P. M. T. Ferreira, L. S. Monteiro, G. Pereira
FULL PAPER
124.0–125.0 °C (ethyl acetate/diethyl ether). 1H NMR (CDCl3): δ
= 3.78 (s, 3 H, CH3 CO2Me), 5.07 (dd, J = 3.0, J = 8.7 Hz, 1 H,
Bz(4-NO2)-Z-∆Abu-OMe (2b): The general procedure described
above was followed with compound 1b as substrate to give 2b
αCH), 5.40 (d, J = 3.0 Hz, 1 H, βCH), 6.92 (d, J = 8.7 Hz, 1 H, (0.375 g, 71%) as a white solid. M.p. 122.5–123.0 °C (ethyl acetate/
αNH), 7.27–7.72 (m, 10 H, ArH) ppm. 13C NMR (CDCl3): δ =
52.63 (OCH3), 58.53 (αC), 73.53 (βC), 125.69 (CH), 127.04 (CH),
n-hexane). 1H NMR (CDCl3): δ = 1.88 (d, J = 7.2 Hz, 3 H, γCH3),
3.82 (s, 3 H, CH3 CO2Me), 6.97 (q, J = 7.2 Hz, 1 H, βCH), 7.62
128.00 (CH), 128.35 (CH), 128.44 (CH), 131.72 (C), 133.51 (C), (br. s, 1 H, NH), 8.04 (d, J = 9.0 Hz, 2 H, ArH), 8.34 (d, J =
139.66 (C), 167.71 (C=O), 170.95 (C=O) ppm. C17H17NO4
(299.30): calcd. C 68.22, H 5.72, N 4.68; found C 68.22, H 5.73, N
4.73.
9.0 Hz, 2 H, ArH) ppm. 13C NMR (CDCl3): δ = 15.04 (γCH3),
52.59 (OCH3), 123.84 (CH), 125.60 (αC), 128.61 (CH), 134.85
(βCH), 139.38 (C), 149.80 (C), 163.45 (C=O), 164.86 (C=O) ppm.
C12H12N2O5 (264.24): calcd. C 54.55, H 4.58, N 10.60; found C
54.52, H 4.43, N 10.57.
Bz(4-NO2)-D,L-Phe(β-OH)-OMe (5b): The general procedure de-
scribed above was followed with HCl·H-,-Phe(β-OH)-OMe and
4-nitrobenzoyl chloride to give compound 5b (0.671 g, 39%) as a
white solid. M.p. 153.0–155.0 °C (ethyl acetate/diethyl ether). 1H
NMR (DMSO): δ = 3.60 (s, 3 H, CH3 CO2Me), 4.85 (br. s, 1 H,
αCH), 5.22 (br. s, 1 H, βCH), 5.94 (d, J = 6.0 Hz, 1 H, OH), 7.18–
7.42 [m, 5 H, ArH Phe(β-OH)], 7.96 [d, J = 8.7 Hz, 2 H, ArH
Bz(NO2)], 8.27 [d, J = 8.7 Hz, 2 H, ArH Bz(NO2)], 8.95 (d, J =
8.7 Hz, 1 H, NH) ppm. 13C NMR (CDCl3): δ = 52.96 (OCH3),
58.43 (αC), 73.45 (βC), 123.80 (CH), 125.55 (CH), 128.24 (CH),
128.43 (CH), 128.61 (C), 139.26 (C), 149.68 (C), 165.51 (C=O),
170.53 (C=O) ppm. C17H16N2O6 (344.33): calcd. C 59.30, H 4.68,
N 8.14; found C 59.04, H 4.80, N 8.03.
Bz(4-OMe)-Z-∆Abu-OMe (2c): The general procedure described
above was followed with compound 1c (3 mmol, 0.804 g) as sub-
strate to give 2c (0.409 g, 82%) as a white solid. M.p. 112.0–
113.0 °C (diethyl ether/petroleum ether). 1H NMR (400 MHz,
CDCl3): δ = 1.82 (d, J = 5.4 Hz, 3 H, γCH3), 3.77 (s, 3 H, CH3),
3.85 (s, 3 H, CH3), 6.85 (q, J = 5.4 Hz, 1 H, βCH), 6.93 (d, J =
6.6 Hz, 2 H, ArH), 7.58 (br. s, 1 H, NH), 7.83 (d, J = 6.6 Hz, 2 H,
ArH) ppm. 13C NMR (CDCl3): δ = 14.87 (γCH3), 52.32 (OCH3),
55.36 (OCH3), 113.77 (CH), 126.07 (C), 126.20 (C), 129.27 (CH),
133.40 (CH), 162.51 (CO), 164.96 (C), 165.22 (CO) ppm.
