Diimine Reduction of C=C Double Bonds
1 H, NH Phe), 7.87 (d, J = 7.5 Hz, 2 H, Ar-H Fmoc), 7.78 (d, J =
8.2 Hz, 1 H, NH Nva), 7.70 (m, 2 H, Ar-H Fmoc), 7.40 (m, 3 H,
1 NH Ser, 2 Ar-H Fmoc), 7.30 (m, 2 H, Ar-H Fmoc), 7.18 (m, 5
H, Ar-H Phe), 4.35–4.22 (m, 5 H, 1 α-H Phe, 1 α-H Nva, 1 CH
Fmoc, 2 CH2 Fmoc), 4.10 (m, 1 H, α-H Ser), 3.03 (dd, J = 13.5
and 5.0 Hz, 1 H, β-H Phe), 2.87 (dd, J = 13.5 and 8.5 Hz, 1 H, β-
H Phe), 1.55–1.39 (m, 2 H, β-H Nva), 1.22 (m, 2 H, γ-H Nva),
[M + 1]+. C40H40N4O6 (672.29): calcd. C 71.41, H 5.99, N 8.33;
found C 71.52 H 5.85, N 8.47.
Fmoc-Met-Nva-Phe-OH (25): Amorphous solid (7 mg,75% yield).
1H NMR (300 MHz, [D6]DMSO): δ = 8.00 (d, J = 7.3 Hz, 1 H,
NH Phe), 7.86 (m, 3 H, 2 H Ar-H Fmoc, 1 H NH Nva), 7.70 (t, J
= 6.3 Hz, 2 H, Ar-H Fmoc), 7.55 (d, J = 8.1 Hz, 1 H, NH Met),
7.40 (t, J = 7.4 Hz, 2 H, Ar-H Fmoc), 7.31 (t, J = 7.4 Hz, 2 H, Ar-
H Fmoc), 7.18 (m, 5 H, Ar-H Phe), 4.34–4.07 (m, 6 H, 1 α-H Phe,
1 α-H Nva, 1 α-H Met, 1 CH Fmoc, 1 CH2 Fmoc), 3.03 (dd, J =
13.9 and 5.1 Hz, 1 H, β-H Phe), 2.87 (dd, J = 13.9 and 8.2 Hz, 1
H, β-H Phe), 2.41 (m, 2 H, γ-H Met), 2.01 (s, 3 H, ε-H Met), 1.80
(m, 2 H, β-H Met), 1.55–1.41 (m, 2 H, β-H Nva), 1.22 (m, 2 H, γ-
H Nva), 0.80 (t, J = 7.1 Hz, 3 H, δ-H Nva) ppm. 13C NMR
(75 MHz, [D6]DMSO): δ = 172.6 (CO), 171.3 (CO), 171.7 (CO),
155.9 (CO), 143.9 (Ar-C Fmoc), 143.7 (Ar-C Fmoc), 140.7 (Ar-C
Fmoc), 137.7 (Ar-C Phe), 129.1 (Ar-CH Phe), 128.0 (Ar-CH Phe),
127.6 (Ar-CH Fmoc), 127.0 (Ar-CH Fmoc), 126.2 (Ar-CH Phe),
125.3 (Ar-CH Fmoc), 120.1 (Ar-CH Fmoc), 65.6 (CH2 Fmoc), 53.8
(α-C Met), 53.6 (α-C Phe), 52.2 (α-C Nva), 46.6 (CH Fmoc), 36.7
(β-C Phe), 34.4 (β-C Nva), 31.7 (β-C Met), 29.7 (γ-H Met), 18.4
1.07 [s, 9 H, C(CH3)], 0.79 (t, J = 6.9 Hz, 3 H, δ-H Nva) ppm. 13
C
NMR (75 MHz, [D6]DMSO): δ = 173.0 (CO), 171.6 (CO), 169.8
(CO), 156.3 (CO), 144.2 (Ar-C Fmoc), 144.1 (Ar-C Fmoc), 141.1
(Ar-C Fmoc), 138.0 (Ar-C Phe), 129.5 (Ar-CH Phe), 128.4 (Ar-CH
Phe), 128.0 (Ar-CH Phe), 127.4 (Ar-CH Fmoc), 126.6 (Ar-CH
Phe), 125.7 (Ar-CH Fmoc), 120.5 (Ar-CH Fmoc), 73.2 [C(CH3)],
66.1 (CH2 Fmoc), 62.3 (β-C Ser), 55.8 (α-C Ser), 54.0 (α-C Phe),
52.5 (α-C Nva), 47.0 (CH Fmoc), 37.1 (β-C Phe), 35.0 (β-C Nva),
27.5 [C(CH3)], 18.5 (γ-C Nva), 14.1 (δ-C Nva) ppm. HPLC–MS:
tR = 11.35 min (gradient from 40 to 100% A in 15 min); m/z =
630.72 [M + 1]+. C36H43N3O7 (629.31): calcd. C 66.86, H 6.88, N
6.67; found C 66.75, H 6.96, N 6.75.
