[0.35 H, m, 1-H2 (E)], 2.95–2.87 [0.65 H, m, 1-H2 (Z)], 2.69 [0.35
H, m, 2-H2 (E)], 2.53 [0.35 H, m, 2-H2 (E)], 2.36 [0.65 H, m, 2-
H2 (Z)], 2.29–2.33 [0.65, m, 2-H2 (Z)], 1.73–1.66 [0.65 H, m, β-
H2 (Z)], 1.57–1.48 [0.65 H, m, β-H2 (Z)], 1.45–1.36 (1 H, m, γ-
H), 1.27–1.26 [0.7 H, m, β-H2 (E)], 0.90–0.84 [3.9 H, m, δ-H3
(Z)], 0.75 [1.05 H, d, J 6.1, δ-H3 (E)] and 0.71 [1.05 H, d, J 6.2,
δ-H3 (E)].
Ná-[3-(Benzylthio)propyl]-Ná-Fmoc-phenylalanine
11m.
(CDCl3; 298 K; isomer ratio E :Z = 1:4.00) 9.00 (1 H, br s,
CO2H), 7.65–7.62 (2 H, m, Fmoc 4- and 5-H), 7.54–7.42 (2 H, m,
Fmoc 1- and 8-H), 7.31–7.08 (12.6 H, m, ArH), 7.11–6.99 (1 H,
m, ArH), 6.65–6.64 (0.4 H, m, ArH), 4.78 [0.2 H, dd, J12 4.3, J22
10.6, Fmoc CH2 (E)], 4.56 [0.8 H, dd, J12 5.7, J22 10.7, Fmoc
CH2 (Z)], 4.47 [0.2 H, dd, J12 4.3, J22 10.6, Fmoc CH2 (E)], 4.36
[0.8 H, dd, J12 5.8, J22 10.7, Fmoc CH2 (Z)], 4.14–4.08 (1 H, m,
Fmoc CH), 3.93 [0.8 H, d, J1 5.4, J2 9.9, α-H (Z)], 3.77 [0.2 H,
m, α-H (E)], 3.47 [0.4 H, s, PhCH2 (E)], 3.44 [1.6 H, s, PhCH2
(Z)], 3.25–3.14 [1.6 H, m, β-H2 (Z)], 3.03–3.00 [0.2 H, m, 1-H2
(E)] 2.90–2.79 [0.8 H, m, 1-H2 (Z)], 2.53–2.50 [0.2 H, m, 1-H2
(E)], 2.46–2.39 [0.8 H, m, 1-H2 (Z)], 2.31 [0.4 H, m, β-H2 (E)],
2.17–2.12 [0.4 H, m, 3-H2 (E)], 2.09–1.89 [1.6 H, m, 3-H2 (Z)],
1.37–1.34 [0.4 H, m, 2-H2 (E)] and 1.24–1.12 [1.6 H, m, 2-H2
(Z)].
Ná-[3-(Benzylthio)propyl]-Ná-Fmoc-leucine 11g. δH (CDCl3;
298 K; isomer ratio E :Z = 1:2.33) 9.79 (1 H, br s, CO2H),
7.60 (2 H, d, J 7.4, Fmoc 4- and 5-H), 7.44 (2 H, d, J 3.6, Fmoc
1- and 8-H), 7.26–7.11 (9 H, m, PhCH2 and Fmoc 2-, 3-, 6- and
7-H), 4.53–4.49 (2 H, m, Fmoc, CH2), 4.36 (1 H, dd, J1 5.0, J2
7.5, α-H), 4.10–4.06 (1 H, m, Fmoc CH), 3.56 [0.6 H, s, PhCH2
(E)], 3.49 (1.4 H, s, PhCH2 (Z)], 3.33 [0.6 H, m, 1-H2 (E)], 2.98
[0.7 H, m, 1-H2 (Z)], 2.73 [0.7 H, m, 1-H2 (Z)], 2.26 [0.6 H, m, 3-
H2 (E)], 2.05–1.98 [1.4 H, m, 3-H2 (Z)], 1.63 [0.6 H, m, 2-H2 (E)],
1.55 (2 H, m, β-H2), 1.41–1.35 [2.4 H, m, 2-H2 (Z) and γ-H],
0.81 [2.1 H, d, J 6.1, δ-H3 (Z)], 0.80 [2.1 H, d, J 6.4, δ-H3 (Z)],
0.71 [0.9 H, d, J 5.6, δ-H3 (E)] and 0.66 [0.9 H, d, J 5.6, δ-H3 (E)].
