compound 5d: Yield 227 mg (99 %); white solid; m.p. 85–86 °C. H
1
NMR (400 MHz, CDCl3): δ = 7.76–7.74 (d, J = 7.5 Hz, 2 H), 7.66–7.52 Compound 5i: Yield 195 mg (99 %); white solid; m.p. 78–79 °C. H
(m, 10 H), 7.46–7.36 (m, 8 H), 7.29–7.26 (t, J = 7.2 Hz, 2 H), 5.86–
5.84 (d, J = 8.6 Hz, 1 H), 5.29–5.20 (dd, J = 12.8, 12.4 Hz, 2 H), 4.69–
4.66 (m, 1 H), 4.44–4.31 (m, 2 H), 4.24–4.21 (t, J = 7.0 Hz, 1 H), 3.01–
2.95 (dd, J = 4.3, 17.0 Hz, 1 H), 2.81–2.76 (dd, J = 4.2, 17.0 Hz, 1 H),
1.39 (s, 9 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 170.9, 170.2, 156.1,
NMR (400 MHz, CDCl3): δ = 7.76–7.75 (d, J = 7.6 Hz, 2 H), 7.70–7.63
(m, 6 H), 7.59–7.53 (m, 4 H), 7.48–7.37 (m, 8 H), 7.31–7.28 (t, J =
7.6 Hz, 2 H), 5.37–5.35 (d, J = 7.6 Hz, 1 H), 5.23 (s, 2 H), 4.49–4.38
(m, 3 H), 4.23–4.19 (t, J = 7.2 Hz, 1 H), 1.46–1.44 (d, J = 7.2 Hz, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 172.9, 155.8, 144.0, 143.8,
143.9, 143.8, 141.4, 139.5, 132.7, 132.6, 132.5, 132.2, 132.1, 131.7, 141.4, 139.5, 132.9, 132.6, 132.5, 132.2, 132.1, 131.9, 128.7, 128.6,
128.7, 128.6, 128.0, 127.9, 127.2, 125.2, 120.1, 82.1, 67.4, 66.7, 50.7,
127.9, 127.8, 127.2, 125.2, 120.1, 67.2, 66.4, 53.6, 49.8, 47.3, 31.7,
47.2, 37.8, 28.1 ppm. 31P NMR (162 MHz, CDCl3): δ = 29.75 ppm.
22.8, 18.7, 14.3 ppm. 31P NMR (162 MHz, CDCl3): δ = 29.28 ppm.
HRMS (ESI): m/z calcd. for [C42H40NO7P + H]+: 702.2621; found: HRMS (ESI): m/z calcd. for [C37H32NO5P + H]+: 602.2096; found:
702.2602.
602.2080.
1
1
Compound 5e: Yield 257 mg (97 %); white solid; m.p. 98–99 °C. H
Compound 5j: Yield 189 mg (99 %); white solid; m.p. 79–80 °C. H
NMR (400 MHz, CDCl3): δ = 8.10–8.08 (d, J = 7.7 Hz, 1 H), 7.76–7.74 NMR (400 MHz, CDCl3): δ = 7.76–7.75 (d, J = 7.5 Hz, 2 H), 7.70–7.63
(d, J = 7.5 Hz, 2 H), 7.68–7.61 (m, 6 H), 7.56–7.36 (m, 14 H), 7.31– (m, 6 H), 7.60–7.53 (m, 4 H), 7.48–7.42 (m, 6 H), 7.41–7.37 (t, J =
7.25 (m, 3 H), 7.21–7.18 (t, J = 7.5 Hz, 1 H), 5.48–5.46 (d, J = 8.2 Hz, 7.5 Hz, 2 H), 7.31–7.27 (t, J = 7.4 Hz, 2 H), 5.42–5.37 (m, 1 H), 5.23
1 H), 5.21–5.06 (dd, J = 12.9, 47.8 Hz, 2 H), 4.84–4.79 (m, 1 H), 4.41– (s, 2 H), 4.41–4.39 (d, J = 7.1 Hz, 2 H), 4.24–4.21 (t, J = 7.0 Hz, 1 H),
4.34 (m, 2 H), 4.22–4.18 (t, J = 7.0 Hz, 1 H), 3.28–3.27 (d, J = 5.7 Hz, 4.06–4.05 (d, J = 5.6 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
2 H), 1.63 (s, 9 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 171.6, 155.8,
169.9, 156.4, 143.9, 141.4, 139.3, 132.9, 132.6, 132.2, 132.1, 131.8,
149.6, 143.9, 143.8, 141.4, 139.1, 135.5, 132.9, 132.6, 132.5, 132.2, 128.7, 128.6, 128.1, 128.0, 127.9, 127.2, 125.2, 120.1, 67.4, 66.4, 47.2,
132.1, 131.8, 130.4, 128.7, 128.6, 127.8, 127.2, 125.2, 124.8, 124.3, 42.9 ppm. 31P NMR (162 MHz, CDCl3): δ = 29.33 ppm. HRMS (ESI):
122.8, 120.1, 118.9, 115.5, 114.8, 84.0, 67.4, 66.6, 54.3, 47.2,
28.2 ppm. 31P NMR (162 MHz, CDCl3): δ = 29.32 ppm. HRMS (ESI):
m/z calcd. for [C50H45N2O7P + H]+: 817.3043; found: 817.3031.
