T. Seko et al. / Bioorg. Med. Chem. 11 (2003) 1901–1913
1911
1530, 1248 cmÀ1; MS (MALDI) m/z 486 (M+K), 470
(M+Na)+, 448 (M+H)+; 1H NMR (200 MHz,
CDCl3) d 8.77 (1H, d, J=1.8 Hz), 8.18 (1H, d,
J=7.8 Hz), 8.12 (1H, d, J=1.8 Hz), 7.25–7.18 (2H, m),
6.88–6.81 (2H, m), 4.78–4.68 (1H, m), 4.51–4.33 (2H,
m), 3.79 (3H, s), 3.16 (1H, dd, J=14.0, 5.6 Hz), 2.92
(1H, dd, J=14.0, 7.4 Hz), 2.57–2.41 (2H, m), 1.88–0.80
(11H, m). Anal. calcd for C22H29N3O3S2: C, 59.03%; H,
6.53%; N, 9.39%; S, 14.33%. Found: C, 58.87%; H,
6.49%; N, 9.34%; S, 14.20%.
(20H, m); HRMS (MALDI-TOF) calcd for
C33H45N3O5S2Na: m/z 650.2689 (M+Na)+. Found: m/
z 650.2697 (M+Na)+.
N-(N-(t-Butoxycarbonyl)-(R)-thiazolidine-4-carbonyl)-S-
cyclohexylmethyl-L-cysteine
4-phenoxybenzylamide
25
D
(21f). Amorphous solid; ½a À45.6ꢁ (c 0.61, CHCl3);
IR (KBr) n 3293, 2925, 1704, 1649, 1507, 1489, 1367,
1239; MS (FAB) m/z 614 (M+H)+, 558; 1H NMR
(300 MHz, CDCl3) d 7.36–7.23 (5H, m), 7.15–7.07 (2H,
m), 7.01–6.91 (4H, m), 4.65–4.32 (6H, m), 3.33–3.13
(3H, m), 2.79 (1H, dd, J=14.1, 6.3 Hz), 2.45–2.30 (2H,
m), 1.83–0.78 (20H, m); HRMS (MALDI-TOF) calcd
for C32H43N3O5S2Na: m/z 636.2541 (M+Na)+. Found:
m/z 636.2553 (M+Na)+.
N-(N-(t-Butoxycarbonyl)-(R)-thiazolidine-4-carbonyl)-S-
cyclohexylmethyl-L-cysteine
4-dimethylaminobenzyla-
25
D
mide (21b). Amorphous solid; ½a À39.0ꢁ (c 1.02,
CHCl3); IR (film) n 3293, 2925, 2851, 1646, 1523, 1448,
1367, 1255, 1163, 909, 804, 733 cmÀ1; MS (APCI) m/z
1
587 (M+Na)+, 565 (M+H)+, 169, 134, 117; H NMR
N-((R)-thiazolidine-4-carbonyl)-S-cyclohexylmethyl-L-cy-
steine 4-phenoxybenzylamide hydrochloride (22). Mp 75–
(200 MHz, CD3OD) d 7.20–7.10 (2H, m), 6.77–6.67
(2H, m), 4.67–4.43 (4H, m), 4.29 (1H, d, J=14.7 Hz),
4.26 (1H, d, J=14.7 Hz), 3.41–3.30 (1H, m), 3.12 (1H,
dd, J=12.1, 4.8 Hz), 3.00–2.65 (8H, m), 2.41 (2H, d,
J=6.6 Hz), 1.88–0.80 (11H, m), 1.45 (9H, s). Anal. calcd
for C28H44N4O4S2: C, 59.54%; H, 7.85%; N, 9.92%; S,
11.35%. Found: C, 59.41%; H, 7.89%; N, 9.80%; S,
11.43%.
25
D
77 ꢁC; ½a À55.0 (c 1.10, MeOH); IR (KBr) n 3239,
3039, 2923, 2850, 2706, 1656, 1589, 1547, 1507, 1489,
1447, 1356, 1238, 1166, 1105, 1070, 1015, 962, 908, 871,
846, 746, 691, 603, 499, 448, 421 cmÀ1; MS (APCI) m/z
1
514 (M+H)+; H NMR (200 MHz, CD3OD) d 7.39–
7.25 (m, 4H), 7.14–7.05 (m, 1H), 6.99–6.88 (m, 4H),
4.61–4.50 (m, 2H), 4.47–4.29 (m, 4H), 3.57 (dd, J=12.0,
7.7 Hz, 1H), 3.23 (dd, J=12.0, 7.2 Hz, 1H), 2.93 (dd,
J=13.6, 6.6 Hz, 1H), 2.80 (dd, J=13.6, 8.0 Hz, 1H),
2.53–2.36 (m, 2H), 1.90–0.80 (m, 11H). Anal. calcd for
C27H35N3O3S2.0.5H2O.HCl: C, 57.99%; H, 6.67%; N,
7.65%; S, 11.47%. Found: C, 58.10%; H, 6.50%; N,
7.65%; S, 11.53%.
N-(N-(t-Butoxycarbonyl)-(R)-thiazolidine-4-carbonyl)-S-
cyclohexylmethyl-L-cysteine 4-nitrobenzylamide (21c).
