131
9. Cool the solution to 0 °C with an ice bath and form Trt-His
NCA.HCl as a precipitate which is isolated as the only product
after filtration.
10. Transfer the NCA salt to another flask of 500 mL and dry
overnight under HV (12.5 g = 28 mmol).
11. Subsequently, distill 200 mL of EtAc into the flask; remove
the flask from HV, fill with Ar, and place to an ice bath.
12. Add slowly dropwise under vigorous stirring (duration of
additional 1 h), at 0 °C, 3.5 mL (28 mmol) of the stoichiometric amount of triethylamine dissolved in 50 mL of the
same solvent.
13. Filter off the resulted triethylamine hydrochloride and pour
the filtrate into 1.5 L of non-solvent hexane in order to recrystallize the Trt-His-NCA.
14. Make a second recrystallization with a mixture of solvent/
non-solvent EtAc/hexane (1:5) and isolate by filtration the
white solid precipitate Trt-His-NCA.
15. Finally, dry Trt-HIS-NCA under HV overnight and transfer it
into glove box resulting in 11.05 g (27 mmol, 67% yield).
1. Suspend γ-benzyl-l-glutamate in dry ethyl acetate followed by
addition of triphosgene.
2. Heat the mixture at 70 °C until the solution becomes clear,
indicating the formation of the NCA.
3. Distill off the solvent in the vacuum line, and distill fresh dry
ethyl acetate in the flask, to dissolve the crude NCA, followed
by removal of the solvent by distillation.
4. Repeat twice this procedure in order to remove the excess
phosgene that sublimes under high vacuum.
5. Remove the unreacted species, such as free amino acids along
with the HCl salts of the amino acids produced during the
synthesis, by extraction with an alkali solution in water.
6. Purify further the resulted BLG-NCA by three recrystallizations from dry ethyl acetate/hexane (1/5 v/v) under high
vacuum at −20 °C, leading to a 65% yield of the BLG-NCA
formation.
1. Add in a flame-dried 1 L two-neck round-bottom flask 15 g
(114 mmol) of l-leucine and degas under high vacuum
overnight.
3.2.3 Synthesis
of γ-Benzyl-l-Glutamate
N-Carboxy Anhydride
(BLG-NCA)
3.2.4 Synthesis
of l-Leucine N-Carboxy
Anhydride (LEU-NCA)
Nanostructured Hydrogels for Controlled Drug Delivery
9. Cool the solution to 0 °C with an ice bath and form Trt-His
NCA.HCl as a precipitate which is isolated as the only product
after filtration.
10. Transfer the NCA salt to another flask of 500 mL and dry
overnight under HV (12.5 g = 28 mmol).
11. Subsequently, distill 200 mL of EtAc into the flask; remove
the flask from HV, fill with Ar, and place to an ice bath.
12. Add slowly dropwise under vigorous stirring (duration of
additional 1 h), at 0 °C, 3.5 mL (28 mmol) of the stoichiometric amount of triethylamine dissolved in 50 mL of the
same solvent.
13. Filter off the resulted triethylamine hydrochloride and pour
the filtrate into 1.5 L of non-solvent hexane in order to recrystallize the Trt-His-NCA.
14. Make a second recrystallization with a mixture of solvent/
non-solvent EtAc/hexane (1:5) and isolate by filtration the
white solid precipitate Trt-His-NCA.
15. Finally, dry Trt-HIS-NCA under HV overnight and transfer it
into glove box resulting in 11.05 g (27 mmol, 67% yield).
1. Suspend γ-benzyl-l-glutamate in dry ethyl acetate followed by
addition of triphosgene.
2. Heat the mixture at 70 °C until the solution becomes clear,
indicating the formation of the NCA.
3. Distill off the solvent in the vacuum line, and distill fresh dry
ethyl acetate in the flask, to dissolve the crude NCA, followed
by removal of the solvent by distillation.
4. Repeat twice this procedure in order to remove the excess
phosgene that sublimes under high vacuum.
5. Remove the unreacted species, such as free amino acids along
with the HCl salts of the amino acids produced during the
synthesis, by extraction with an alkali solution in water.
6. Purify further the resulted BLG-NCA by three recrystallizations from dry ethyl acetate/hexane (1/5 v/v) under high
vacuum at −20 °C, leading to a 65% yield of the BLG-NCA
formation.
1. Add in a flame-dried 1 L two-neck round-bottom flask 15 g
(114 mmol) of l-leucine and degas under high vacuum
overnight.
3.2.3 Synthesis
of γ-Benzyl-l-Glutamate
N-Carboxy Anhydride
(BLG-NCA)
3.2.4 Synthesis
of l-Leucine N-Carboxy
Anhydride (LEU-NCA)
Nanostructured Hydrogels for Controlled Drug Delivery