The Journal of Organic Chemistry
NOTE
removed under vacuum to give a pale yellow solid (375 mg). The
product was subjected to H NMR analysis (9:1 DMSO-d6-TFA),
27.1, 28.8(8), 28.9(4), 29.1, 29.1(9), 29.2(3), 30.8, 31.5, 33.0, 33.5, 37.0,
40.9, 51.9, 52.1, 63.8, 112.9, 144.9, 170.9, 171.0, 171.1, 171.2; HRMS
(FAB) calcd for C24H44N3O6S [M þ H]þ 502.2951, found 502.2949.
Purification and purity analysis: 25.0 mg; CH3OH; 23.2 mg (93% yield);
55.2 min (1:1 H2O-CH3CN/0.1% TFA).
1
which essentially detected a single compound, S-allylglutathione hydro-
chloride: 1H NMR (9:1 DMSO-d6-TFA) δ1.95-2.09 (2H, m), 2.29-
2.42 (2H, m), 2.55 (1H, dd, J = 8.95, 13.77 Hz), 2.79 (1H, dd, J = 4.82,
13.77 Hz), 3.13 (2H, d, J = 6.89 Hz), 3.75 (2H, dd, J = 3.44, 5.51 Hz),
3.93 (1H, dd, J = 6.20, 11.71 Hz), 4.46-4.45 (1H, m), 5.03 (1H, d, J =
8.95 Hz), 5.15 (1H, d, J = 17.21 Hz), 5.68-5.75 (1H, m), 8.24-8.27
(4H, m), 8.36 (1H, t, J = 5.51 Hz); 13C NMR (9:1 DMSO-d6-TFA)
δ26.5, 31.1, 33.0, 34.4, 41.2, 52.2, 52.5, 117.6, 134.7, 171.1, 171.3, 171.4,
171.6; HRMS (FAB) calcd for C13H22N3O6S [M þ H]þ 348.1229,
found 348.1230. The yield was determined by 1H NMR analysis as follows.
To the whole crude mixture was added mesitylene (1.00 M solution in
DMSO-d6, 1.00 mL, 1.00 mmol). The solution was then subjected to 1H
NMR analysis with 10 s repetitions so that the resulting integrations of the
1H signal areas were sufficient to allow accurate quantification. The
0.980:9.00 ratio of the signal intensities of the product (δ5.70-5.79, m,
-CHdCH2) and mesitylene (δ.19, s, 3 ꢀ CH3) was used to determine
the yield as 98%. A part of the crude product (30.0 mg) was purified by a
reversed silica-gel chromatography (Wakogel 50C18 (38-63 μm particle
size; 7 mm φ ꢀ 200 mm); 9:1 H2O-CH3OH eluent) to give a pure 2b (R
= H) (28.0 mg, 93% isolated yield). The purity was confirmed by HPLC
analysis (Develosil C30-UG-5; 9:1 H2O-CH3CN containing 0.1% TFA;
0.5 mL/min flow rate; 220-nm detection; tR 48.0 min).
S-Allylated peptides were synthesized by the same procedure as that
of S-allylglutathione described above. The amount of substrate and
corresponding spectral data of the products are listed below. For the
purification and purity analysis, the same columns as those described
above were used unless otherwise specified. The loading amount, eluent,
isolated yield, and tR are reported.
S-(2-Methyl-2-propen-1-yl)glutathione. 1b (307 mg, 1.00
mmol): 1H NMR (9:1 CD3OD-TFA) δ 1.81 (3H, s), 2.15-2.30
(2H, m), 2.60 (2H, t, J = 6.89 Hz), 2.69 (1H, dd, J = 8.95, 13.77 Hz,),
2.93 (1H, dd, J = 6.89, 13.77 Hz), 3.14 (1H, d, J = 13.08 Hz), 3.19 (1H, d,
J = 13.08 Hz), 3.94 (2H, d, J = 17.21 Hz), 4.07 (1H, t, J = 6.20 Hz),
4.54-4.58 (1H, m), 4.86 (1H, s), 4.91 (1H, s); 13C NMR (9:1
CD3OD-TFA) δ 20.7, 27.1, 32.6, 33.4, 40.1, 41.9, 53.6, 54.1, 114.6,
142.4, 171.7, 171.8, 173.5, 174.6; HRMS (FAB) calcd for C14H24N3O6S
[M þ H]þ 362.1386, found 362.1390. Purification and purity analysis:
30.0 mg; 9:1 H2O-CH3OH; 27.6 mg (92% yield); 90 min (9:1 H2O-
CH3CN/0.1% TFA).