Ná-[3-(Boc-amino)propyl]-Ná-Fmoc-leucine 11h. δH (CDCl3;
298 K) 7.76 (2 H, m, Fmoc 4- and 5-H), 7.57 (2 H, d, J 7.4,
Fmoc 1- and 8-H), 7.39 (2 H, m, Fmoc 3- and 6-H), 7.32 (2 H,
m, Fmoc 2- and 7-H), 4.66 (2 H, m, Fmoc CH2), 4.52 (0.5 H, m,
Fmoc CH), 4.38 (0.5 H, m, Fmoc CH), 4.22 (1 H, m, α-H), 3.41
(1 H, m, 1-H2), 3.03–2.89 (3 H, m, 1-H and 3-H2), 2.77 (2 H,
m, β-H2), 1.62 (2 H, m, 2-H2), 1.43 (9 H, s, But), 1.25 (1 H, m, γ-
H) and 0.88–0.77 (6 H, m, δ-H3).
Ná-[3-(Boc-amino)propyl]-Ná-Fmoc-phenylalanine 11n. The
1H NMR spectrum was identical with that of the compound
which was previously prepared by the nucleophilic substitution
method.26
O-benzyl-Ná-[3-(Boc-amino)propyl]-Ná-Fmoc-serine
11o.
δH (CDCl3; 298 K; not enough resolution to determine the iso-
mer ratio) 7.76–7.72 (2 H, m, Fmoc 4- and 5-H), 7.56–7.50 (2
H, m, Fmoc 1- and 8-H), 7.41–7.36 (2 H, m, Fmoc 3- and 6-H),
7.35–7.20 (7 H, m, Fmoc 2- and 7-H and PhCH2), 4.54–4.44
(~1 H, m, Fmoc CH2), 4.51 (2 H, s, PhCH2), 4.37–4.34 (~1.25
H, m, Fmoc CH2 and Fmoc CH), 4.28 (~1 H, m, α-H), 4.25–4.22
(~0.25 H, m, Fmoc CH), 3.97–3.95 (~0.5 H, m, Fmoc CH), 3.77
(~0.5 H, m, 1-H2), 3.64 (~1 H, m, β-H2), 3.51 (~0.5 H, m, 1-H2),
3.42 (~1 H, m, β-H2), 3.37–3.27 (~2 H, m, 1-H and 2-H) and
3.06 (~1 H, m, 2-H2).
Ná-[6-(Benzylthio)hexyl]-å-Boc-Ná-Fmoc-lysine
11i.
δH (CDCl3; 298 K; isomer ratio E :Z = 1:2.70) 7.67 (2 H, d, J
7.5, Fmoc 4- and 5-H), 7.49 (2 H, d, J 7.5, Fmoc 1- and 8-H),
7.33–7.29 (2 H, m, Fmoc 3- and 6-H), 7.24–7.19 (5 H, m,
PhCH2), 7.18–7.16 (2 H, m, Fmoc 2- and 7-H), 4.59–4.53 (2 H,
m, Fmoc CH2), 4.15 (1 H, t, J 5.4, Fmoc CH), 4.11–4.05 [0.73
H, m, α-H (Z)], 3.98 [0.27 H, m, α-H (E)], 3.63 (2 H, s, PhCH2),
3.25 [0.27 H, m, 1-H2 (E)], 3.00 [0.73 H, m, 1-H2 (Z)], 2.99 (2 H,
t, J 6.8, ε-H2), 2.89 [0.27 H, m, 1-H2 (E)], 2.71 [0.73 H, m, 1-H2
(Z)], 2.31 (2 H, t, J 7.3, 6-H2), 1.90 [1.46 H, m, β-H2 (Z)], 1.62
[0.54 H, m, β-H2 (E)], 1.41 (2 H, m, 2-H2), 1.39 [0.54 H, m, δ-H2
(E)], 1.38 [1.46 H, m, δ-H2 (Z)], 1.37 (9 H, s, But), 1.24 (2 H, m,
5-H2), 1.22 [1.46 H, m, 4-H2 (Z)], 1.20 [1.46 H, m, γ-H2 (Z)],
1.19 [0.54 m, γ-H2 (E)], 1.13 [0.54 H, m, 4-H2 (E)] and 0.92 (2 H,
m, 3-H2).