m/z calcd. for [C36H30NO5P + H]+: 588.1940; found: 588.1925.
Compound 5k: Yield 99 %; white solid; m.p. 99–100 °C. 1H NMR
(400 MHz, CDCl3): δ = 7.77–7.75 (d, J = 7.6 Hz, 2 H), 7.69–7.64 (m,
6 H), 7.56–7.53 (t, J = 7.4 Hz, 4 H), 7.48–7.44 (m, 4 H), 7.41–7.36 (m,
4 H), 7.31–7.27 (t, J = 7.4 Hz, 2 H), 6.95–6.93 (d, J = 8.4 Hz, 2 H),
6.87–6.85 (d, J = 8.4 Hz, 2 H), 5.28–5.26 (d, J = 7.9 Hz, 1 H), 5.22–
5.13 (q, J = 8.5 Hz, 2 H), 4.70–4.68 (m, 1 H), 4.44–4.32 (m, 2 H), 4.21–
Compound 5f: Yield 304 mg (99 %); white solid; m.p. 117–118 °C.
1H NMR (400 MHz, CDCl3): δ = 7.75–7.73 (d, J = 7.5 Hz, 2 H), 7.69–
7.63 (m, 4 H), 7.60–7.55 (m, 4 H), 7.53–7.46 (m, 8 H), 7.39–7.35 (t,
J = 7.4 Hz, 2 H), 7.29–7.27 (d, J = 7.4 Hz, 2 H), 6.61 (br. s, 2 H), 5.88
(br. s, 1 H), 5.50–5.35 (dd, J1 = 9.7, J2 = 52.8 Hz, 2 H), 5.03–5.00 (d, 4.18 (t, J = 6.9 Hz, 1 H), 3.09–3.06 (m, 2 H), 1.30 (s, 9 H) ppm. 13C
J = 11.8 Hz, 1 H), 4.36–4.34 (m, 3 H), 4.20–4.16 (t, J = 7.0 Hz, 1 H),
NMR (100 MHz, CDCl3): δ = 171.5, 155.7, 154.7, 143.9, 143.8, 141.4,
3.25–3.15 (m, 2 H), 2.90 (s, 2 H), 2.78–2.67 (m, 2 H), 2.58 (s, 3 H), 139.2, 132.9, 132.6, 132.5, 132.2, 132.1, 129.9, 128.8, 128.6, 128.2,
2.51 (s, 3 H), 2.06 (s, 3 H), 1.68–1.57 (m, 2 H), 1.42 (s, 6 H) ppm. 13C
128.0, 127.9, 127.2, 125.2, 124.3, 120.1, 78.6, 67.1, 66.5, 55.0, 47.3,
NMR (100 MHz, CDCl3): δ = 172.0, 158.6, 156.6, 156.2, 143.8, 141.3,
37.8, 28.9 ppm. 31P NMR (162 MHz, CDCl3): δ = 29.29 ppm. HRMS
140.0, 138.3, 133.3, 132.5, 132.4, 132.2, 132.0, 131.9, 131.8, 130.8, (ESI): m/z calcd. for [C47H44NO6P + H]+: 750.2984; found: 750.2966.
