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CAS No. : | 89889-51-0 | MDL No. : | MFCD06796002 |
Formula : | C22H38N4O5S | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | SRKRKWYAHKIBEW-FIKGOQFSSA-N |
M.W : | 470.63 | Pubchem ID : | 22851428 |
Synonyms : |
|
Chemical Name : | 6-(6-(5-((3aS,4S,6aR)-2-Oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamido)hexanamido)hexanoic acid |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
25% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dimethyl sulfoxide; N,N-dimethyl-formamide; at 20℃; | To a solution of d-biotin-Acp-Acp-OH (54 mg, 0.114 mmol) in DMF/DMSO (5 mL) were added HOBt·H2O (16 mg, 0.114 mmol), EDC·HCl (22 mg, 0.114 mmol), and 3-azido propylamine (23 mg, 0.228 mol), and the mixture was stirred at room temperature overnight. The resultant precipitates were collected and washed with EtOAc. The precipitate was then purified by preparative HPLC (with a linear gradient of 10-60% CH3CN in 0.1% aq TFA over 40 min) to give a white powder of compound 20 (16 mg, 25%). 1H NMR (600 MHz, DMSO-d6) δ 1.18-1.38 (m, 10H), 1.42-1.54 (m, 7H), 1.58-1.65 (m, 3H), 2.00-2.04 (m, 6H), 2.57 (d, 1H, J = 12 Hz), 2.82 (dd, 1H, J = 5.0, 12 Hz), 2.99 (q, 4H, J = 6.0 Hz), 3.07-3.11 (m, 3H), 3.32-3.37 (m, 2H, overlapping with H2O), 4.11-4.13 (m, 1H), 4.30 (dd, 1H, J = 5.0, 7.7 Hz), 6.36 (s, 1H), 6.42 (s, 1H), 7.71 (t, 1H, J = 5.0 Hz), 7.74 (t, 1H, J = 5.0 Hz), 7.83 (t, 1H, J = 5.0 Hz); HRMS (ESI): m/z 553.3287 (M+H+) (calcd for C25H45N8O4S: 553.3284). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
13.4%; 14% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; for 24h; | General procedure: A solution of glaucocalyxin A (332 mg, 1.0 mmol, 1.0 equiv) in DMF (20 ml) was added biotin (293 mg, 1.2 mmol, 1.2 equiv) and 1-ethyl-3(3-dimethylpropylamine)carbodiimide (EDCI, 383 mg, 2.0 mmol, 2.0 equiv) and DMAP (122 mg, 1.0 mmol, 1.0equiv) at room temperature. The reaction mixture was stirred at room temperature for 24 h. The reaction mixture was then diluted with water and extracted with ethyl acetate. The extract was washed with saturated NaCl (aqueous) solution, dried over anhydrous Na2SO4, filtered, and evaporated to give a white solid residue. The crude residue was purified by silica gel column, eluted with EtOAc/MeOH (12:1, v/v) to afford a mixture. Then the crude residue was further purified by preparative reversed phase liquid chromatography, elution with MeOH-H2O (70:30, v/v) at 3 ml/min to afford the desired compounds 5 and 6. Compounds 7, 8, 9, 10, 11, 12, 13a, 14a,13 b, 14 b,13c and 14c were obtained according to the similar procedure of preparing 5 and 6 starting from 1, 2, 3, 4a, 4b and 4c. GLA-biotin derivatives were all white solids. Compound 5, 280 mg, yield 50.2%. Compound 6, 101 mg, yield 18.1%.Compound 7, 251 mg, yield 18.0%. Compound 8, 121 mg, yield 37.4%. Compound 9,110 mg, yield 13.4%. Compound 10, 105 mg, yield 14.0%. Compound 11, 94 mg, yield 13.9%. Compound 12, 30 mg, yield 4.4%. Compound 13a, 102 mg, yield 15.1%. Compound 14a, 65 mg, yield 9.6%. Compound 13 b, 169 mg, yield 21.0%. Compound 14 b, 45 mg, yield 6.5%. Compound 13c, 96 mg, yield 13.8%. Compound 14c, 64 mg,yield 9.2%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72.2% | With triethylamine; In N,N-dimethyl-formamide; | General procedure: A solution of Biotin (488 mg, 2.0 mmol, 1.0 equiv) in N, N-dimethylformamide(DMF, 20 ml) was added N-hydroxysuccinimide (NHS, 276 mg, 2.4 mmol, 1.2 equiv) and dicyclohexylcarbodiimide (DCC, 824 mg, 4.0 mmol, 2.0 equiv) and 4-dimethylaminopyridine(DMAP, 610 mg, 5.0 mmol, 2.5 equiv) at room temperature. The solution was stirred overnight, and then the solvent was removed under reduced pressure. The residue was dissolved in isopropanol (40 ml) with ultrasonic. The solution was cool to 4 C and stood for 1 h. The resulted mixture was filtered to afford intermediate a. Intermediate a (341 mg, 1.0 mmol, 1.0 equiv) and 6-aminocaproic acid(157 mg, 1.2 mmol, 1.2 equiv) were dissolved in 20 ml DMF. Triethylamine (0.3 ml,2.16 mmol, 2.16 equiv) was added. The solution was stirred overnight, and then the solvent was removed under reduced pressure. The residue was dissolved in water(25 ml) and formic acid (2 ml) with ultrasonic. The solution was cooled to 4 C. The resulted mixture was filtered to afford compound 1. Intermediate b was obtained according to the similar procedure of preparing intermediate a staring from 1. Compound 2 was obtained according to the similar procedure of preparing compound 1 staring from intermediate b. To a solution of biotin (400 mg, 2.0 mmol, 1.0equiv) and tributylamine (0.64 ml, 2.7 mmol, 1.3 equiv) in DMF (40 ml) was added isobutyl chloroformate (0.32 ml, 2.5 mmol, 1.2 equiv) at room temperature. The reaction mixture was stirred 10 min, and then 3-aminobenzoic acid (548 mg, 4.0 mmol,2.0 equiv) in 40 ml DMF was added slowly to the mixture at 0 C and left to stir for 2 h. The solvent was removed under reduced pressure. The residue was dissolved inwarm ethanol solution (50%, 36 ml). The pH of the mixture was adjusted to 2.0 by hydrochloric acid. The mixture was cooled to 0 C and stood for 12 h. The resulted mixture was filtered to give compound 3. Compounds 4a, 4 b and 4c were obtained according to the similar procedure of preparing 3 starting from 4-aminobenzoic acid, 4-amino-3-methylbenzoic acid and 4-amino-3-fluorobenzoic acid. The biotin derivatives were all white solids. Compound 1, 270 mg, yield 75.6%. Compound 2, 340 mg,yield 72.2%. Compound 3, 465 mg, yield 62.4%. Compound 4a, 483 mg, yield 64.9%. Compound 4b, 600 mg, yield 77.6%. Compound 4c, 465 mg, yield 62.4%. |