1740
I. MOMOSE et al.
OCH2Ph), 6.01 (1H, d, J ¼ 7:2 Hz, NH), 6.34 (1H, d,
J ¼ 8:4 Hz, NH), 6.60 (1H, d, J ¼ 8:8 Hz, NH), 6.90
(2H, d, J ¼ 8:8 Hz, Tyr-"-H ꢃ 2), 6.98 (2H, d,
J ¼ 8:8 Hz, Tyrol-"-H ꢃ 2), 7.11 (2H, d, J ¼ 8:8 Hz,
Tyr-ꢃ-H ꢃ 2), 7.19 (2H, d, J ¼ 8:8, Tyr-ꢃ-H ꢃ 2), 7.30–
7.40 (5H, m, Ph-H5).
(N-t-Butoxycarbonyl-O-benzyl)-L-tyrosyl-L-valyl-(O-
methyl)-L-tyrosinol (13). Compound 13 was synthesized
by a similar procedure to that for 12þin an 82% yield
1
from 4. APCI-MS m=z 634 ðM þ HÞ . H-NMR (400
MHz, CDCl3) ꢃ: 0.75 (3H, d, J ¼ 6:8 Hz, CH3), 0.85
(3H, d, J ¼ 6:8 Hz, CH3), 1.43 (9H, s, C(CH3)3), 2.23
(1H, m, Val-ꢁ-H), 2.73 (1H, dd, J ¼ 6:8, 13.7 Hz, Tyrol-
ꢁ-H), 2.81 (1H, dd, J ¼ 8:0, 13.7 Hz, Tyrol-ꢁ-H), 2.98
(1H, dd, J ¼ 7:0, 14.2 Hz, Tyr-ꢁ-H), 3.06 (1H, dd,
J ¼ 5:9, 14.2 Hz, Tyr-ꢁ-H), 3.50 (1H, dd, J ¼ 6:1,
11.2 Hz, CHCH2O), 3.66 (1H, dd, 2.5, 11.2 Hz), 3.76
(3H, s, OCH3), 4.13 (2H, m, Tyrol-ꢀ-H, Val-ꢀ-H), 4.23
(1H, dd, J ¼ 6:1, 12.0 Hz, Tyr-ꢀ-H), 4.93 (1H, d,
J ¼ 4:9 Hz, NH), 5.03 (2H, s, OCH2Ph), 6.35 (1H, br,
NH), 6.55 (1H, br, NH), 6.80 (2H, d, J ¼ 8:8 Hz, Tyr-"-
H ꢃ 2), 6.93 (2H, d, J ¼ 8:8 Hz, Tyrol-"-H ꢃ 2), 7.11
(2H, d, J ¼ 8:8 Hz, Tyr-ꢃ-H ꢃ 2), 7.12 (2H, d, J ¼
8:8 Hz, Tyrol-ꢃ-H ꢃ 2), 7.30–7.40 (5H, m, Ph-H5).
(N-t-Butoxycarbonyl-O-acetyl)-L-tyrosyl-L-valyl-(O-
acetyl-O-methyl)-L-tyrosinol (14). Compound 14 was
synthesized by a similar procedure to that for 5 and 6
in a 92% yield from 13. APCI-MS m=z 628 ðM þ HÞþ.
1H-NMR (400 MHz, CDCl3) ꢃ: 0.79 (3H, d, J ¼ 7:2 Hz,
CH3), 0.86 (3H, d, J ¼ 7:2 Hz, CH3), 1.42 (9H, s,
C(CH3)3), 2.07 (3H, s, COCH3), 2.14 (1H, m, Val-ꢁ-H),
2.26 (3H, s, COCH3), 2.70 (1H, dd, J ¼ 8:0, 14.0 Hz,
Tyrol-ꢁ-H), 2.80 (1H, dd, J ¼ 6:0, 14.0 Hz, Tyrol-ꢁ-H),
3.08 (2H, m, Tyr-ꢁ-H2), 3.77 (3H, s, OCH3), 4.03 (2H,
d, J ¼ 5:2 Hz, CHCH2O), 4.13 (1H, m, Val-ꢀ-H), 4.30
(1H, m, Tyr-ꢀ-H), 4.38 (1H, m, Tyrol-ꢀ-H), 4.92 (1H, d,
J ¼ 6:4 Hz, NH), 6.25 (1H, b, NH), 6.52 (1H, d, J ¼
8:4 Hz, NH), 6.82 (2H, d, J ¼ 8:6 Hz, Tyr-"-H ꢃ 2),
7.02 (2H, d, J ¼ 8:6 Hz, Tyrol-"-H ꢃ 2), 7.09 (2H, d,
J ¼ 8:6 Hz, Tyr-ꢃ-H ꢃ 2), 7.20 (2H, d, J ¼ 8:6 Hz,
Tyrol-ꢃ-H ꢃ 2).
