Preparation of N-Fmoc-N-methyl-a-amino acids and N-nosyl-N-methyl-a-amino acids
N-Nosyl-L-isoleucine benzhydryl ester (3e)
135
(CH3)2CH) ppm. 13C-NMR (75 MHz, CDCl3) d 168.9,
149.8, 145.3, 138.9, 128.8, 128.5, 128.4, 128.3, 128.2,
127.0, 126.9, 124.3, 77.9, 65.2, 30.3, 28.2, 19.3 ppm. GC/
MS (EI) m/z (%) 271 (100), 186 (20), 167 (62), 122 (35).
Anal. calcd for C25H26N2O6S: C, 62.23; H, 5.43; N, 5.81;
O, 19.89; S, 6.64. Found: C, 62.15; H, 5.42; N, 5.79.
Yellow solid, Mp 92–94°C. Rf = 0.46 (solvent system A),
0.51 (solvent system B). 1H-NMR (300 MHz, CDCl3)
d 7.85 (d, J = 9.2 Hz, 2 H, o-NO2), 7.75 (d, J = 9.2 Hz,
2 H, m-NO2), 7.21–7.40 (m, 10 H, RCO2CH(C6H5)2), 6.58
(s, 1 H, RCO2CHPh2), 5.60 (s, J = 9.3 Hz, 1 H, NH), 3.98
(d, J = 8.3 Hz, 1 H, a-CH), 1.90 (m, 1 H, CH(CH3)
CH2CH3), 1.50 (m, 1 H, –CH(CH3)CH2CH3), 1.22 (m, 1 H,
CH(CH3)CH2CH3), 0.94 (d, J = 4.8 Hz, 3 H, –CH(CH3)
CH2CH3), 0.81 (t, J = 7.3 Hz, 3 H, CH(CH3)CH2CH3)
ppm. GC/MS (EI) m/z (%) 271 (60), 186 (28), 167 (100),
122 (21). Anal. calcd for C25H26N2O6S: C, 62.18; H, 5.43;
N, 5.81; O, 19.89; S, 6.64. Found: C, 62.23; H, 5.41; N,
5.82.
N-Methyl-N-nosyl-D-valine benzhydryl ester (4b)
Yellow solid, Mp 95–97°C. Rf = 0.50 (solvent system
A), 0.64 (solvent system B). H-NMR (300 MHz, CDCl3)
1
d 7.92 (d, J = 8.4 Hz, 2 H, o-NO2), 7.75 (d, J = 8.4 Hz,
2 H, m-NO2), 7.14–7.35 (m, 10 H, RCO2CH(C6H5)2),
6.67 (s, 1 H, RCO2CHPh2), 4.39 (d, J = 10.5 Hz, 1 H,
a-CH), 2.94 (s, 3 H, NCH3), 2.21 (m, 1 H, (CH3)2CH),
1.03 (d, J = 6.3 Hz, 3 H, (CH3)2CH), 0.85 (d, J = 6.3 Hz,
3 H, (CH3)2CH) ppm. 13C-NMR (75 MHz, CDCl3)
d 168.9, 149.8, 145.3, 138.9, 128.8, 128.5, 128.4, 128.3,
128.2, 127.0, 126.9, 124.3, 77.9, 65.2, 30.3, 28.2, 19.3
ppm. GC/MS (EI) m/z (%) 271 (100), 186 (20), 167 (62),
122 (35). Anal. calcd for C25H26N2O6S: C, 62.23; H, 5.43;
N, 5.81; O, 19.89; S, 6.64. Found: C, 62.41; H, 5.44; N,
5.79.
N-Nosyl-L-alanine benzhydryl ester (3f)
Yellow solid, Mp 100–102°C. Rf = 0.26 (solvent system
A), 0.34 (solvent system B). H-NMR (300 MHz, CDCl3)
1
d 8.04 (d, J = 9.2 Hz, 2 H, o-NO2), 7.88 (d, J = 9.2 Hz,
2 H, m-NO2), 7.19–7.38 (m, 10 H, RCO2CH(C6H5)2),
6.64 (s, 1 H, RCO2CHPh2), 5.76 (d, J = 9.1 Hz, 1 H,
NH), 4.23 (m, 1 H, a-CH), 1.48 (d, J = 6.0 Hz, 3 H,
CH3) ppm. GC/MS (EI) m/z (%) 229 (44), 186 (18), 167
(100), 122 (15). Anal. calcd for C22H20N2O6S: C, 59.99;
H, 4.58; N, 6.36; O, 21.79; S, 7.28. Found C, 59.99;
H, 4.59; N, 6.34.