Fmoc-Ser(Bz)-Nva-Phe-OH (23): Amorphous solid (8 mg, 87%
(γ-C Nva), 14.6 (ε-C Met), 13.7 (δ-C Nva) ppm. HPLC–MS: tR
=
1
yield). H NMR (300 MHz, [D6]DMSO): δ = 8.06 (d, J = 7.2 Hz,
9.98 min (gradient from 40 to 100% A in 15 min); m/z = 618.69 [M
+ 1]+. C34H39N3O6S (617.26): calcd. C 66.10, H 6.36, N 6.80; found
C 66.22 H 6.25, N 6.98.
1 H, NH Phe), 7.92 (d, J = 8.1 Hz, 1 H, NH Nva), 7.87 (d, J =
7.5 Hz, 2 H, Ar-H Fmoc), 7.70 (m, 2 H, Ar-H Fmoc), 7.62 (d, J =
8.3 Hz, 1 H, NH Ser), 7.39 (t, J = 7.6 Hz, 2 H, Ar-H Fmoc), 7.28–
7.21 (m, 7 H, 2 Ar-H Fmoc, 5 Ar-H Bz), 7.19 (m, 5 H, Ar-H Phe),
Ac-Nva-Phe-OH (26): Amorphous solid (5 mg, 98% yield). 1H
4.45 [s, 2 H, Ser(CH2-Bz)], 4.37–4.21 (m, 6 H, 1 α-H Phe, 1 α-H NMR (300 MHz, [D6]DMSO): δ = 8.05 (d, J = 7.8 Hz, 1 H, NH
Nva, 1 α-H Ser, 1 CH Fmoc, 1 CH2 Fmoc), 3.55 (m, 2 H, β-H
Ser), 3.01 (dd, J = 13.8 and 5.3 Hz, 1 H, β-H Phe), 2.85 (dd, J =
13.8 and 8.4 Hz, 1 H, β-H Phe), 1.6–1.40 (m, 2 H, β-H Nva), 1.22
Phe), 7.88 (d, J = 8.3 Hz, 1 H, NH Nva), 7.21 (m, 5 H, Ar-H Phe),
4.37 (m, 1 H, α-H Phe), 4.23 (m, 1 H, α-H Nva), 3.03 (dd, J = 13.8
and 5.2 Hz, 1 H, β-H Phe), 2.88 (dd, J = 13.8 and 8.7 Hz, 1 H, β-
(m, 2 H, γ-H Nva), 0.78 (t, J = 7.1 Hz, 3 H, δ-H Nva) ppm. 13C H Phe), 1.79 (s, 3 H, COCH3), 1.52 (m, 1 H, β-H Nva), 1.41 (m, 1
NMR (75 MHz, [D6]DMSO): δ = 173.1 (CO), 171.6 (CO), 169.6
H, β-H Nva), 1.23 (m, 2 H, γ-H Nva), 0.82 (t, J = 7.2 Hz, 3 H, δ-
(CO), 156.3 (CO), 144.2 (Ar-C Fmoc), 144.1 (Ar-C Fmoc), 141.1 H Nva) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 173.2 (CO),
(Ar-C Fmoc), 138.6 (Ar-C), 137.9 (Ar-C), 129.5 (Ar-CH Phe), 172.2 (CO), 169.4 (CO), 137.9 (Ar-C Phe), 129.5 (Ar-CH Phe),
