(S)-2-(4-Mercapto-2-methyl-1H-imidazol-1-yl)-4-methyl
(1H, br s), 9.70 (1H, br s); dC(75 MHz; CDCl3) 37.3, 41.9, 52.7,
pentanoic acid 12a
54.7; 63.6, 127.9, 129.6, 130.1, 137.7, 164.8, 170.8, 171.3, 204.2;
[a]D -95.1 (c 1 in CH2Cl2); m/z (DCI) 338 (100%), 304, 265, 90,
76.
20
Hydrolysis was carried out by stirring a solution of compound 11b
(86 mg, 0.26 mmol) in 1.5 M HCl in H2O:dioxane 1:1 at 40 ◦C
overnight. After concentration in vacuo, the residue was taken up
in water and freeze-dried. 56 mg (100%) of compound 12b were
obtained as a pale yellow foam.
(S)-Methyl 2-(2-(4-(tert-butoxycarbonylthio)-1H-imidazol-1-yl)-
3-phenylpropanamido)acetate 15a
dH(300 MHz; DMSO) 0.85 (3H, d, J 6.6), 0.88 (3H, d, J 6.6),
1.17–1.20 (1H, m), 1.81–2.02 (2H, m), 2.40 (3H, s), 4.62 (1H, dd, J
9.8, 6.0), 7.20 (1H, s); dC(75 MHz; DMSO) 11.6, 21.3, 22.6, 24.3,
58.0, 126.2, 148.3, 170.0.
Thioamide resulting from treatment of 14 (250 mg, 0.74 mmol)
was dehydrated to give the S-Boc mercaptoimidazole 15a (131mg,
42%), using the procedure described for 2c.
(Found: C, 57.69; H, 5.76; N, 9.89; S, 7.75. C20H25N3O5S requires
C, 57.26; H, 6.01; N, 10.02; S, 7.64); dH(300 MHz; CDCl3), two
rotamers, ratio 9:1, major: 1.48 (9H,s), 3.17 (1H, dd, J 14.0, 9.4),
3.50 (1H, dd, J 14.0, 5.7), 3.71 (3H, s), 3.99 (2H, t, J 5.5), 4.81 (1H,
dd, J 9.2, 5.8), 6.99–7.02 (2H, m), 7.16–7.22 (3H, m), 7.29 (1H,
s), 7.32 (1H, d, J 1.1); dC(75 MHz; CDCl3) 28.3, 39.3, 41.5, 52.5,
62.9, 85.8, 124.7, 127.4, 127.7, 128.9, 129.0, 135.8, 138.5, 154.8,
(S)-2-(4-Mercapto-1H-imidazol-1-yl)-4-methyl pentanoic acid 12b
Hydrolysis was carried out by stirring a solution of compound 11b
(86 mg, 0.26 mmol) in 1.5 M HCl in H2O:dioxane 1:1 at 40 ◦C
overnight. After concentration in vacuo, the residue was taken up
in water and freeze-dried. 56 mg (100%) of compound 12b were
obtained as a pale yellow foam.
20
168.4, 169.7; [a]D -55.3 (c 0.85 in CH2Cl2); m/z (DCI) 420, 376,
320, 222, 79.
dH(300 MHz; D2O) 0.76 (3H, d, J 6.6), 0.78 (3H, d, J 6.6),
1.38–1.47 (1H, m), 1.88–2.05 (2H, m), 5.15 (1H, dd, J 10.4, 5.5),
7.51 (1H, d, J 1.3), 8.79 (1H, s); dC(75 MHz; D2O) 20.5, 22.2, 24.7,
(S)-Methyl 2-(2-(4-(methylthio)-1H-imidazol-1-yl)-3-phenyl
propanamido)acetate 15b
20
39.0, 62.1, 125.5, 127.7, 138.8, 141.4, 147.5, 172.9. [a]D +72.6 (c
1.22 in EtOH).
The procedure for the formation of 2c was used, except that methyl
iodide (2 molar equiv) was used instead of Boc2O.
(S)-Methyl 2-(2-(cyanomethylamino)-3-phenyl propanamido)
acetate 13
dH(300 MHz; CDCl3): 2.35 (3H, s), 3.17 (1H, dd, J 14.1, 9.6),
3.51 (1H, dd, J 14.1, 5.7), 3.70 (3H, s), 4.00 (2H, d, J 5.4), 4.90
(1H, dd, J 9.4, 5.5), 6.97–7.00 (2H, m), 7.06 (1H, s), 7.19–7.21
(3H, m), 7.26 (1H, s), 7.88 (1H, t, J 5.4); dC(75 MHz; CDCl3)
18.1, 39.1, 41.3, 52.4, 62.5, 118.3, 127.3, 128.7, 128.8, 135.9, 136.1,
The dipeptide Phe-Gly-OMe was treated as described for 8.
