* 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.
2.3 Preparation of l-phenylalanine N-carboxyanhydride (NCA) (Scheme 2) A 1 L round bottom was dried in an oven prior to use (oven temp = 120 °C). The glassware was cooled under an inert nitrogen atmosphere. Phenylalanine (50.0 g, 303 mmol) was added to the flask. Anhydrous THF (600 mL, 0.5 M) was charged to give a suspension of white solid. The mixture was heated to 50 °C and triphosgene (35.9 g, 121 mmol, 0.4 equivalents) was added as a solid. The suspension was stirred until the reaction was clear (∼30 min). The reaction mixture was cooled to ambient temperature then concentrated to an oil. The oil was then slowly poured into 3 L of hexanes with rapid stirring to yield a white precipitate. The resulting suspension was capped using aluminum foil and placed in the freezer for 3 h. The white precipitate was then filtered via vacuum filtration while maintaining an inert environment. The white solid was rinsed with hexanes (3 * 20 mL) to give the product. The white solid was collected and dried overnight under vacuum. GC/MS was used to confirm the product (54.0 g, 94percent yield). 1H NMR (500 MHz, CHCl3-d): δ 7.37 - 7.30 (3 H, m); 7.18 (2 H, d, J = 7.21 Hz); 6.23 (1 H, s); 4.53 (1 H, dd, J = 8.18, 4.21 Hz); 3.27 (1 H, dd, J = 14.14, 4.20 Hz); 3.00 (1 H, dd, J = 14.13, 8.17 Hz) .
Reference：
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[2] RSC Advances, 2016, vol. 6, # 8, p. 6368 - 6377
[3] Chemical Communications, 2008, # 48, p. 6570 - 6572
[4] Chemical Communications, 2015, vol. 51, # 86, p. 15645 - 15648
[5] Bioconjugate Chemistry, 2015, vol. 26, # 4, p. 725 - 734
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[11] Biopolymers, 2017, vol. 107, # 11,
[12] Biomacromolecules, 2013, vol. 14, # 1, p. 200 - 206
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[14] Helvetica Chimica Acta, 2010, vol. 93, # 1, p. 158 - 168
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[18] Langmuir, 2013, vol. 29, # 51, p. 15981 - 15991
2
[ 75-44-5 ]
[ 63-91-2 ]
[ 14825-82-2 ]
Yield
Reaction Conditions
Operation in experiment
86%
at 50℃; for 1 h;
Phenylalanine NCA [0393] H-L-Phe-OH (20.0 g, 132 mmol) was suspended in 300 mL of anhydrous THF and heated to 50° C. Phosgene (20percent in toluene) (90 mL, 182 mmol) was added to the amino acid suspension, and the amino acid dissolved over the course of approx. 1 hr, forming a cloudy solution. The solution was filtered through a paper filter (Whatman 1), concentrated on by rotary evaporation, transferred to a beaker, and hexane was added to precipitate the product. The white solid was isolated by filtration and dissolved in anhydrous THF. The solution was filtered over a bed of Celite to remove any insoluble material. An excess of hexanes were added on the filtrate while stirring with a spatula. The NCA was isolated by filtration and dried in vacuo. 20.0 g (86percent yield) of D-PheNCA was isolated as a white, crystalline solid. 1H NMR (d6-DMSO) δ 9.09 (1H), 7.40-7.08 (5H), 4.788 (1H), 3.036 (2H) ppm.
86%
at 50℃; for 1.5 h;
H-E-Phe-OH (20.0 g, 132 mmol) was suspended in300 mE of anhydrous THF and heated to 50° C. Phosgene (20percent in toluene) (90 mE, 182 mmol) was added to the amino acid suspension, and the amino acid dissolved over the course of approx. 1 hr, forming a cloudy solution. The solution was filtered through a paper filter (Whatman 1), concentrated on by rotary evaporation, transferred to a beaker, and hexane was added to precipitate the product. The white solid was isolated by filtration and dissolved in anhydrous THF. The solution was filtered over a bed of Celite to remove any insoluble material. An excess of hexanes were added on the filtrate while stirring with a spatula. The NCA was isolated by filtration and dried invacuo. 20.0 g (86percent yield) of D-PheNCA wasisolated as a white, crystalline solid. ‘H NMR (d5-DMSO)9.09 (1H), 7.40-7.08 (5H), 4.788 (1H), 3.036 (2H) ppm.
