M. Włostowski et al. / Tetrahedron Letters 51 (2010) 5977–5979
5979
23. Delson, J. L.; Hodges, H. B.; MacDouglas, D. D.; Henriksen, B. S.; Hrycyna, C. A.;
Gibbs, R. A. Bioorg. Med. Chem. Lett. 2006, 16, 4420–4423.
24. Perrey, D. A.; Uckun, F. M. Tetrahedron Lett. 2001, 42, 1859–1861.
25. Marianoff, C. A.; Leadbeater, N. E. In e-EROS Encyclopedia of Reagents for Organic
Synthesis; Crich, D.; Ed.; John Wiley & Sons, Ltd., 2007.
Method B: stoichiometric quantity of AcOH or HCl in MeOH (or EtOH) was
added to the reaction mixture and more MeOH (or EtOH) to initiate
crystallization of the product which was then recrystallized from alcohol or
diluted alcohol.
Compounds 3a–q are enantiomerically pure and were fully characterized on
26. Ishikawa, T.; Kumamoto, T. Synthesis 2006, 737–752.
the basis of spectral (1H, 13C, IR) and CHN data.
27. Ali, A.; Fahrenholtz, F.; Weinstein, B. Angew. Chem., Int. Ed. Engl. 1972, 11, 289.
28. Steglich, W.; Hinze, S. Synth. Commun. 1976, 399–401.
29. Włostowski, M.; Rowicki, T.; Synoradzki, L. Tetrahedron: Asymmetry 2004, 15,
2333–2338.
30. Luo, J.; Smith, M. D.; Lantrip, D. A.; Wang, S.; Fuchs, P. L. E. J. Am. Chem. Soc.
1997, 119, 10004–10013.
31. Kemp, D. S.; Wang, S.-W.; Rebek, J., Jr.; Mollan, R. C.; Banquer, C.;
Subramanyam, G. Tetrahedron 1974, 30, 3955–3967.
Spectral data for new compounds: compound 3k: from EtOH, mp 173–175 °C;
[
a
]
À5.6 (c 1.0, 0.1 M NaOHaq); dH (400 MHz, D2O) 3.97 (2H, dd, J = 3.2, 4.4),
D
3.28 (2H, dd, J = 14.8, 4.4), 3.15 (dd, 2H, J = 14.8, 7.6), 2.94 (4H, s); dC (100 MHz,
D2O) 173.61, 80.00, 54.04, 32.65, 19.89; mmax (KBr/cmÀ1) 3410, 3045, 1607,
1408, 1131, 541 cmÀ1
; MS (EI) silylated derivative: C22H48O4N2S2Si4, m/z
(%) = 581 (0.2) [M+], 463 (18), 317 (19), 316 (14), 315 (7), 232 (9), 220 (11), 219
(22), 218 (100), 147 (13), 73 (24). Elemental anal.: C10H16N2O4S2, calcd: C,
41.08; H, 5.52; N, 9.58; S, 21.93; obsd: C, 41.28; H, 5.41; N, 9.64; S, 22.14.
32. Williams, J. M.; Brands, K. M. J.; Skerlj, R. T.; Jobson, R. B.; Marchesini, G.;
Conrad, K. M.; Pipik, B.; Savary, K. A.; Tsay, F.-R.; Houghton, P. G.; Sidler, D. R.;
Dolling, U.-H.; DiMichele, L. M.; Nowak, T. J. J. Org. Chem. 2005, 70, 7479–7487.
33. Bera, S.; Langley, J. L.; Pathak, T. J. Org. Chem. 1998, 63, 1754–1760.
34. Włostowski, M.; Czarnocka, S.; Maciejewski, P. unpublished results.
Compound 3m: from methanol, mp 179–180 °C; [
a
]
À23.62 (c 0.1, 0.1 M
D
NaOHaq); dH (400 MHz, NaOD/D2O) 3.52 (1H, dd, J = 4.7, 7.5), 3.37 (1H, dd,
J = 5.6, 7.5), 3.05 (1H, dd, J = 4.7, 13.5), 2.84 (1H, m, J = 5.6, 13.5), 2.83 (2H, s),
2.70 (1H, dd, J = 7.5, 13.5), 1.19 (9H, s,); dC (100 MHz, NaOD/D2O) 181.57,
178.83, 70.34, 55.56, 40.08, 38.28, 30.21; mmax (KBr/cmÀ1) 3485, 3115, 2970,
35.
A
sample the mixture was concentrated, silylated with BSA [N,O-bis-
1728, 1610, 1410, 1300, 1126, 675 cmÀ1
C
;
MS (EI) silylated derivative:
(trimethysilyl)acetamide] to form the disilylated derivative and tested by
GC/MS or GC analysis on a chiral column.