S-(2-Hexyl-2-propen-1-yl)glutathione. 1b (307 mg, 1.00
mmol). The product (420 mg) was precipitated after the reaction and
then isolated from the mixture by filtration and washing with methanol:
1H NMR (9:1 CD3OD-TFA) δ 0.90 (3H, t, J = 6.89 Hz), 1.28-1.35
(6H, m), 1.42-1.48 (2H, m), 2.15-2.20 (3H, m), 2.22-2.28 (1H, m),
2.58 (2H, t, J = 7.57 Hz), 2.68 (1H, dd, J = 8.95, 13.77 Hz), 2.92 (1H, dd,
J = 5.51, 13.77 Hz), 3.17 (1H, d, J = 13.77 Hz), 3.20 (1H, d, J = 13.77
Hz), 3.94 (2H, d, J = 15.15 Hz), 4.03 (1H, t, J = 6.20 Hz), 4.56 (1H, dd,
J = 5.51, 8.95 Hz), 4.88 (1H, s), 4.94 (1H, s); 13C NMR (9:1 CD3OD-
TFA) δ 14.4, 23.7, 27.1, 28.7, 30.1, 32.5, 32.9, 33.6, 34.8, 38.6, 41.8, 38.6,
53.6, 54.0, 113.7, 146.4, 171.5, 172.7, 173.2, 174.4; HRMS (FAB) calcd
for C19H34N3O6S [M þ H]þ 432.2168, found 432.2164. Purification
and purity analysis: 20.0 mg; CH3OH; 18.2 mg (91% yield); 9.3 min
(1:1 H2O-CH3CN/0.1% TFA).
S-(2-Undecyl-2-propen-1-yl)glutathione. 1b (307 mg, 1.00
mmol). The product (480 mg) was precipitated after the reaction and
then isolated from the mixture by filtration and washing with methanol:
1H NMR (9:1 DMSO-d6-TFA) δ 0.83 (3H, t, J = 6.89 Hz), 1.22 (16H,
brs), 1.37 (2H, brs), 1.95-2.08 (4H, m), 2.28-2.41 (2H, m), 2.49-
2.54 (1H, br), 2.74 (1H, dd, J = 4.82, 12.39 Hz), 3.10 (1H, d, J = 13.77
Hz), 3.14 (1H, d, J = 13.77 Hz), 3.75 (2H, t, J = 5.51 Hz), 3.93-3.96
(1H, m), 4.46-4.49 (1H, m), 4.81 (1H, s), 4.91 (1H, s), 8.25 (2H, brm),
8.35 (1H, brm); 13C NMR (9:1 DMSO-d6-TFA) δ 14.0, 22.3, 26.2,
S-(2-Phenyl-2-propen-1-yl)glutathione. 1b (46.1 mg, 0.150
1
mmol): H NMR (9:1 CD3OD-TFA) δ 2.11-2.26 (2H, m), 2.50-
2.58 (2H, m), 2.71 (1H, dd, J = 8.95, 14.12 Hz), 2.98 (1H, dd, J = 5.51,
13.77 Hz), 3.68 (2H, s), 3.92 (2H, s), 4.02, (1H, t, J = 6.89 Hz), 4.56
(1H, dd, J = 5.51, 8.61 Hz), 5.29 (1H, s), 5.46 (1H, d, J = 1.38 Hz), 7.26
(1H, t, J = 7.57 Hz), 7.32 (2H, t, J = 7.57 Hz), 7.47 (2H, d, J = 7.57 Hz);
13C NMR (9:1 CD3OD-TFA) δ 27.1, 32.4, 34.0, 37.4, 41.8, 53.5, 54.0,
115.9, 127.5, 128.9, 129.4, 140.6, 145.2, 171.5, 172.7, 173.2, 174.4;
HRMS (FAB) calcd for C19H26N3O6S [M þ H]þ 424.1542, found
424.1548. Purification and purity analysis: 13.2 mg; 9:1 H2O-CH3OH;
12.0 mg (91% yield); 38.5 min (8:2 H2O-CH3CN/0.1% TFA).