128.9, 128.8, 127.8, 127.2, 125.2, 124.6, 121.1, 120.0, 119.8, 117.4,
Synthesis of Compound 6a: Boc-Phe-OBndpp 5a (80 mg) was dis-
86.4, 68.0, 67.2, 66.2, 53.5, 47.1, 43.3, 40.5, 29.6, 28.6, 25.2, 19.4, 18.1,
solved in 60 % TFA/CH2Cl2 (5 mL) and stirred at room temperature.
12.6 ppm. 31P NMR (162 MHz, CDCl3): δ = 31.03 ppm. HRMS (ESI):
After 1 h, the solvent mixture was evacuated, and the crude mate-
m/z calcd. for [C53H55N4O8PS + H]+: 939.3556; found: 939.3538.
rial was dissolved in CH2Cl2. After washing twice with 1
the organic layer was dried with MgSO4, filtered, and concentrated
M HCl (aq),
1
Compound 5g: Yield 204 mg (99 %); white solid; m.p. 81–82 °C. H
NMR (400 MHz, CDCl3): δ = 7.77–7.75 (d, J = 7.2 Hz, 2 H), 7.70–7.53 to afford crude 6a HCl salt. GAP purification was conducted by
(m, 10 H), 7.48–7.44 (m, 6 H), 7.41–7.37 (t, J = 7.2 Hz, 2 H), 7.32–
7.28 (t, J = 7.2 Hz, 2 H), 5.36–5.34 (d, J = 8.8 Hz, 1 H), 5.22 (s, 2 H),
4.44–4.32 (m, 3 H), 4.24–4.21 (t, J = 6.8 Hz, 1 H), 2.26–2.17 (m, 1 H),
dissolving the crude material in a minimal amount of ethyl acetate,
followed by precipitation with petroleum ether. The purified prod-
uct was isolated by filtration, yield 71 mg (99 %); white solid; m.p.
0.97–0.95 (d, J = 6.8 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 68–71 °C (decomp.). 1H NMR (400 MHz, CDCl3): δ = 7.57–7.40 (m,
172.0, 156.3, 143.9, 143.8, 141.4, 139.4, 132.6, 132.5, 132.2, 132.1, 12 H), 7.10–7.04 (m, 7 H), 4.99–4.96 (d, J = 10.4 Hz, 2 H), 4.41 (br. s,
128.7, 128.6, 128.1, 128.0, 127.8, 127.1, 125.1, 120.1, 67.1, 66.2, 59.1,
1 H), 3.43 (br. s, 1 H), 3.25 (br. s, 1 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 169.1, 138.6, 134.3, 132.5, 132.3, 132.2, 132.1, 132.0,
47.2, 31.3, 19.1, 17.6 ppm. 31P NMR (162 MHz, CDCl3): δ =
29.45 ppm. HRMS (ESI): m/z calcd. for [C39H36NO5P + H]+: 630.2409; 131.5, 129.6, 128.8, 128.7, 128.6, 128.3, 128.2, 127.5, 67.0, 54.6,
found: 630.2392.
36.6 ppm. 31P NMR (162 MHz, CDCl3): δ = 29.79 ppm. HRMS (ESI):
m/z calcd. for [C28H26NO3P + H]+: 456.1729; found: 456.1725.
Compound 5h: Yield 287 mg (99 %); white solid; m.p. 121–122 °C.
1H NMR (400 MHz, CDCl3): δ = 7.76–7.71 (t, J = 6.4 Hz, 2 H), 7.65–
7.51 (m, 12 H), 7.46–7.40 (m, 4 H), 7.38–7.31 (m, 4 H), 7.24–7.20 (m,
Synthesis of HBndpp 7a: Boc-Phe-OBndpp 5a (100 mg) was dis-
solved in a mixture of methanol (5 mL) and 10 % Pd/C (20 mg). The
Eur. J. Org. Chem. 2016, 1714–1719
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