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E. Caballero et al. / Tetrahedron: Asymmetry 9 (1998) 967–981
reduced pressure. The residue was chromatographed on silica gel, eluting with ethyl acetate, yielding
2.125 g (60%) of compound 3a.
Method B: To a solution of the suitable tryptophan methyl ester (2 g, 9.17 mmol) in dry
dichloromethane (50 ml) was added the suitable isomer of Boc-alanine (1.73 g, 9.17 mmol) and
EDC (1.76 g, 9.17 mmol). The reaction was protected from light and stirred at room temperature for
24 h. The solution was washed with 1 N aqueous HCl (10 ml) and 1 N aqueous NaHCO3 (10 ml).
The residue was chromatographed on silica gel, eluting with ethyl acetate.25 The yields obtained were:
compound 3a, 3.14 g (88%); compound 3b, 3.26 g (91%); compound 4a, 3.25 g (91%); compound 4b,
3.22 g (90%).
Data for 3a: mp, 121–122°C. IR (KBr): 3320.3 (NH); 1740.1 (CO2CH3); 1698.6, 1662.7 (CO–N)
cm−1; 1H-NMR (CDCl3) δ: 8.16 (br. s, 1H, NHi); 7.52 (d, 1H, J=7.6 Hz, H-40); 7.35 (d, 1H, J=8.0 Hz,
H-70); 7.15 (m, 2H, H-50,60); 7.03 (s, 1H, H-20); 6.54 (d, 1H, J=7.5 Hz, NH); 5.06 (br. s, 1H, NH); 4.91
(m, 1H, Hα-Ala); 4.13 (m, 1H, Hα-Trp); 3.67 (s, 3H, CO2CH3); 3.33 (d, 2H, J=5.0 Hz, Hβ-Trp); 1.41 (s,
9H, Boc); 1.30 (d, 3H, J=6.6 Hz, CH3-Ala). 13C-NMR (CDCl3) δ: 172.50, 172.21 (CO-Ala, CO2CH3);
155.20 (CO2C(CH3)3); 136.20 (C-70a); 127.66 (C-30a); 123.18 (C-20); 122.25 (C-40); 119.66 (C-50);
118.60 (C-60); 111.46 (C-70); 109.73 (C-30); 81.00 (CO2C(CH3)3); 53.04 (Cα-Trp); 52.50 (CO2CH3);
50.26 (Cα-Ala); 28.36 (CO2C(CH3)3); 27.65 (Cβ-Trp); 18.51 (CH3-Ala) ppm. [α]D25=+32.4 (0.50,
CHCl3). Anal. calcd for C20H27N3O3: C, 61.68; H, 6.99; N, 10.79. Found: C, 61.30; H, 6.95; N, 10.60.
Data for 3b: mp, 123–124°C. [α]D25=−32.9 (0.50, CHCl3). Anal. calcd for C20H27N3O3: C, 61.68;
H, 6.99; N, 10.79. Found: C, 61.41; H, 6.94; N, 10.29. Spectral data were identical to those of compound
3a.
Data for 4a: mp, 125–126°C. IR (KBr): 3320.4 (NH), 1734.1 (CO2CH3); 1699.8, 1669.5 (CO–N)
1
cm−1. H-NMR (CDCl3) δ: 8.72 (br. s, 1H, NHi); 7.50 (d, 1H, J=7.6 Hz, H-40); 7.31 (d, 1H, J=7.7
Hz, H-70); 7.14 (m, 2H, H-50,60); 6.96 (d, 1H, J=2.3 Hz, H-20); 5.27 (d, 1H, J=7.2 Hz, NH); 4.88 (m,
1H, Hα-Ala); 4.14 (m, 1H, Hα-Trp); 3.59 (s, 3H, CO2CH3); 3.28 (d, 2H, J=4.8 Hz, Hβ-Trp); 1.41 (s,
9H, Boc); 1.24 (d, 3H, J=6.7 Hz, CH3-Ala). 13C-NMR (CDCl3) δ: 172.37 (CO-Ala, CO2CH3); 155.20
(CO2C(CH3)3); 136.21 (C-70a); 127.52 (C-30a); 123.13 (C-20); 122.26 (C-40); 119.67 (C-50); 118.55
(C-60); 111.39 (C-70); 109.74 (C-30); 81.00 (CO2C(CH3)3); 52.60 (Cα-Trp); 52.51 (CO2CH3); 50.20
(Cα-Ala); 28.38 (CO2C(CH3)3); 27.70 (Cβ-Trp); 18.44 (CH3-Ala) ppm. [α]D25=+55.6 (0.50, CHCl3).
Anal. calcd for C20H27N3O3: C, 61.68; H, 6.99; N, 10.79. Found: C, 61.22; H, 6.90; N, 10.79.
Data for 4b: mp, 125–126°C. [α]D25=−55.8 (0.50, CHCl3). Anal. calcd for C20H27N3O3: C, 61.68;
H, 6.99; N, 10.79. Found: C, 62.18; H, 7.14; N, 10.42. Spectral data were identical to those of compound
4a.
3.2. (S,S)-Methyl N-(benzyloxycarbonyl)alanyltryptophanate 8
To a solution of (S)-tryptophan methyl ester 1a (0.894 g, 4.0 mmol) in dry THF (37 ml) was added
(S)-Boc-alanine (0.892 g, 4.0 mmol) and DCC (0.825 g, 4.0 mmol). The solution was refluxed for 90
min. The precipitate of dicyclohexylurea was filtered off, and the filtrate was evaporated under reduced
pressure. The residue was recrystallized from chloroform–hexane, yielding 1.109 g (64%) of compound
1
8. Mp, 120°C. IR (KBr): 3300 (NH); 1725 (CO2CH3); 1685, 1640 (CO–N) cm−1. H-NMR (CDCl3)
δ: 8.07 (br. s, 1H, NHi); 7.54 (d, 1H, J=7.6 Hz, H-40); 7.48 (m, 6H, H-70 and CH2–C6H5); 7.13 (m,
2H, H-50,60); 6.94 (s, 1H, H-20); 6.53 (d, 1H, J=7.4 Hz, NH); 5.27 (d, 1H, J=7.4 Hz, NH); 5.04 (AB
system, 2H, CH2–C6H5); 4.90 (m, 1H, Hα-Ala); 4.22 (m, 1H, Hα-Trp); 3.67 (s, 3H, CO2CH3); 3.30
(d, 2H, J=5.3 Hz, Hβ-Trp); 1.31 (d, 3H, J=6.9 Hz, CH3-Ala). 13C-NMR (CDCl3) δ: 172.19 (CO-Ala,
CO2CH3); 155.20 (CO2CH2C6H5); 136.16 (C-70a); 128.67, 128.16 and 128.32 (CO2CH2C6H5); 127.57