C13H15NO4 (249.26): calcd. C 62.64, H 6.07, N 5.62; found C
62.05, H 6.00, N 5.63.
2-Fur-D,L-Phe(β-OH)-OMe (5e): The general procedure described
1-Naph-Z-∆Abu-OMe (2d): The general procedure described above
was followed with compound 1d as substrate to give 2d (0.473 g,
88%) as a white solid. M.p. 139.5–140.5 °C (ethyl acetate/n-hex-
ane). 1H NMR (CDCl3): δ = 1.97 (d, J = 6.9 Hz, 3 H, γCH3), 3.83
(s, 3 H, CH3 CO2Me), 6.98 (q, J = 6.9 Hz, 1 H, βCH), 7.40 (br. s,
1 H, NH), 7.47–7.62 (m, 4 H, ArH), 7.79 (d, J = 6.9 Hz, 1 H, ArH),
7.88–7.98 (m, 2 H, ArH), 8.44 (d, J = 7.8 Hz, 1 H, ArH) ppm. 13C
NMR (CDCl3): δ = 15.11 (γCH3), 52.44 (OCH3), 124.62 (CH),
125.36 (CH), 125.62 (CH), 126.01 (βCH), 126.51 (CH), 127.35
(CH), 128.34 (CH), 130.22 (C), 131.25 (CH), 133.50 (C), 133.72
(C), 134.40 (αC), 165.02 (C=O), 167.30 (C=O) ppm. C16H15NO3
(269.30): calcd. C 71.36, H 5.61, N 5.20; found C 71.13, H 5.44, N
5.33.
above was followed with HCl·H-,-Phe(β-OH)-OMe and 2-fu-
ranoyl chloride to give compound 5e (1.24 g, 86%) as a white solid.
M.p. 126.0–127.0 °C (ethyl acetate/n-hexane). 1H NMR (CDCl3): δ
= 3.33 (br. s, 1 H, OH), 3.73 (s, 3 H, CH3 CO2Me), 4.98 (dd, J =
9.0, 3.0 Hz, 1 H, αCH), 5.34 (d, J = 3.0 Hz, 1 H, βCH), 6.43–6.45
(m, 1 H, ArH), 7.00 (d, J = 3.6 Hz, 1 H, ArH), 7.18 (d, J = 9.0 Hz,
1 H, NH), 7.24–7.42 (m, 6 H, ArH) ppm. 13C NMR (CDCl3): δ =
52.62 (OCH3), 57.82 (βCH), 73.43 (αCH), 112.06 (CH), 115.00
(CH), 125.74 (CH), 128.02 (CH), 128.35 (CH), 139.60 (C), 144.33
(CH), 147.00 (C), 158.38 (C=O), 170.72 (C=O) ppm. C15H15NO5
(289.28): calcd. C 62.28, H 5.23, N 4.84; found C 62.23, H 5.25, N
4.90.
General Procedure for the Synthesis of N-Acyldehydroamino Acid
Methyl Esters: DMAP (0.1 equiv.) was added to a solution of the
N-acylamino acid methyl ester (2 mmol) in dry acetonitrile (1 ),
followed by di-tert-butyl dicarbonate (1.0 equiv.) with rapid stirring
at room temperature. The reaction was monitored by TLC (diethyl
ether/n-hexane, 1:1) until all the reactant had been consumed.
TMG (2% in volume) was then added, stirring was continued, and
the reaction was followed by TLC. When all the reactant had been
consumed, evaporation at reduced pressure gave a residue that was
partitioned between diethyl ether (100 mL) and KHSO4 (1 ,
30 mL). The organic phase was thoroughly washed with KHSO4
(1 ), NaHCO3 (1 ) and saturated brine (2ϫ30 mL) and dried
with MgSO4. Removal of the solvent afforded the corresponding
N-acyldehydroamino acid methyl ester.