128.5 (Ar-CH), 128.5 (Ar-CH), 128.0 (Ar-CH), 127.8 (Ar-CH), 128.5 (Ar-CH Phe), 126.7 (Ar-CH Phe), 53.8 (α-C Phe), 52.7 (α-C
127.7 (Ar-CH), 126.7 (Ar-CH), 125.6 (Ar-CH Fmoc), 120.5 (Ar- Nva), 36.9 (β-C Phe), 34.3 (β-C Nva), 22.8 (COCH3), 18.8 (γ-C
CH Fmoc), 72.4 [Ser(CH2-Bz)], 70.3 (β-C Ser), 66.2 (CH2 Fmoc),
55.2 (α-C Ser), 53.8 (α-C Phe), 52.6 (α-C Nva), 47.0 (CH Fmoc),
37.0 (β-C Phe), 34.8 (β-C Nva), 18.6 (γ-C Nva), 14.1 (δ-C Nva)
ppm. HPLC–MS: tR = 11.49 min (gradient from 40 to 100% A in
15 min); m/z = 664.74 [M + 1]+. C39H41N3O7 (663.29): calcd. C
70.57, H 6.23, N 6.33; found C 70.48 H 6.31, N 6.42.
Nva), 14.0 (δ-C Nva) ppm. HPLC–MS: tR = 9.98 min (gradient
from 5 to 80% A in 15 min); m/z = 307.37 [M + 1]+. C16H22N2O4
(306.16): calcd. C 62.73, H 7.24, N 9.14; found C 62.79 H 7.18, N
9.25.
Boc-Nva-Phe-OH (27): Amorphous solid (5 mg, 97% yield). 1H
NMR (300 MHz, [D6]DMSO): δ = 7.91 (d, J = 7.9 Hz, 1 H, NH
Phe), 7.21 (m, 5 H, Ar-H Phe), 6.77 (d, J = 8.2 Hz, 1 H, NH Nva),
4.41 (m, 1 H, α-H Phe), 3.87 (m, 1 H, α-H Nva), 3.03 (dd, J = 13.8
and 5.0 Hz, 1 H, β-H Phe), 2.88 (dd, J = 13.8 and 8.6 Hz, 1 H, β-
H Phe), 1.43 (m, 2 H, β-H Nva), 1.35 [s, 9 H, COC(CH3)3], 1.23
(m, 2 H, γ-H Nva), 0.79 (t, J = 7.2 Hz, 3 H, δ-H Nva) ppm. 13C
NMR (75 MHz, [D6]DMSO): δ = 173.2 (CO), 172.4 (CO), 155.5
(CO), 137.7 (Ar-C Phe), 129.5 (Ar-CH Phe), 128.5 (Ar-CH Phe),
126.7 (Ar-CH Phe), 78.4 [COC(CH3)3], 54.4 (α-C Nva), 53.5 (α-C
Phe), 37.1 (β-C Phe), 34.5 (β-C Nva), 28.5 [COC(CH3)3], 18.9 (γ-
C Nva), 14.0 (δ-C Nva) ppm. HPLC–MS: tR = 13.67 min (gradient
from 5 to 80% A in 15 min); m/z = 365.45 [M + 1]+. C19H28N2O5
(364.20): calcd. C 62.62, H 7.74, N 7.69; found C 62.75 H 7.61, N
7.86.