(Found: C, 60.57; H, 6.17; N, 15.86. C14H17N3O3 requires C,
61.08; H, 6.22; N, 15.26); dH(300 MHz; DMSO + TFA) 3.11 (2H,
d, J 6.6), 3.63 (3H, s), 3.92 (2H, d, J 5.6), 4.17 (2H, s), 7.24–
7.31 (5H, m), 7.40 (1H, dd, J 6.4, 3.0), 7.87 (1H, dd, J 6.2, 3.0),
9.11 (1H, t, J 5.6); dC(75 MHz; DMSO + TFA) 36.2, 41.0, 52.1,
20
137.6, 168.9, 169.9; m/z (ESI) 334; [a]D -54.5 (c 0.22 in CH2Cl2).
(S)-2-(2-(4-Mercapto-1H-imidazol-1-yl)-3-phenyl
propanamido)acetic acid 16a
20
60.7, 125.6, 128.8, 129.8, 134.3, 167.4, 169.9; [a]D -28.9 (c 0.94
in EtOH).
The procedure used for compound 7 was applied.
dH(300 MHz; D2O) 3.32 (1H, dd, J 13.9, 10.0), 3.54 (1H, dd,
J 13.9, 5.9), 3.93 (1H, d, J 17.9), 4.02 (1H, d, J 17.9), 5.38 (1H,
dd, J 9.0, 6.0), 7.14–7.17 (2H, m), 7.29–7.31 (3H, m), 7.44 (1H,
s), 8.65 (1H, s); dC(75 MHz; CDCl3) 38.4, 41.5, 63.7, 127.9, 128.0,
(S)-Methyl 2-(2-(N-(cyanomethyl)formamido)-3-phenyl
propanamido)acetate 14
Aminonitrile 13 was treated with HCOOH/Ac2O, using the same
protocol than for 9b.
20
129.0, 129.2, 129.3, 134.9, 138.5, 169.6, 173.0; [a]D -96.9 (c 0.8
(Found: C, 59.62; H 5.14; N 13.68. C15H17N3O4 requires C,
59.40; H, 5.65; N, 13.85); dH(300 MHz; DMSO + TFA) 3.01 (1H,
dd, J 14.3, 10.1), 3.21 (1H, dd, J 14.3, 5.5), 3.61 (3H, s), 3.89 (1H,
d, J 5.9), 4.19 (1H, d, J 17.5), 4.34 (1H, d, J 17.5), 4.64–4.69 (1H,
m), 7.18–7.27 (5H, m), 7.92 (1H, s), 8.79 (1H, t, J 5.7); 13C NMR
(CDCl3, 75 MHz) 29.8, 36.2, 41.4, 52.7, 62.6, 115.3, 127.7, 129.1,
in CH2Cl2); m/z (ESI) 304.
(S)-Methyl 4-(tert-butoxycarbonylamino)-4-(1-methyl-4-
(methylthio)-1H-imidazol-2-yl)butanoate 17
Following the procedure described for the formation of 15b,
thioamide 5 (444 mg, 1.28 mmol) led to protected mercaptoim-
idazole 17 (198 mg, 45%).
20
129.3, 135.5, 168.6, 168.9, 170.0; [a]D -62.6 (c 1 in CH2Cl2).
dH(300 MHz; CDCl3): 1.43 (9H, s), 2.16–2.38 (2H, m), 2.39 (3H,
s), 2.71 (2H, t, J 7.4), 3.51 (3H, s), 3.72 (3H, s), 4.35 (1H, m), 5.77
(1H, br d, J 7.0), 6.77 (1H, s); dC(75 MHz; CDCl3) 19.0, 23.3, 28.7,
29.9, 32.9, 52.7, 53.9, 80.1, 121.9, 133.2, 148.3, 156.0, 173.1.
(S)-Methyl 2-(2-(N-(2-amino-2-thioxoethyl)formamido)-3-
phenylpropanamido)acetate
Obtained by treatment of the aminonitrile 14 with thioacetic acid
(see procedure for 1).
(Found: C, 53.42; H 5.82; N 12.32, S 9.43. C15H19N3O4S requires
C, 53.40; H, 5.68; N, 12.45; S, 9.50); dH(300 MHz; DMSO + TFA)
two rotamers, ratio 3:1, major: 3.05–3.26 (2H, m), 3.60 (3H, s), 3.84
(2H, d, J 5.7), 4.00 (1H, d, J 17.5), 4.09 (1H, d, J 17.5), 4.54 (1H,
t, J 7.7), 7.19–7.30 (5H, m), 8.07 (1H, s), 8.77 (1H, t, J 5.6), 8.87
(S)-Methyl 4-(tert-butoxycarbonylamino)-4-(1-methyl-1H-
imidazol-2-yl)butanoate 18
Refluxing sulfide 17 (99 mg, 0.29 mmol) in ethanol (15 cm3), in
the presence of 50 mg of Raney nickel (50% in water) during
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