K. V a´ vrov a´ et al. / Bioorg. Med. Chem. 11 (2003) 5381–5390
5387
General procedure for the preparation of the N-acyl-
amino acid esters
N-Octanoylglycine octyl ester (8G8). C H NO ;
18 35 3
À1
313.48 g mol . Yield: 70%; white crystals; mp=55.5–
3428, 3331, 2923, 2851, 1740,
max
ꢀ
1641, 1548, 1473, 1463, 1243, 729, 720 cm ; H NMR
56 C; IR (KBr): n
À1
1
3
.3 mmol of TEA was added to a suspension of 3 mmol
of amino acid ester hydrochloride in ca. 20 mL of
chloroform and stirred for 1 h. The mixture was washed
several times with brine, the organic layer was dried
with Na SO and evaporated to dryness. The resulting
oil (glycine or l-serine ester) was kept overnight in
vacuo over sulphuric acid to remove the residual TEA.
The amino acid ester and 3 mmol of N-acyloxy-
succinimide were dissolved in 25 mL of drychloroform
and stirred at room temperature. The reaction was
monitored byTLC (chloroform/methanol 9:1). After
(300 MHz, CDCl ): d 5.97 (1H; bs; NH); 4.14 (2H; t;
3
J=6.7 Hz; COO–CH2); 4.03 (2H; d; J=5.2 Hz;
CH NH); 2.23 (2H; t; J=7.7 Hz; COCH ); 1.75–1.55
2
2
(4H; m; 2CH ); 1.40–1.15 (18H; m; 9CH ); 0.95–0.75
2
2
4
2
1
3
(6H; m; 2 CH3); C NMR (75 MHz, CDCl ): d 173.2;
3
170.2; 65.7; 41.3; 36.4; 31.7; 31.6; 29.2; 29.1; 29.0; 28.5;
25.8; 25.6; 22.6; 22.6; 14.1; CHN analysis (% calculated/
found): C 68.97/68.69; H 11.25/11.51; N 4.47/4.42
N-Oleoylglycine dodecyl ester (12G18). C H NO ;
3
2
61
3
À1
2
5
0 h, the reaction mixture was washed with water and
% HCl. The organic layer was dried by Na SO and
507.83 g mol . The reaction was carried out in di-
chloromethane and the product was obtained bycol-
umn chromatographyusing silicagel and dieth yl ether
as the eluent followed bycr ys tallisation from petroleum
ether. Yield: 78%; white crystals; mp=53.5–54.5 C; IR
(KBr): nmax 3428, 3313, 3006, 2918, 2850, 1740, 1646,
2
4
evaporated. Pure products were crystallised from
chloroform: diethyl ether.
ꢀ
N-Dodecanoylglycine dodecyl ester (12G12). The data
3
À1
1
were reported earlier.
1551, 1469, 1214, 719 cm
;
H NMR (300 MHz,
CDCl ): d 5.95 (1H; bs; NH); 5.40–5.20 (2H; m;
3
N-Undecanoylglycine
undecyl
À1
ester
C H NO ; 397.63 g mol . Yield: 90%; white crys-
(11G11).
CH¼CH); 4.12 (2H; t; J=6.7 Hz; COO–CH ); 4.01
2
(2H; d; J=4.7 Hz; CH NH); 2.21 (2H; t; J=7.6 Hz;
2
2
4
47
3
ꢀ
tals; mp=76.5–77.5 C; IR (KBr): n
3421, 3333,
919, 2850, 1740, 1642, 1547, 1473, 1463, 1245, 730,
719 cm ; H NMR (300 MHz, CDCl ): d 5.97 (1H; bs;
NH); 4.14 (2H; t; J=6.9 Hz; COO–CH ); 4.03 (2H; d;
COCH ); 2.05–1.85 (4H; m; 2 CH CH¼); 1.70–1.50
max
2
2
2
(4H; m; 2CH ); 1.45–1.10 (38H; m; 19 CH ); 0.95–0.75
2 2
À1
1
13
(6H; m; 2CH3); C NMR (75 MHz, CDCl ): d 173.2;
3
3
170.2; 130.0; 129.7; 65.7; 41.3; 36.4; 31.9; 29.7; 29.7;
29.6; 29.6; 29.5; 29.5; 29.5; 29.5; 29.3; 29.2; 29.2; 29.1;
28.5; 27.2; 27.1; 25.8; 25.6; 22.7; 14.1; CHN analysis (%
calculated/found): C 75.68/75.16; H 12.11/12.45; N
2.76/2.33.
2
J=4.6 Hz; CH NH); 2.23 (2H; t; J=7.7 Hz; COCH );
2
2
1
0
.75–1.50 (4H; m; 2 CH ); 1.40–1.15 (30H; m; 15CH );
2 2
.87 (6H; t; J=6.6 Hz; 2CH3); C NMR (75 MHz,
1
3
CDCl ): d 173.2; 170.2; 65.7; 41.3; 36.4; 31.9; 29.6; 29.5;
3
2
9.5; 29.4; 29.3; 29.2; 28.5; 25.8; 25.6; 22.7; 14.1; CHN
analysis (% calculated/found): C 72.49/72.16; H 11.91/
2.15; N 3.52/3.33
N-Dodecanoyl-L-serine
dodecyl
À1
ester
(12S12).