Isovaleryl-(O-benzyl)-L-tyrosyl-L-valyl-(O-methyl)-L-
tyrosinol (12). Compound 11 was deacetylated by a
similar procedure to that for 9. To a solution of
deacetylated 11 (172 mg, 0.28 mmol) in 6 ml of MeOH
was added 2 ml of CHCl3, 14.8 mg of N,N-diisopropyl-
ethylamine (DIEA, 0.11 mmol) and 300 mg of trimeth-
ylsilyldiazomethane (2.63 mmol). The reaction mixture
was stirred for 24 h at room temperature. The solvent
was evaporated to give 12 (294 mg) as a white powder
in a quantitative yield from 11. APCI-MS m=z: 618
ðM þ HÞþ, 616 ðM þ HÞꢂ. 1H-NMR (400 MHz,
CD3OD) ꢃ: 0.81 (3H, d, J ¼ 6:4 Hz, CH3), 0.85 (3H,
d, J ¼ 6:8 Hz, CH3), 0.86 (3H, d, J ¼ 6:4 Hz, CH3),
0.89 (3H, d, J ¼ 6:8 Hz, CH3), 1.97–2.02 (4H, m, Val-ꢁ-
H, (CH3)2CHCH2CO), 2.71 (1H, dd, J ¼ 7:2, 14.0 Hz,
Tyrol-ꢁ-H), 2.82 (2H, m, Tyrol-ꢁH, Tyr-ꢁ-H), 3.03 (1H,
dd, J ¼ 5:8, 14.2 Hz, Tyr-ꢁ-H), 3.49 (2H, m, CHCH2O),
3.72 (3H, s, OCH3), 4.05 (1H, m, Tyrol-ꢀ-H), 4.07 (1H,
d, J ¼ 7:2 Hz, Val-ꢀ-H), 4.61 (1H, dd, J ¼ 6:0, 8.8 Hz,
Tyr-ꢀ-H), 5.00 (2H, s, OCH3Ph), 6.79 (2H, d, J ¼
8:8 Hz, Tyr-"-H ꢃ 2), 6.88 (2H, d, J ¼ 8:8 Hz, Tyrol-"-
H ꢃ 2), 7.12 (2H, d, J ¼ 8:8 Hz, Tyr-ꢃ-H ꢃ 2), 7.14
(2H, d, J ¼ 8:8, Tyrol-ꢃ-H ꢃ 2), 7.30–7.40 (5H, m,
Ph-H5).
Isovaleryl-L-tyrosyl-L-valyl-(O-methyl)-DL-tyrosinal
(TP-106). TP-106 was synthesized by a similar proce-
dure to that for 5 and TP-104 in a 38% yield from 12.