Ná-[4-(Benzylthio)butyl]-Ná-Fmoc-NIn-formyltryptophan 11p.
δH (CDCl3; 298 K; isomer ratio E :Z = 1:1.86) 9.64 [0.35 H, s,
CHO (E)], 9.24 [0.65 H, s, CHO (Z)], 8.24 [0.65 H, s, indole
(Z)], 7.995 [0.35 H, s, indole (E)], 7.65 [2 H, m, Fmoc 4- and 5-
H], 7.58 (1 H, m, indole), 7.44 (2 H, m, Fmoc 1- and 8-H), 7.44
(1 H, m, indole), 7.30 (2 H, m, PhCH2, o-H), 7.29 (2 H, m, Fmoc
3- and 6-H), 7.24 (2 H, m, Fmoc 2- and 7-H), 7.21 (1 H, m,
PhCH2, p-H), 7.19–7.15 (2 H, m, PhCH2, m-H), 7.14 (1 H, m,
indole), 6.92 [0.65 H, indole 8-H (Z)], 6.11 [0.35 H, m, indole
8-H (E)], 3.68 (2 H, s, PhCH2), 3.50 (1 H, m, α-H), 3.19–3.09
(2 H, m, β-H2), 2.77–2.69 (2 H, m, 1-H2), 2.40–2.31 (2 H, m, 4-
H2) and 1.55–1.47 (4 H, m, 2- and 3-H2).
Ná-[4-(Benzylthio)butyl]-Ná-Fmoc-methionine 11j. δH (CDCl3;
298 K; isomer ratio E :Z = 1:2.33) 9.54 (1 H, br s, CO2H), 7.73
(2 H, d, J 7.4, Fmoc 4- and 5-H), 7.56 (2 H, d, J 7.2, Fmoc 1-
and 8-H), 7.40–7.23 (9 H, m, ArH), 4.66–4.57 (2 H, m, Fmoc
CH2), 4.25 (1 H, dd, J1 5.0, J2 9.1, α-H), 4.21 [0.7 H, t, J 5.2,
Fmoc CH (Z)], 4.17 [0.3 H, m, Fmoc CH (E)], 3.68 (2 H, s,
PhCH2), 3.47 [0.3 H, m, 1-H2 (E)], 3.09–3.04 [1 H, m, 1-H2 (E)
and 1-H2 (Z)], 2.84–2.80 [0.7 H, m, 1-H2 (Z)], 2.53–2.48 [0.7 H,
m, γ-H2 (Z)], 2.41 [0.6 H, t, J 6.9, 4-H2 (E)], 2.38–2.30 [2 H, m,
γ-H2 (Z) and β-H2 (E)], 2.27 [1.4 H, t, J 6.8, 4-H2 (Z)], 2.12–2.05
[1.4 H, m, β-H2 (Z)], 2.07 [2.1 H, s, ε-H3 (Z)], 2.02 [0.9 H, s, ε-
H3 (E)], 1.54 [1.4 H, m, 3-H2 (Z)] and 1.34–1.27 [2.6 H, m, 3-H2
(E) and 2-H2].
Ná-[2-(Benzylthio)ethyl]-O-tert-butyl-Ná-Fmoc-tyrosine 11q.
