3068
M. Adamczyk et al. / Tetrahedron: Asymmetry 11 (2000) 3063±3068
removed on a rotary evaporator. The crude product was puri®ed twice by silica gel column
chromatography (30±40% EtOAc in hexane) to aord 0.923 g of pyrrole derivative (S)-(^)-8 in
23
D
MeOH); analytical RP HPLC: MeCN:0.1% aq. tri¯uoroacetic acid, 60:40, 2.0 mL/min at 215
58% yield as a white glassy material. Rf: 0.17 (30% EtOAc in hexanes); ꢁ ^86.3 (c 1.18,
1
nm, Rt: 3.49 min, 96%; H NMR (CDCl3): ꢀ 8.23 (br s, 1H), 6.77±6.74 (m, 2H), 5.05 (dd, 1H,
J=10.2, 5.1 Hz), 3.82 (s, 3H), 3.74 (s, 3H), 3.28 (dd, 1H, J=14.7, 5.1 Hz), 3.80 (dd, 1H, J=14.7,
10.2 Hz), 1.43 (s, 18H); 13C NMR (CDCl3): ꢀ 170.9, 161.5, 151.8, 122.3, 122.1, 121.2, 115.9, 83.0,
59.0, 52.2, 51.3, 27.8, 27.4; ESI-MS (m/z): 427 (M+H)+, 444 (M+NH4)+, 870 (M+NH4)+; HRMS
(FAB, m/z) calcd for C20H30N2O8: 426.2002 (M)+; observed: 426.2008.
3.7. (S)-(^)-3-(2-Carboxy-4-pyrrolyl)-alanine (CPA) 1
Tri¯uoroacetic acid (10 mL) was added to the pyrrole derivative (S)-(^)-8 (0.548 g, 1.29 mmol)
in CH2Cl2 (10 mL) at room temperature and stirred for 30 min. The mixture was concentrated on
a rotary evaporator and the residual tri¯uoroacetic acid was removed azeotropically using
toluene (5Â10 mL). The resulting crude amine was dried on a vacuum pump (1.0 mm/Hg) for 20
min and dissolved in THF (30 mL). To this mixture, LiOH (monohydrate, 1.08 g, 25.8 mmol,
20.0 equiv.) and water (45 mL) were added at room temperature and the mixture was stirred for
1.5 h. Progress of the reaction was monitored by analytical RP HPLC (MeCN:0.1% aq.
tri¯uoroacetic acid, 4:96, 2.0 mL/min at 215 nm). An additional amount of LiOH (monohydrate,
0.271 g, 6.45 mmol, 5.0 equiv.) was added to the reaction mixture and the stirring was continued
at room temperature. After 1.5 h, pH of the mixture was adjusted to about 7.0 using 0.1% aq.
tri¯uoroacetic acid and concentrated on a rotary evaporator. The residue (1.16 g) was dissolved
in a mixture of MeCN:0.1% aq. tri¯uoroacetic acid (40 mL, 4:96 ratio) and puri®ed by
preparative RP HPLC (MeCN:0.1% aq. tri¯uoroacetic acid, 4:96, 40 mL/min at 215 nm). The
product was concentrated on a rotary evaporator to about 100 mL volume and lyophilized to
aord 0.235 g of (S)-(^)-CPA (1) as its TFA salt in 59% yield (white/pale pink powder).
Analytical RP HPLC: MeCN:0.1% aq. tri¯uoroacetic acid, 6:94, 2.0 mL/min at 215 nm, Rt: 2.80
23
min, >99%; ꢁ ^2.98 (c 1.14, 1.0 M aq. NaOH); CD spectra: (23ꢀC; c 0.00011 g/mL H2O)
D
1
[ꢂ]215 +2835 L cm^1 mol^1; H NMR (DMSO-d6): ꢀ 8.16 (brs, 3H), 6.83 (d, 1H, J=1.5 Hz), 6.63
(d, 1H, J=1.5 Hz), 4.14±4.06 (m, 1H), 3.41 (br s, 2H), 2.95 (d, 2H, J=5.4 Hz); 13C NMR
(DMSO-d6): ꢀ 170.6, 161.8, 123.1, 116.4, 115.3, 52.9, 27.4; ESI-MS (m/z): 199 (M+H)+, 397
(2ÂM+H)+; HRMS (FAB, m/z) calcd for C8H10N2O4: 199.0719 (M+H)+; observed: 199.0719.
References
1. Konno, K.; Hashimoto, K.; Ohfune, Y.; Shirahama, H.; Matsumoto, T. J. Am. Chem. Soc. 1988, 110, 4807±4815.
2. For a recent review on kainoid amino acid chemistry, see: Parsons, A. F. Tetrahedron 1996, 52, 4149±4174.
3. (a) Yamano, K.; Konno, K.; Shirahama, H. Chemistry Lett. 1991, 1541±1542. (b) Yamano, K.; Shirahama, H.
Tetrahedron 1992, 48, 1457±1464.
4. (a) Adamczyk, M.; Reddy, R. E. Tetrahedron Lett. 1996, 37, 2325±2326. (b) Adamczyk, M.; Fishpaugh, J. R.;
Heuser, K. J.; Ramp, J. M.; Reddy, R. E.; Wong, M. Tetrahedron 1998, 54, 3093±3112. (c) Adamczyk, M.;
Johnson, D. D.; Reddy, R. E. Angew. Chem., Int. Ed. Engl. 1999, 38, 3537±3539. (d) Adamczyk, M.; Johnson,
D. D.; Reddy, R. E. Bioorg. Med. Chem. Lett. 2000, 10, 269±271.
5. Sutherland A.; Caplan, J. F.; Vederas, J. C. Chem. Commun. 1999, 555±556.
6. Adamczyk, M.; Johnson, D. D.; Reddy, R. E. Tetrahedron: Asymmetry 1999, 10, 775±781.
7. Barton, D. H. R.; Kervagoret, J.; Zard, S. Z. Tetrahedron 1990, 46, 7587±7598.