N-Methyl-N-nosyl-L-leucine benzhydryl ester (4c)
Yellow solid, Mp 93–95°C. Rf = 0.57 (solvent system A),
0.58 (solvent system B). H-NMR (300 MHz, CDCl3) d
1
7.95 (d, J = 9.0 Hz, 2 H, o-NO2), 7.75 (d, J = 9.0 Hz, 2
H, m-NO2), 7.18–7.38 (m, 10 H, RCO2CH(C6H5)2), 6.60
(s, 1 H, RCO2CHPh2), 4.84 (m, 1 H, a-CH), 2.90 (s, 3 H,
N-Methyl-N-nosyl-a-amino acid benzhydryl esters
4a–f: general procedure
NCH3), 1.69–1.78 (m,
3
H, (CH3)2CHCH2 and
A 0.66 M solution of diazomethane in dry dichloromethane
(8 mmol) was cautiously added dropwise to a magnetically
stirred solution of the N-nosyl-a-amino acid benzhydryl
esters 3a–f (1 mmol) in dry dichloromethane (10 mL). The
resulting mixture was stirred at room temperature. TLC
analysis (solvent system A: EtOAc:hexane = 1:5; solvent
system B: Et2O:petroleum ether = 1:1) showed the com-
plete conversion of the precursors 3a–f after 1.5 h.
Evaporation of the solvent under reduced pressure afforded
the N-methyl-N-nosyl-a-amino acid benzhydryl esters 4a–f
in quantitative yields.
(CH3)2CHCH2), 1.03 (d, J = 6.0 Hz, 3 H, (CH3)2CHCH2),
0.99 (d, J = 6.0 Hz, 3 H, (CH3)2CHCH2) ppm. 13C-NMR
(75 MHz, CDCl3) d 169.8, 144.3, 139.1, 130.0, 128.6,
128.5, 126.7, 124.0, 78.0, 57.7, 38.2, 30.0, 24.5, 23.0,
21.0 ppm. GC/MS (EI) m/z (%) 285 (100), 186 (22), 167
(42), 122 (15). Anal. calcd for C26H28N2O6S: C, 62.89; H,
5.68; N, 5.64; O, 19.33; S, 6.46. Found: C, 63.01; H, 5.69;
N, 5.63.
N-Methyl-N-nosyl-S-benzyl-L-cysteine benzhydryl ester
(4d)
N-Methyl-N-nosyl-L-valine benzhydryl ester (4a)
Amorphous yellow solid. Rf = 0.62 (solvent system A),
0.63 (solvent system B). 1H-NMR (300 MHz, CDCl3)
d 8.06 (d, J = 9.1 Hz, 2 H, o-NO2), 7.88 (d, J = 9.1 Hz,
2 H, m-NO2), 7.18–7.42 (m, 15 H, RCO2CH(C6H5)2 and
SCH2C6H5), 6.70 (s, 1 H, RCO2CHPh2), 4.90 (m, 1 H,
a-CH), 3.76–3.82 (m, 2 H, SCH2Ph), 2.98 (m, 1 H,
CH2SBzl), 2.81 (s, 3 H, NCH3), 2.65 (m, 1 H, CH2SBzl)
ppm. 13C-NMR (75 MHz, CDCl3) d 168.1, 149.8, 139.1,
138.9, 137.3, 128.5, 128.4, 128.3, 128.0, 126.7, 124.1,
Yellow solid, Mp 91–93°C. Rf = 0.50 (solvent system A),
0.64 (solvent system B). 1H-NMR (300 MHz, CDCl3)
d 7.95 (d, J = 8.4 Hz, 2 H, o-NO2), 7.78 (d, J = 8.4 Hz,
2 H, m-NO2), 7.16–7.38 (m, 10 H, RCO2CH(C6H5)2), 6.62
(s, 1 H, RCO2CHPh2), 4.35 (d, J = 10.5 Hz, 1 H, a-CH),
2.92 (s, 3 H, NCH3), 2.18 (m, 1 H, (CH3)2CH), 1.05
(d, J = 6.3 Hz, 3 H, (CH3)2CH), 0.88 (d, J = 6.3 Hz, 3 H,
123