25
D
Mp: 132.2–134.5 ꢁC; ½a À27.8ꢁ (c 0.95, CHCl3); IR
(KBr) n 3289, 3055, 2923, 2850, 1695, 1690, 1674, 1656,
1604, 1519, 1449, 1366, 1345, 1258, 1165, 1111, 857,
774, 733 cmÀ1; MS (APCI) m/z 567 (M+H)+, 511, 467;
1H NMR (200 MHz, CD3OD) d 8.25–8.15 (2H, m),
7.61–7.51 (2H, m), 4.70–4.41 (6H, m), 3.45–3.32 (1H,
m), 3.22–3.08 (1H, m), 3.04–2.72 (2H, m), 2.45 (2H, d,
J=6.6 Hz), 1.91–0.80 (11H, m), 1.45 (9H, s). Anal. calcd
for C26H38N4O6S2: C, 55.10%; H, 6.76%; N, 9.89%; S,
11.32%. Found: C, 55.18%; H, 6.72%; N, 9.83%; S,
11.41%.
N-(N-Methoxycarbonyl-(R)-thiazolidine-4-carbonyl)-S-cy-
clohexylmethyl-L-cysteine 4-phenoxybenzylamide (23).
25
D
Amorphous solid; ½a À52.0ꢁ (c 1.12, CHCl3); IR
(KBr) n 3301, 3064, 2924, 2850, 1710, 1651, 1590, 1531,
1507, 1489, 1446, 1374, 1237, 1111, 1016, 962, 871, 767,
692, 499 cmÀ1; MS (MALDI) m/z 610 (M+K)+, 594
(M+Na)+, 572 (M+H)+; 1H NMR (300 MHz,
CDCl3) d 7.37–6.93 (m, 11H), 4.73–4.32 (m, 6H), 3.67
(s, 3H), 3.32 (dd, J=12.0, 3.9 Hz, 1H), 3.28 (dd,J=12.0,
6.9 Hz, 1H), 3.23–3.01 (br, 1H), 2.82 (dd, J=13.8,
6.6 Hz, 1H), 2.48–2.34 (m, 2H), 1.82–1.52 (m, 5H),
1.49–1.04 (m, 4H), 0.96–0.81 (m, 2H). Anal. calcd for
C29H37N3O5S2: C, 60.92%; H, 6.52%; N, 7.35%; S,
11.22%. Found: C, 60.56%; H, 6.45%; N, 7.30%; S,
11.62%.
N-(N-(t-Butoxycarbonyl)-(R)-thiazolidine-4-carbonyl)-S-
cyclohexylmethyl-L-cysteine
4-hydroxybenzylamide
25
D
(21d). Mp: 64.3–63.3 ꢁC; ½a À45.0ꢁ (c 0.89, CHCl3);
IR (KBr) n 3304, 2925, 2851, 1652, 1517, 1161 cmÀ1
;
(MALDI) m/z 576 (M+K)+, 560 (M+Na)+; 1H NMR
(200 MHz, CD3OD) d 7.12 (2H, d, J=8.4 Hz), 6.74–
6.68 (2H, m), 4.65–4.44 (4H, m), 4.31 (1H, d,
J=14.8 Hz), 4.23 (1H, d, J=14.8 Hz), 3.35 (1H, dd,
J=12.2, 7.4 Hz), 3.12 (1H, dd, J=12.2, 4.8 Hz), 2.99–
2.68 (2H, m), 2.41 (2H, d, J=7.0 Hz), 1.88–0.81 (20H,
m). Anal. calcd for C26H39N3O5S2 0.5H2O: C, 57.12%;
H, 7.37%; N, 7.69%; S, 11.73%. Found: C, 57.34%; H,
7.21%; N, 7.71%; S, 11.93%.
N-(N-(iso-Butoxycarbonyl)-(R)-thiazolidine-4-carbonyl)-
4-phenoxybenzylamide
S-cyclohexylmethyl-L-cysteine
25
D
(24). Mp: 76.2–77.8 ꢁC; ½a À44.7ꢁ (c 0.91, CHCl3);
IR (KBr) n 3454, 3298, 2960, 2923, 2849, 1719, 1653,
1535, 1489, 1415, 1358, 1242, 1110, 1022, 871, 764, 692,
584, 495 cmÀ1; MS (MALDI) m/z 652 (M+K)+, 636
1
N-(N-(t-Butoxycarbonyl)-(R)-thiazolidine-4-carbonyl)-S-
4-benzyloxybenzylamide
(M+Na)+; H NMR (300 MHz, CDCl3) d 7.37–6.92
cyclohexylmethyl-L-cysteine
25
(21e). Amorphous solid; ½a À47.4ꢁ (c 0.82, CHCl3);
(m, 11H), 4.73–4.29 (m, 6H), 3.84 (d, J=6.6 Hz, 2H),
3.32 (dd, J=12.3, 4.5 Hz, 1H), 3.29 (dd, J=12.3, 6.6 Hz,
1H), 3.24–3.17 (br, 1H), 2.81 (dd, J=13.5, 6.6 Hz, 1H),
2.44–2.32 (m, 2H), 1.99–1.54 (m, 6H), 1.49–1.04 (m,
4H), 0.95–0.86 (m, 8H). Anal. calcd for
C32H43N3O5S2.0.5H2O: C, 61.71%; H, 7.12%; N,
6.75%; S, 10.30%. Found: C, 61.75%; H, 6.94%; N,
6.82%; S, 10.23%.
D
IR (KBr) n 3293, 2925, 2851, 1703, 1649, 1511, 1381,
1367, 1241 cmÀ1; MS (MALDI) m/z 666 (M+K)+, 650
1
(M+Na)+; H NMR (300 MHz, CDCl3) d 7.44–7.18
(8H, m), 7.13 (1H, d, J=7.8 Hz), 6.93–6.88 (2H, m),
5.04 (2H, s), 4.65–4.21 (6H, m), 3.32–3.12 (3H, m), 2.78
(1H, dd, J=13.8, 6.3 Hz), 2.44–2.30 (2H, m), 1.80–0.78