δH (CDCl3; 298 K; resolution too low to determine the isomer
ratio) 7.76–7.71 (2 H, m, Fmoc 4- and 5-H), 7.56–7.50 (2 H, m,
Fmoc 1-and 8-H), 7.41–7.63 (2 H, m, Fmoc 3-and 6-H), 7.34–
7.20 (7 H, m, Fmoc 2- and 7-H and PhCH2), 4.54–4.44 (~1 H, m,
Fmoc CH2), 4.51 (2 H, s, PhCH2), 4.37–4.33 (~1.25 H, m, Fmoc
CH2 and CH), 4.27 (1 H, m, aCH), 4.25–4.22 (~0.25 H, m,
Fmoc CH), 3.97–3.95 (~0.5 H, m, Fmoc CH), 3.76 (0.5 H, m,
1CH2), 3.64 (1 H, m, bCH2), 3.51 (0.5 H, m, 1CH2), 3.42 (1 H, m,
1
2
2
bCH2), 3.36–3.26 (2 H, CH2 and CH2), 3.06 (1 H, m, CH2)
and 1.39 (9 H, s, But).
Ná-[3-(Boc-amino)propyl]-Ná-Fmoc-valine 11r. δH (CDCl3; 298
K) 7.76 (2 H, d, J 7.4, Fmoc 4- and 5-H), 7.76–7.52 (2 H, m,
Fmoc 1- and 8-H), 7.42–7.38 (2 H, m, Fmoc 3- and 6-H), 7.35–
7.31 (2 H, m, Fmoc 2- and 7-H), 4.74 (1 H, m, Fmoc CH2), 4.62
(0.5 H, m, Fmoc CH), 4.46 (0.5 H, m, Fmoc CH), 4.22 (1 H, m,
Fmoc CH2), 3.87 (0.35 H, m, α-H), 3.575 (0.65 H, m, α-H), 3.28
(0.7 H, m, 1-H2), 3.06 (1.3 H, m, 1-H2), 2.80–2.74 (2 H, m,
3-H2), 2.32 (0.65 H, m, β-H), 2.055 (0.35 H, m, β-H), 1.73 (0.7
H, m, 2-H2), 1.44 (9 H, s, But), 1.25 (1.3 H, m, 2CH2), 0.95 (1.95
H, d, J 6.4, γ-CH3), 0.903 (1.05 H, m, γ-H3), 0.724 (1.95 H, d, J
6.4, γ-H3), 0.655 (1.05 H, m, γ-H3).
Ná-[2-(Benzylthio)ethyl]-Ná-Fmoc-phenylalanine
11l.
δH (CDCl3; 298 K; isomer ratio E :Z = 1:4.00) 8.98 (1 H, br s,
CO2H), 7.64–7.61 (2 H, m, Fmoc 4- and 5-H), 7.40–7.38 (2 H,
m, Fmoc 1- and 8-H), 7.27–7.03 (12.6 H, m, ArH), 6.92–6.90
(1 H, m, ArH), 6.58–6.58 (0.4 H, m, ArH), 4.72 [0.2 H, dd, J12
4.4, J22 10.6, Fmoc CH2 (E)], 4.51 [0.8 H, dd, J12 5.9, J22
10.7, Fmoc CH2 (Z)], 4.40 [0.2 H, dd, J12 4.4, J22 10.6, Fmoc
CH2 (E)], 4.30 [0.8 H, dd, J12 6.1, J22 10.7, Fmoc CH2 (Z)],
4.09–4.04 (1 H, m, Fmoc CH), 3.90 [0.8 H, dd, J1 4.6, J2 10.5,
α-H (Z)], 3.76 [0.21 H, m, α-H (E)], 3.470 [0.4 H, s, PhCH2
(E)], 3.31 [1.6 H, s, PhCH2 (Z)], 3.20–3.06 [1.6 H, m, β-H2 (Z)],
2.91 [0.8 H, m, 1-H2 (Z)], 2.78 [0.2 H, m, 1-H2 (E)], 2.62 [0.4 H,
m, β-H2 (E)], 2.50 [0.8 H, m, 1-H2 (Z)], 2.27 [0.2 H, m, 1-H2
(E)], 2.16 [0.4 H, m, 2-H2 (E)] and 2.00–1.90 [1.6 H, m, 2-H2
(Z)].
Method N. Protection of the secondary á-amino group unit of
10 with the Boc group by temporary TMS protection to give 12
This procedure was identical with the latter (Method M) except
for the addition of di-tert-butyl dicarbonate instead of Fmoc-
J. Chem. Soc., Perkin Trans. 1, 1997
1509