Fmoc-Trp-Nva-Phe-OH (24): Amorphous solid (6 mg, 60% yield).
1H NMR (300 MHz, [D6]DMSO): δ = 10.84 (s, 1 H, Ar-NH Trp),
8.06 (d, J = 8.1 Hz, 1 H, NH Phe), 7.84 (m, 3 H, 2 Ar-H Fmoc, 1
NH Nva), 7.67 (d, J = 7.6 Hz, 1 H, Ar-H Trp), 7.60 (t, J = 8.2 Hz,
2 H, Ar-H Fmoc), 7.52 (d, J = 8.7 Hz, 1 H, NH Trp), 7.41–7.15
(m, 10 H, 4 Ar-H Fmoc, 1 Ar-H Trp, 5 Ar-H Phe), 7.04 (t, J =
7.3 Hz, 1 H, Ar-H Trp), 6.94 (t, J = 7.3 Hz, 1 H, Ar-H Trp), 6.26
(s, 1 H, Ar-H Trp), 4.24 (m, 3 H, 1 α-H Phe, 1 α-H Nva, 1 α-H
Trp), 4.12 (m, 3 H, 1 CH Fmoc, 1 CH2 Fmoc), 3.13–2.88 (m, 4 H,
2 β-H Phe, 2 β-H Trp), 1.60–1.39 (m, 2 H, β-H Nva), 1.22 (m, 2
H, γ-H Nva), 0.80 (t, J = 7.2 Hz, 3 H, δ-H Nva) ppm. 13C NMR
(75 MHz, [D6]DMSO): δ = 172.1 (CO), 171.4 (CO), 171.0 (CO),
156.1 (CO), 144.1 (Ar-C Fmoc), 140.7 (Ar-C), 138.5 (Ar-C), 136.4
(Ar-C), 129.7 (Ar-CH Phe), 128.3 (Ar-CH), 128.0 (Ar-CH), 127.7 Fmoc-Nva-Phe-NH2 (30): Amorphous solid (16 mg, 99% yield). 1H
(Ar-CH), 127.4 (Ar-CH), 126.4 (Ar-CH Phe), 125.7 (Ar-CH NMR (300 MHz, [D6]DMSO): δ = 8.59 (d, J = 8.2 Hz, 1 H, Ct-
Fmoc), 124.2 (Ar-CH), 121.8 (Ar-C), 121.1 (Ar-CH Trp), 120.4 NH2), 8.03 (m, 1 H, NH Phe), 7.91 (d, J = 7.4 Hz, 2 H, Ar-H
(Ar-CH Fmoc), 119.1 (Ar-CH Trp), 111.6 (Ar-CH Trp), 110.5 (Ar- Fmoc), 7.85 (d, J = 8.2 Hz, 1 H, Ct-NH2), 7.72 (m, 2 H, Ar-H
C), 66.0 (CH2 Fmoc), 55.8 (α-C Phe), 54.5 (α-C Trp), 53.0 (α-C
Fmoc), 7.44 (m, 3 H, 2 Ar-H Fmoc, 1 NH Nva), 7.35 (t, J = 7.4 Hz,
Nva), 46.9 (CH Fmoc), 37.2 (β-C Phe), 34.7 (β-C Nva), 28.1 (β-C 2 H, Ar-H Fmoc), 7.20 (m, 5 H, Ar-H Phe), 4.47 (m, 1 H, α-H
Trp), 18.8 (γ-C Nva), 14.1 (δ-C Nva) ppm. HPLC–MS: tR
10.32 min (gradient from 40 to 100% A in 15 min); m/z = 673.76
=
Phe), 4.26 (m, 3 H, CH Fmoc, CH2 Fmoc), 3.91 (m, 1 H, α-H
Nva), 3.02 (dd, J = 13.7 and 4.7 Hz, 1 H, β-H Phe), 2.84 (dd, J =
Eur. J. Org. Chem. 2009, 4149–4157
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4155