反应详情

Boc-Gly-Gly-Gly-OH (382 mg, 1.34 mmol) and N,N,N′,N′-Tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (532 mg, 1.4 mmol) were dissolved in DMF (5 mL). N,N-Diisopropylethylamine (488 uL, 2.8 mmol) was added and the mixture was allowed to stir at room temperature for 10-15 minutes. Afterwards, a solution of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (833 mg, 1.12 mmol) in chloroform (5 mL) was added and the reaction vessel was flushed with argon. After 16 hours at room temperature, the reaction mixture was concentrated and partitioned between dichloromethane (50 mL) and H2O (50 mL), extracted with dichloromethane (3×50 mL), dried with sodium sulfate, filtered and concentrated. Material was purified via silica gel chromatography using a dichloromethane/methanol gradient to yield colorless oil residue. To this, 2 M HCl/Diethyl Ether (5 mL) was added and the reaction mixture was allowed to stir in a H2O bath for approximately 2 hours. The reaction mixture was concentrated and the residue was taken up in dichloromethane (75 mL), washed with saturated sodium bicarbonate solution (75 mL), extracted product with dichloromethane (3×75 mL), dried with sodium sulfate, filtered and concentrated to yield (Z)-(2R)-3-(2-(2-(2-(2-aminoacetamido)acetamido)acetamido)ethoxy)(hydroxy)phosphoryl)oxy)propane-1,2-diyl dioleate as a semi-solid (765 mg, 90%). Verified by NMR.

1. customthe reaction vessel was flushed with argon
2. waitAfter 16 hours at room temperature
3. concentrationthe reaction mixture was concentrated
4. custompartitioned between dichloromethane (50 mL) and H2O (50 mL)
5. extractionextracted with dichloromethane (3×50 mL)
6. dry with materialdried with sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customMaterial was purified via silica gel chromatography
10. customto yield colorless oil residue
11. stirringto stir in a H2O bath for approximately 2 hours
12. concentrationThe reaction mixture was concentrated
13. washwashed with saturated sodium bicarbonate solution (75 mL)
14. extractionextracted product with dichloromethane (3×75 mL)
15. dry with materialdried with sodium sulfate
16. filtrationfiltered
17. concentrationconcentrated