4320
Y. Konda et al. / Tetrahedron 57 52001) 4311±4321
+-COO-), 3350 +-OH). HRFABMS m/z: 846.3832
[M1Na]1, Calcd for C41H57N7O9SNa: 846.3836.1H NMR
+400 MHz, pyridine-d5) d: 0.97, 1.00 +each 3H, d, J7.0,
Val3-CH3£2), 1.38 +9H, s, t-Bu-H), 1.71+2H, br, Arg4-H2),
1.82, 1.99 +each 1H, m, Arg3-H2), 2.32 +1H, m, Val3-H),
3.12, 3.23 +each 1H, dd, J13.0, 7.0, PheOH3-H2), 3.22
C-30, 50), 127.27, 127.35, 128.71 +each d, Phe-, PheCHO-,
Bn-arom C-40), 129.00 +d, Mbs-arom C-20, 60), 130.09
+d, PheCHO-arom C-20, 60), 130.36 +d, Phe-arom C-20,
60), 138.06 +s, Phe-arom C-10), 138.30 +s, Mbs-arom
C-10), 157.95, 157.99 +s, Arg C-7), 158.56, 158.59 +s,
ureido-C), 162.64 +s, Mbs-arom C-40), 172.17 +s, Val
C-1), 172.47 +s, Phe C-1), 173.54 +s, Arg C-1), 200.16 +d,
PheCHO C-1).
+2H, br, Phe3-H2), 3.31+2H, br, Arg5-H ), 3.64 +3H, s,
2
Mbs-OCH3), 3.97, 4.00 +each 1H, dd, J11.0, 5.0,
PheOH1-H2), 4.72 +1H, m, PheOH2-H), 4.85 +1H, t,
J8.0, Val2-H), 4.97 +1H, br, Arg2-H), 5.08 +1H, dt,
J8.0, 6.0, Phe2-H), 7.02 +2H, d, J8.5, Mbs-arom-H),
7.12±7.44 +10H, m, Phe, PheOH-arom-H), 7.16 +1H, d,
J8.0, Phe2-NH), 7.47 +1H, d, J8.0, Arg2-NH), 8.27
+2H, d, J8.5, Mbs-arom-H), 9.02 +1H, d,J8.0,
PheOH2-NH). 13C-NMR +100.6 MHz, pyridine-d5) dc:
18.89, 19.89 +each q, Val3-CH3£2), 26.00 +t, Arg C-4),
28.06 +q, t-Bu-CH3), 30.67 +t, Arg C-3), 31.42 +d, Val
C-3), 37.76 +t, PheOH C-3), 39.15 +t, Phe C-3), 41.18 +t,
Arg C-5), 53.83 +d, PheOH C-2), 54.04 +d, Arg C-2), 55.58
+q, Mbs-OCH3), 55.71+d, Phe C-2), 59.68 +d, Val C-2),
63.57 +t, PheOH C-1), 81.47 +s, t-Bu-OC+CH3)3), 114.29
+d, Mbs-arom C-30, 50), 126.57, 127.0 +each d, Phe-,
PheOH±arom C-40), 128.69 +d, Mbs-arom C-20, 60),
128.76, 128.81 +each d, Phe-, PheOH-arom C30, 50),
130.01, 130.18 +each d, Phe-, PheOH-arom C20, 60),
137.67 +s, Phe-arom C-10), 138.35 +s, Mbs-arom C-10),
139.68 +s, PheOH-arom C-10), 158.22 +s, Arg C-7), 158.81
+s, ureido-C), 162.19 +s, Mbs-arom C-40), 172.37 +s, Phe
C-1), 172.54 +s, Val C-1), 173.64 +s, Arg C-1).