C H NO ; 455.72 g mol . Yield: 55%; white crys-
1
2
7
53
4
ꢀ
ꢀ
25 C
D
ꢀ
tals; mp=85–86 C; ½ꢀꢁ
=12.5 (1.0; chloroform); IR
3436, 3315, 2919, 2850, 1734, 1649, 1548,
max
N-Decanoylglycine decyl ester (10G10). C H NO ;
2
(KBr): n
1467, 1282, 1242, 1082, 721 cm ; H NMR (300 MHz,
2
43
3
À1
À1
1
3
7
1
69.58 g mol . Yield: 76% white crystals; mp=70.5–
3428, 3332, 2919, 2850, 1740,
ꢀ
641, 1548, 1473, 1464, 1243, 729, 719 cm ; H NMR
2 C; IR (KBr): n
CDCl ): d 6.51 (1H; d; J=7.1 Hz; NH); 4.70–4.60 (1H;
max
3
À1
1
m; CHNH); 4.16 (2H; t; J=6.7 Hz; COO–CH ); 3.94
(2H; d; J=3.6 Hz; CH OH); 2.96 (1H; bs; OH); 2.26
2
(
300 MHz, CDCl ): d 5.98 (1H; bs; NH); 4.14 (2H; t;
3
2
J=6.7 Hz; COO–CH2); 4.03 (2H; d; J=5.0 Hz;
CH NH); 2.23 (2H; t; J=7.7 Hz; COCH ); 1.75–1.50
(2H; t; J=7.7 Hz; COCH ); 1.75–1.55 (4H; m; 2 CH );
2
2
1.40–1.10 (34H; m; 17 CH ); 0.87 (6H; t; J=6.6 Hz;
2
2
2
1
3
(
(
4H; m; 2CH ); 1.40–1.10 (26H; m; 13CH ); 0.95–0.75
2
2CH3); C NMR (75 MHz, CDCl ): d 173.9; 170.6;
2
3
1
3
6H; m; 2CH3); C NMR (75 MHz, CDCl ): d 173.2;
66.1; 63.8; 54.8; 36.5; 31.9; 29.6; 29.5; 29.5; 29.5; 29.3;
29.2; 29.2; 28.4; 25.8; 25.6; 22.7; 14.1; CHN analysis (%
calculated/found): C 75.92/76.16; H 12.55/13.02; N
2.60/2.70.
3
1
2
70.2; 65.7; 41.3; 36.4; 31.9; 29.6; 29.5; 29.5; 29.4; 29.3;
9.2; 28.5; 25.8; 25.6; 22.7; 14.1; CHN analysis (% cal-
culated/found): C 71.50/71.40; H 11.73/11.89; N 3.79/
.62
3
N-Oleoyl-L-serine dodecyl ester (12S18). C H NO ;
63
3
3
4
À1
N-Nonanoylglycine nonyl ester (9G9). C H NO ;
2
537.86 g mol . The same procedure as for the prepara-
tion of N-oleoylglycine dodecyl ester. Yield: 75%; white
=11.0 (1.0; chloro-
form); IR (KBr): n 3478, 3308, 3007, 2921, 2851,
max
1718, 1651, 1546, 1465, 1281, 1085, 721 cm ; H NMR
0
39
3
À1
3
6
1
41.53 g mol . Yield: 84%; white crystals; mp=61.5–
ꢀ
ꢀ
ꢀ
25 C
D
ꢀ
3 C; IR (KBr): n
642, 1547, 1473, 1463, 1245, 730, 719 cm ; H NMR
3421, 3333, 2919, 2850, 1740,
À1
crystals; mp=71.5–72 C; ½ꢀꢁ
max
1
À1
1
(
300 MHz, CDCl ): d 5.98 (1H; bs; NH); 4.14 (2H; t;
3
J=6.7 Hz; COO–CH2); 4.03 (2H; d; J=4.9 Hz;
CH NH); 2.23 (2H; t; J=7.6 Hz; COCH ); 1.80–1.55
(300 MHz, CDCl ): d 6.46 (1H; bs NH); 5.40–5.20 (2H;
3
m; CH¼CH); 4.70–4.60 (1H; m; CHNH); 4.15 (2H; t;
2
2
(
(
4H; m; 2CH ); 1.45–1.15 (22H; m; 11CH ); 0.95–0.80
2 2
J=6.3 Hz; COO–CH ); 4.00–3.85 (2H; m; CH OH);
2
2
1
3
6H; m; 2CH3); C NMR (75 MHz, CDCl ): d 173.2;
2.62 (1H; bs OH); 2.25 (2H; t; J=7.4 Hz; COCH2);
2.10–1.90 (4H; m; 2 CH CH¼); 1.75–1.50 (4H; m; 2
3
1
2
70.2; 65.7; 41.3; 36.4; 31.9; 29.6; 29.5; 29.5; 29.4; 29.3;
9.2; 28.5; 25.8; 25.6; 22.7; 14.1; CHN analysis (% cal-
2
CH ); 1.40–1.00 (38H; m; 19 CH ); 0.95–0.80 (6H; m; 2
2
2
1
3
culated/found): C 70.33/70.09; H 11.51/11.74; N 4.10/
.96
CH3); C NMR (75 MHz, CDCl ): d 173.8; 170.6;
3
3
130.0; 129.7; 66.1; 63.9; 54.9; 36.5; 31.9; 29.7; 29.7; 29.6;