S-(2-Propen-1-yl)glutathione diethyl ester. 1c (32.4 mg,
1
0.100 mmol): H NMR (CD3OD) δ 1.26 (3H, t, J = 7.57 Hz), 1.34
(3H, t, J = 7.57 Hz), 2.12-2.26 (2H, m), 2.55 (2H, t, J = 6.89 Hz), 2.71
(1H, dd, J = 8.95, 13.77 Hz), 2.95 (1H, dd, J = 5.51, 14.46 Hz), 3.19 (2H,
d, J = 6.89 Hz), 3.91-3.95 (2H, m), 4.10 (1H, t, J = 6.89 Hz), 4.18 (2H,
q, J = 7.57 Hz), 4.32 (2H, t, J = 7.57 Hz), 4.53-4.57 (1H, m), 5.10 (1H,
d, J = 9.64 Hz), 5.18 (1H, d, J = 17.21 Hz), 5.76-5.84 (1H, m); 13C
NMR (CD3OD) δ 14.4, 14.5, 27.0, 32.2, 33.4, 35.6, 42.1, 53.6, 54.1, 62.3,
63.8, 117.9, 135.4, 170.2, 171.0, 173.3, 174.1; HRMS (FAB) calcd for
C17H30N3O6S [M þ H]þ 403.1850, found 403.1850. Purification and
purity analysis: 15.0 mg; 1:1 H2O-CH3OH; 13.5 mg (90% yield); 6.4
min (CH3CN/0.1% TFA).
1
Gly-Cys(S-allyl)-Gly. 1d (17.7 mg, 75.0 mmol): H NMR (9:1
CD3OD-TFA) δ 2.72 (1H, dd, J = 8.59, 13.75 Hz), 2.96 (1H, dd, J =
5.73, 13.75 Hz), 3.19 (2H, d, J = 7.45 Hz), 3.71-3.78 (2H, m), 3.96 (2H,
s), 4.60-4.64 (1H, m), 5.11 (1H, d, J = 9.16 Hz), 5.18 (1H, d, J = 17.18
Hz), 5.75-5.85 (1H, m); 13C NMR (9:1 CD3OD-TFA) δ 33.5, 35.6,
41.5, 41.8, 41.9, 54.0, 135.3, 167.3, 171.4, 172.9; HRMS (FAB) calcd for
C10H18N3O4S [M þ H]þ 276.1018, found 276.1020. Purification and
purity analysis: 10.0 mg; 9:1 H2O-CH3OH; 9.5 mg (95% yield); 7.7
min (8:2 H2O-CH3CN/0.1% TFA).
’ ASSOCIATED CONTENT
Supporting Information. 1H and 13C NMR spectra and
S
b
HPLC charts for all products. This material is available free of
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: kitamura@os.rcms.nagoya-u.ac.jp.
’ ACKNOWLEDGMENT
P.J. thanks the Council of Scientific and Industrial Research
(C.S.I.R.), New Delhi, India, and Indian Institute of Chemical
Biology (I.I.C.B.), Calcutta, India, for support through the Award
of a Raman Research Fellowship for the year 2010-11 and his
deputation to M.K.’s laboratory. We are grateful to Dr. M. Kuse
for valuable suggestions for purification of the products. This
research work was financially supported by a Grant-in-Aid for
Scientific Research (No. 25E07B212) from the Ministry of
Education, Science, Sports and Culture, Japan.
’ REFERENCES
(1) (a) For a review of the synthesis, structures, and functions of
lipidated Ras and Rab peptides and proteins, see: Brunsveld, L.;
1896
dx.doi.org/10.1021/jo102278m |J. Org. Chem. 2011, 76, 1894–1897