7.1.19. Mixture of a and b-MAPI 32 and 3). The
compound 26 +30.0 mg, 36.5 mmol) was dissolved in
methanesulfonic acid +184 ml, 2.80 mmol) and anisole
+9 ml, 84 mmol) was added. The mixture was stirred for
40 min. Ether +6 ml£3) was added to the reaction mixture
and decanted. Concentration of ether insoluble portion gave
light yellow oil +38.2 mg) which was puri®ed by column
chromatography +Amberlite IRA-410 acetone form, eluated
with water), followed by Sephadex LH-20 column chroma-
tography +eluated with MeOH) to afford colorless grannules
+2 and 3)+10.0 mg, 46%). 2 and 3: Rf0.72 +MeOH/
AcOH100: 1), mp 189±1988 +lit., 2: 204±2054c; 3: 221±
2124e); [a]D2526.38 +c0.32, AcOH) +lit., 2: 218, c1.0,
AcOH12c; 3: 0, c1, AcOH12e). HRFABMS m/z: 596.3188
[M1H]1, Calcd for C30H42N7O6: 596.3197. 1H NMR
+400 MHz, DMSO-d6) d: 0.65 +3H, d, J7.0, Val3-CH3),
0.69 +3H, d, J6.8, Val3-CH3), 0.75 +3H, dd, J7.0, 1.3,
Val30*-CH3), 0.78 +3H, dd, J7.0, 2.0, Val30-CH3), 1.36
+2H, m, Arg3-Ha, Arg30-Ha), 1.42 +4H, m, Arg4-H2,
Arg40-H2), 1.66 +2H, m, Arg3-Hb, Arg30-Hb), 1.82 +1H,
quint, Val3-H), 1.92 +1H, quint, Val30-H), 2.72 +2H, dd,
J14.0, 10.0, PheCHO3-Ha, PheCHO30-Ha), 2.80 +2H,
dd, J10.5, 5.0, Phe3-Ha, Phe30-Ha), 2.94 +2H, m, Phe3-
Hb, Phe30-Hb), 2.97, 3.05 +each 2H, m, Arg5-H2, Arg50-H2),
3.14 +2H, dd, J14.0, 6.0, PheCHO3-Hb, PheCHO30-Hb),
3.96 +2H, m, Phe2-H, Phe20-H), 4.14 +2H, m, Val2-H,
Val20-H), 4.16 +2H, m, Arg2-H, Arg20-H), 4.32 +2H, m,
PheCHO2-H, PheCHO20-H), 6.05 +2H, d, J7.0, Phe2-
NH, Phe20-NH), 6.58, 6.60 +each 1H, d, J9.0, Arg2-NH,
Arg20-NH), 7.04-7.31+01H, m, Phe, PheCHO-arom-H),
7.28-7.86 +6H, br, -C+NH)-NH2), 7.66, 7.71+each 1H, d,
J9.0, Val2-NH, Val20-NH), 8.50 +2H, d, J7.5,
PheCHO2-NH, PheCHO20-NH), 8.80 +2H, br, Arg6-NH,
Arg60-NH), 9.42, 9.47 +each 1H, brs, PheCHO1-H,
PheCHO10-H). 13C-NMR +100.6MHz, DMSO-d6) d:
17.37, 19.14 +each q, Val3-CH3£2), 17.52, 19.04 +each q,
Val30-CH3£2), 24.60, 24.64 +each t, Arg C-4, Arg C0-4),
29.15, 29.19 +each t, Arg C-3, Arg C0-3), 30.47 +d, Val
C-3, Val C0-3), 33.25, 33.33 +each t, PheCHO C-3, PheCHO
C0-3), 38.34, 38.36 +each t, Phe C-3, Phe C0-3), 40.20 +t, Arg
C-5, Arg C0-5), 52.46 +d, Arg C-2, Arg C0-2), 56.53, 56.58
+each d, Phe C-2, Phe C0-2), 57.21, 57.30 +each d, Val C-2,
Val C0-2), 59.46, 59.72 +each d, PheCHO C-2, PheCHO
C0-2), 125.43, 126.19, 127.59, 128.12, 128.15, 128.99,
129.11, 129.39 +each d, Phe, PheOH-arom C-20, 30, 40, 50,
60, C0-20, 30, 40, 50, 60), 137.44, 137.59 +each s, Phe-arom
C-10, C0-10), 139.36, 139.39 +each s, PheCHO-arom C-10,
C0-10), 157.27 +s, ureido-C, C0), 157.90, 157.95 +each s, Arg
C-7, Arg C0-7), 171.30, 171.36 +each s, Val C-1, Val C0-1),
172.19 +s, Arg C-1, Arg C0-1), 175.65 +s, Phe C-1, Phe
C0-1), 200.01, 200.07 +s, PheCHO C-1, PheCHO C0-1).
