4-(Cholest-5-en-3beta-yloxy)butanoic acid → [4-(Cholest-5-en-3beta-yloxy)butanoyl]-15-amino-4,7,10,13-tetraoxapentadecanol
Reaction equation
[CH3:1][CH:2]([CH2:4][CH2:5][CH2:6][C@H:7]([C@@H:9]1[C@:26]2([CH3:27])[C@H:12]([C@H:13]3[C@H:23]([CH2:24][CH2:25]2)[C@:21]2([CH3:22])[C:16]([CH2:17][C@@H:18]([O:28][CH2:29][CH2:30][CH2:31][C:32]([OH:34])=O)[CH2:19][CH2:20]2)=[CH:15][CH2:14]3)[CH2:11][CH2:10]1)[CH3:8])[CH3:3].[NH2:35][CH2:36][CH2:37][O:38][CH2:39][CH2:40][O:41][CH2:42][CH2:43][O:44][CH2:45][CH2:46][O:47][CH2:48][CH2:49][C:50](O)=[O:51]>>[CH3:3][CH:2]([CH2:4][CH2:5][CH2:6][C@H:7]([C@@H:9]1[C@:26]2([CH3:27])[C@H:12]([C@H:13]3[C@H:23]([CH2:24][CH2:25]2)[C@:21]2([CH3:22])[C:16]([CH2:17][C@@H:18]([O:28][CH2:29][CH2:30][CH2:31][C:32]([CH:50]([OH:51])[CH2:49][CH2:48][O:47][CH2:46][CH2:45][O:44][CH2:43][CH2:42][O:41][CH2:40][CH2:39][O:38][CH2:37][CH2:36][NH2:35])=[O:34])[CH2:19][CH2:20]2)=[CH:15][CH2:14]3)[CH2:11][CH2:10]1)[CH3:8])[CH3:1]Participants
3
Procedure
The mixture of pentafluorophenyl ester of 4-(Cholest-5-en-3β-yloxy)butanoic acid (121 mg, 0.19 mmol) and 15-amino-4,7,10,13-tetraoxapentadecanoic acid (104 mg, 0.39 mmol) was dried in an apparatus equipped with septum for 4 h at room temperature and 0.1 Pa. The apparatus was flushed with argon (2×) and then dry N,N-dimethylformamide (4 ml) and N-ethyldiisopropylamine (1 ml) were added through the septum and the mixture was stirred at room temperature for 16 h. Flash chromatography of the crude reaction mixture on silica gel column (100 ml) in toluene-ethyl acetate (gradient: 0-40% ethyl acetate, 10 ml/min, 160 min) gave [4-(Cholest-5-en-3β-yloxy)butanoyl]-15-amino-4,7,10,13-tetraoxapentadecanol acid (general formula X, where n3=3 and n4=3; 208 mg, 88%). 1H NMR (400 MHz, Acetone) δ ppm: 3.71 t, J=6.32 Hz, 2H (CH2-3); 3.55-3.60 m, 14H (7×CH2—O); 3.51 t, J=5.60 Hz, 2H (CH2-14); 3.45 t, J=6.32 Hz, 2H (CH2-4′); 3.34 q, J=5.73 Hz, 1H (CH-3″); 2.53 t, J=6.32 Hz, 2H (CH2-2); 2.34 ddd, J=13.20, 4.70, 2.10 Hz, 1H (H-4a″); 2.24 t, J=7.45 Hz, 2H (CH2-2′); 1.82-2.17 m, 5H (cholesteryl); 1.76-1.82 m, 2H (CH2-3′); 1.01 s, 3H (CH3-19″); 0.94 d, J=6.57 Hz, 3H (CH3-21″); 0.87 d, J=1.26 Hz, 3H (CH3-26″); 0.86 d, J=1.52 Hz, 3H (CH3-27″); 0.81-1.66 m, 34H (cholesteryl); 0.71 s, 3H (CH3-18″); for C42H73NO8—H HR-MS, calculated m/z: 720.5409. found m/z: 720.5407.