24
Mp 145–147 ꢀC. ½ꢀꢁD ꢂ32:1ꢀ (c 0.43, MeOH). Rf
0.50 (CHCl3/MeOH = 10/1). APCI-MS m=z: 526
ðM þ HÞþ, 524 ðM ꢂ HÞꢂ. HRFAB-MS m=z: calcd. for
C29H40O6N3, 526.2917; found, 526.2917 ðM þ HÞþ. IR
(KBr) ꢂmax cmꢂ1: 3280, 2960, 1735, 1635, 1545, 1515,
1-Naphthylacetyl-L-tyrosyl-L-valyl-(O-methyl)-DL-tyro-
sinal (TP-108). TP-108 was synthesized by a similar
procedure to that for 7, 9 and TP-104 in a 64% yield
26
1
1245, 1035, 830. H-NMR (400 MHz, CD3OD) ꢃ: 0.75
from 14. Mp 208–210 ꢀC. ½ꢀꢁD
ꢂ27:4ꢀ (c 0.19,
(3H, d, J ¼ 6:4 Hz, CH3), 0.81 (3H, d, J ¼ 6:4 Hz,
CH3), 0.86 (3H, d, J ¼ 6:8 Hz, CH3), 0.89 (3H, d,
J ¼ 6:8 Hz, CH3), 1.90 (1H, m, (CH3)2CHCH2), 1.98
(1H, m, Val-ꢁ-H), 1.99 (2H, d, J ¼ 6:8 Hz, CH2CO),
2.61–2.75 (2H, m, Tyr-ꢁ-H, Tyral-ꢁ-H), 2.89–3.05 (2H,
m, Tyr-ꢁ-H, Tyral-ꢁ-H), 3.65 (3H, s, OCH3), 4.06–4.14
(2H, m, Tyral-ꢀ-H, Val-ꢀ-H), 4.44 (1H, dd, J ¼ 4:2,
7.0 Hz, hemiacetal-H), 4.59 (1H, m, Tyr-ꢀ-H), 6.67 (2H,
m, Tyr-"-H ꢃ 2), 6.77 (2H, d, J ¼ 8:2 Hz, Tyral-"-
H ꢃ 2), 7.04 (2H, m, Tyr-ꢃ-H ꢃ 2), 7.11 (2H, d, J ¼
8:2 Hz, Tyral-ꢃ-H ꢃ 2). 13C-NMR (100 MHz, CD3OD)
ꢃ: 17.7 (CH3), 18.1 (CH3), 22.3 (CH3), 22.4 (CH3), 26.2
(CH3)2CHCH2), 30.7 (Val-ꢁ-CH), 34.3 (Tyral-ꢁ-CH2),
37.1 (Tyr-ꢁ-CH2), 45.6 (CH2CO), 54.5 (Tyral-ꢀ-CH),
55.3 (OCH3), 55.6 (Tyr-ꢀ-CH), 59.2 (Val-ꢀ-CH), 96.9
(hemiacetal-C), 114.0 (Tyr-"-CH), 115.6 (Tyral-"-CH),
127.4 (Tyr-ꢄ-C), 129.8 (Tyral-ꢄ-C), 130.0 (Tyr-ꢃ-CH),
130.2 (Tyral-ꢃ-CH), 155.9 (Tyral-ꢅ-C), 158.3 (Tyr-ꢅ-C),
171.7 (Val-CO), 172.8 (Tyr-CO), 173.6 (CH2CO).
MeOH). Rf 0.47 (CHCl3/MeOH = 10/1). APCI-MS
m=z: 610 ðM þ HÞþ, 608 ðM ꢂ HÞꢂ. HRFAB-MS m=z:
calcd. for C36H40O6N3, 610.2917; found, 610.2930
ðM þ HÞþ. IR (KBr) ꢂmax cmꢂ1: 3280, 2960, 1730,
1640, 1540, 1510, 1250, 780. 1H-NMR (400 MHz,
CDCl3/CD3OD) ꢃ: 0.75 (3H, dd, J ¼ 2:4, 6.8 Hz, CH3),
0.82 (3H, dd, J ¼ 2:4, 6.8 Hz, CH3), 1.94 (1H, m, Val-ꢁ-
H), 2.64–2.72 (2H, m, Tyr-ꢁ-H, Tyral-ꢁ-H), 2.81–2.97
(2H, m, Tyr-ꢁ-H, Tyral-ꢁ-H), 3.66 (3H, d, J ¼ 3:2 Hz,
OCH3), 3.96 (2H, s, CH2CO), 4.03 (1H, t, J ¼ 7:0 Hz,
Tyral-ꢀ-H), 4.12 (1H, m, Val-ꢀ-H), 4.44 (1H, dd,
J ¼ 2:4, 4.0 Hz, hemiacetal-H), 4.56 (1H, m, Tyr-ꢀ-
H), 6.57 (2H, dd, J ¼ 5:6, 8.6 Hz, Tyr-"-H ꢃ 2), 6.76
(4H, m, Tyr-ꢃ-H ꢃ 2, Tyral-"-H ꢃ 2), 7.10 (2H, dd,
J ¼ 2:2, 8.6 Hz, Tyral-ꢃ-H ꢃ 2), 7.27 (1H, d, J ¼ 8:0
Hz, naphthyl-H), 7.40 (1H, t, J ¼ 8:0 Hz, naphthyl-H),
7.48 (2H, m, naphthyl-H2), 7.79 (2H, d, J ¼ 8:0 Hz,
naphthyl-H2), 7.86 (1H, d, J ¼ 8:8 Hz, naphthyl-H).
13C-NMR (100 MHz, CDCl3/CD3OD) ꢃ: 18.2 (CH3),