*The sign of H0 and C0 shows one of the diastereoisomer
in accordance with the other isomer which is described as H
and C.
7.1.18. Oxidation of tetrapeptide 25. PDC +51mg,
0.13 mmol), 4A-MS +300 mg), celite 545 +300 mg) were
added to the solution of 25 +100 mg, 0.12 mmol) in
CH2Cl2 +12 ml) and stirred for 3.5 h at room temperature
under argon. The reaction mixture was puri®ed by ¯ash
column chromatography +Silica gel, CHCl3/MeOH20:1)
to afford colorless plates 26 +63 mg, 63%). mp 107±1148C
+MeOH). Rf0.36 +CHCl3/MeOH20:1). [a]D27222.138
+c0.47, CHCl3)IR +CHCl3) ymax cm21: 1590 +arom),
1630 +-NHCONH-), 1650 +-NHCO-), 1710 +-CHO), 1730
+-COO-).HRFABMS m/z: 822.3828 [M1H]1, Calcd for
C41H56N7O9S: 822.3860 [M1H]. 1H NMR +400 MHz,
acetone-d6) d: 0.83, 0.86 +each 3H, d, J7.0, Val3-
CH3£2), 1.39 +9H, s, t-butyl-H), 1.57 +2H, br, Arg4-H2),
1.58 +1H, br, Arg3-Ha), 1.77 +1H, m, Arg3-Hb), 2.08 +1H,
m, Val3-H), 2.97 +1H, dd, J15.0, 9.0, Phe3-Ha), 2.99, 3.03
+each 1H, dd, J14.0, 6.0, PheCHO3-H2), 3.24 +1H, dd,
J15.0, 5.0, Phe3-Hb), 3.25 +2H, br, Arg5-H2), 3.86 +3H,
s, Mbs-OCH3), 4.29 +1H, dd, J9.0, 6.0, Val2-H), 4.33 +1H,
br, Arg2-H), 4.52 +1H, m, Phe2-H), 4.55 +1H, m, PheCHO2-
H), 6.19 +1H, brd, J8.0, Phe2-NH), 6.38 +1H, brd, J8.0,
Arg2-NH), 6.67 +2H, br, Arg-HN-C+NH)-NHMbs), 7.00
+2H, d, J9.0, Mbs-arom-H), 7.18±7.31 +10H, m, Phe-
arom, PheCHO-arom-H), 7.43 +1H, brd, J9.0, Val2-NH),
7.82 +2H, d, J9.0, Mbs-arom-H), 7.80 +1H, br, Arg-HN-
C+NH)-NHMbs), 7.86 +1H, br, PheCHO2-NH), 9.58 +1H,
br, PheCHO1-H). 13C-NMR +100.6MHz, DMSO-d6) d:
18.10, 19.70 +each q, Val3-CH3£2), 26.44 +t, Arg C-4),
28.13 +q, C+CH3)3), 29.80 +d, Val C-3), 30.20 +t, Arg
C-3), 34.89 +t, Phe C-3), 39.08 +t, PheCHO C-3), 41.01
+t, Arg C-5), 54.39 +d, Arg C-2), 55.81+d, Phe C-2),
55.87 +q, Mbs-OCH3), 59.23 +d, Val C-2), 60.80 +d,
PheCHO C-2), 81.73 +s, C+CH3)3), 114.50 +d, Mbs-arom