15H33O4NS2Si4, m/z (%) = 379 (0.02) [M+], 234 (16), 190 (26), 146 (43), 134
(100), 116 (22), 75 (22), 73 (33), 57 (32), 43 (13); 28 (32). Elemental anal.:
C9H17NO4S, calcd: C, 45.94; H, 7.28; N, 5.95; S, 13.63; obsd: C, 46.01; H, 7.21; N,
5.98; S, 13.58.
Compound 3n: from H2O, mp 160–162 °C decomp. [
NaOHaq); dH (400 MHz, D2O) 4.01 (1H, dd, J = 6.6, 5.6), 3.60 (2H, s), 3.28 (2H,
m); dC (100 MHz, D2O) 172.82, 116,67, 53.71, 33.21, 17.35; mmax (KBr/cmÀ1
3426, 2976, 2247, 1587, 1509, 1397, 1344, 1300, 865, 546; MS (EI) silylated
derivative: C11H24N2O2SSi2, m/z (%) = 304 (0.14) [M+], 219 (20), 218 (100), 188
(14), 187 (92), 147 (35), 146 (14), 144 (34), 100 (18), 75 (14), 73 (81).
Elemental anal.: C5H8N2O2S, calcd: C, 37.49; H, 5.03; N, 17.49; S, 20.02; obsd: C,
37.52; H, 5.06; N, 17.53; S, 20.08.
36. (a) Hwang, D.-R.; Helquist, P.; Shekhani, M. S. J. Org. Chem. 1985, 50, 1264–
1271; (b) Armstrong, L.; Lewis, J. D. J. Org. Chem. 1951, 16, 749–751; (c)
Erickson, B. W.; Merrifield, R. B. J. Am. Chem. Soc. 1973, 95, 3750–3756; (d)
Berse, C.; Boucher, R.; Piche, L. J. Org. Chem. 1957, 22, 805–807; (e) Marrone, L.;
Siemann, S.; Beecroft, M.; Viswanatha, T. Bioorg. Chem. 1996, 24, 401–416; (f)
Cini, E.; Lampariello, L. R.; Rodriquez, M.; Taddei, M. Tetrahedron 2009, 65, 844–
848; (g) Joullie, M.; Lakah, L.; Maillard, G.; Muller, P. Ger. Patent 2329819,
1974; Chem. Abstr. 1974, 80, 83651.; (h) Tang, G.; Ji, T.; Hu, A.-F.; Zhao, Y.-F.
Synlett 2008, 1907–1909; (i) Moynihan, H. A.; Roberts, S. M. J. Chem. Soc., Perkin
Trans. 1 1994, 797–806; (j) Vince, R.; Daluge, S.; Wadd, W. B. J. Med. Chem.
1971, 14, 402–404.
a] 34.19 (c 0.1, 0.1 M
D
)
Compound 3o: from MeOH, mp 176–179 °C. [a]D À85.11 (c 0.1, 0.1 M NaOHaq),
37. Procedure for the synthesis of S-alkylated cysteine and related compounds 3a–q: A
solution of TMG (21 mmol) in 5 ml of MeOH (or other alcohol) was added
dH (400 MHz, NaOD/D2O) 6.89 (4H, m), 6.46 (3H, m), 3.13 (2H, s), 2.97 (1H, s),
1.16 (3H, s), 0,84 (3H, s); dC (100 MHz, NaOD/D2O) 178.71, 135.44, 133.53,
132.54, 128.58, 127.94, 127.71, 126.30, 125.90, 63.63, 51.33, 32.75, 27.71,
dropwise to a stirred (under argon) mixture of L-cysteine (10 mmol) in 10 ml of
MeOH (or other alcohol). To the homogeneous solution was added alkylation
reagent 2a–q (10 mmol) in THF dropwise and the reaction mixture was stirred
1 h at 50 °C. The mixture was evaporated and after addition of 10 ml of H2O,
acidified with a stoichiometric quantity of AcOH or HCl (1:1). The separated
precipitate was recrystallized from alcohol, dilute alcohol or H2O—Method A.
22.94; m
max (KBr/cmÀ1) 3504, 3151, 3046, 2966, 1622, 1508, 1410, 1370, 1132,
884, 836, 756, 564; MS (EI) silylated derivative: C13H28N2O2SSi2, m/z (%) = 433
(0.08) [M+], 220 (10); 219 (44), 218 (41), 215 (12), 142 (15), 141 (100), 115
(11), 73 (31), 32 (15), 28 (64). Elemental anal.: C16H19NO2S, calcd: C, 66.41; H,
6.62; N, 4.84; S, 11.08; obsd: C, 66.59; H, 6.60; N, 4.78; S, 11.01.