2-Fur-Z-∆Abu-OMe (2e): The general procedure described above
was followed with compound 1e as substrate to give 2e (0.37 g,
88%) as a colourless oil. 1H NMR (400 MHz, CDCl3): δ = 1.84 (d,
J = 7.2 Hz, 3 H, γCH3), 3.78 (s, 3 H, CH3), 6.51–6.53 (m, 1 H,
ArH), 6.90 (q, J = 7.2 Hz, 1 H, βCH), 7.18–7.19 (m, 1 H, ArH),
7.49–7.50 (m, 1 H, ArH), 7.76 (br. s, 1 H, NH) ppm. 13C NMR
(CDCl3): δ = 14.93 (γCH3), 52.39 (OCH3), 112.33 (CH), 115.43
(CH), 125.10 (C), 134.67 (CH), 144.44 (CH), 156.00 (C=O), 164.86
(C=O) ppm.
2-Qnx-Z-∆Abu-OMe (2f): The general procedure described above
was followed with compound 1f as substrate to give 2f (0.455 g,
84%) as a light yellow solid. M.p. 106.0–107.5 °C (ethyl acetate/n-
1
hexane). H NMR (CDCl3): δ = 1.93 (d, J = 7.2 Hz, 3 H, γCH3),
3.83 (s, 3 H, CH3), 7.00 (q, J = 7.2 Hz, 1 H, βCH), 7.84–7.92 (m,
3 H, ArH), 8.15–8.22 (m, 1 H, ArH), 9.37 (br. s, 1 H, NH) 9.69 (s,
1 H, ArH) ppm. 13C NMR (CDCl3): δ = 15.04 (γCH3), 52.46
(OCH3), 125.58 (αC), 129.34 (CH), 129.76 (CH), 130.92 (CH),
131.84 (CH), 134.89 (βCH), 140.17 (C), 142.87 (C), 143.83 (CH),
143.98 (C), 161.17 (C=O), 164.75 (C=O) ppm. C14H13N3O3
(271.27): calcd. C 61.99, H 4.83, N 15.49; found C 62.17, H 4.90,
N 14.88.
Bz-∆Ala-OMe (6a) and Boc-Z-∆Abu-OMe: The synthesis of these
compounds has been described elsewhere.[10a,13]
Bz-Z-∆Abu-OMe (2a): The general procedure described above was
followed with compound 1a as substrate to give 2a (0.34 g, 83%)
as a white solid. M.p. 78.0–79.0 °C (diethyl ether/petroleum ether).
1H NMR (CDCl3): δ = 2.76 (d, J = 7.5 Hz, 3 H, γCH3), 3.77 (s, 3
H, CO2CH3), 6.88 (q, J = 7.5 Hz, 1 H, βCH), 7.41–7.55 (m, 3 H,
ArH), 7.69 (br. s, 1 H, NH), 7.85–7.88 (m, 2 H, ArH) ppm. 13C
NMR (CDCl3): δ = 14.86 (γCH3), 52.32 (OCH3), 126.07 (C),
127.35 (CH), 128.56 (CH), 131.90 (CH), 133.80 (CH), 133.83 (C),
165.06 (C=O), 165.41 (C=O) ppm. C12H13NO3 (219.24): calcd. C
65.74, H 5.98, N 6.39; found C 65.30, H 5.93, N 6.48.
Bz(4-OMe)-∆Ala-OMe (6c): The general procedure described
above was followed with compound 4c as substrate to give 6c
(0.235 g, 50%) as a white solid. M.p. 39.5–41.0 °C (ethyl acetate/n-
1
hexane). H NMR (CDCl3): δ = 3.86 (s, 3 H, CH3), 3.89 (s, 3 H,
CH3), 5.63 (d, J = 1.8 Hz, 1 H, βCH), 6.77 (s, 1 H, βCH), 6.96 (d,
4680
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Eur. J. Org. Chem. 2008, 4676–4683