Phenylalanine NCA [0393] H-L-Phe-OH (20.0 g, 132 mmol) was suspended in 300 mL of anhydrous THF and heated to 50° C. Phosgene (20percent in toluene) (90 mL, 182 mmol) was added to the amino acid suspension, and the amino acid dissolved over the course of approx. 1 hr, forming a cloudy solution. The solution was filtered through a paper filter (Whatman 1), concentrated on by rotary evaporation, transferred to a beaker, and hexane was added to precipitate the product. The white solid was isolated by filtration and dissolved in anhydrous THF. The solution was filtered over a bed of Celite to remove any insoluble material. An excess of hexanes were added on the filtrate while stirring with a spatula. The NCA was isolated by filtration and dried in vacuo. 20.0 g (86percent yield) of D-PheNCA was isolated as a white, crystalline solid. 1H NMR (d6-DMSO) delta 9.09 (1H), 7.40-7.08 (5H), 4.788 (1H), 3.036 (2H) ppm.
86%
In tetrahydrofuran; toluene; at 50℃; for 1.5h;
H-E-Phe-OH (20.0 g, 132 mmol) was suspended in300 mE of anhydrous THF and heated to 50° C. Phosgene (20percent in toluene) (90 mE, 182 mmol) was added to the amino acid suspension, and the amino acid dissolved over the course of approx. 1 hr, forming a cloudy solution. The solution was filtered through a paper filter (Whatman 1), concentrated on by rotary evaporation, transferred to a beaker, and hexane was added to precipitate the product. The white solid was isolated by filtration and dissolved in anhydrous THF. The solution was filtered over a bed of Celite to remove any insoluble material. An excess of hexanes were added on the filtrate while stirring with a spatula. The NCA was isolated by filtration and dried invacuo. 20.0 g (86percent yield) of D-PheNCA wasisolated as a white, crystalline solid. ?H NMR (d5-DMSO)9.09 (1H), 7.40-7.08 (5H), 4.788 (1H), 3.036 (2H) ppm.
With cyclohexene; In 1,4-dioxane; at 60 - 65℃; for 7h;
To a solution of 20g L-Phenyl alanine, 2 equivalents of cyclohexene and 150ml of 1,4-Dioxane, 2.5 equivalents of phosgene was purged at 60-65 C in one hour. After Phosgenation stirred at reflux temp for 6hours. The . contents were allowed to cool to room temperature, chilled to 10 C and precipitated the desired carboxy anhydride by the addition of hexane. The precipitated solid was filtered under inert atmosphere, dried and stored
(S)-2-{(S)-2-[(S)-2-((S)-2-{(S)-2-[(S)-2-((S)-2-Amino-3-phenyl-propionylamino)-3-phenyl-propionylamino]-3-phenyl-propionylamino}-3-phenyl-propionylamino)-3-phenyl-propionylamino]-3-phenyl-propionylamino}-3-phenyl-propionic acid[ No CAS ]
2.3 Preparation of l-phenylalanine N-carboxyanhydride (NCA) (Scheme 2) A 1 L round bottom was dried in an oven prior to use (oven temp = 120 °C). The glassware was cooled under an inert nitrogen atmosphere. Phenylalanine (50.0 g, 303 mmol) was added to the flask. Anhydrous THF (600 mL, 0.5 M) was charged to give a suspension of white solid. The mixture was heated to 50 °C and triphosgene (35.9 g, 121 mmol, 0.4 equivalents) was added as a solid. The suspension was stirred until the reaction was clear (?30 min). The reaction mixture was cooled to ambient temperature then concentrated to an oil. The oil was then slowly poured into 3 L of hexanes with rapid stirring to yield a white precipitate. The resulting suspension was capped using aluminum foil and placed in the freezer for 3 h. The white precipitate was then filtered via vacuum filtration while maintaining an inert environment. The white solid was rinsed with hexanes (3 * 20 mL) to give the product. The white solid was collected and dried overnight under vacuum. GC/MS was used to confirm the product (54.0 g, 94percent yield). 1H NMR (500 MHz, CHCl3-d): delta 7.37 - 7.30 (3 H, m); 7.18 (2 H, d, J = 7.21 Hz); 6.23 (1 H, s); 4.53 (1 H, dd, J = 8.18, 4.21 Hz); 3.27 (1 H, dd, J = 14.14, 4.20 Hz); 3.00 (1 H, dd, J = 14.13, 8.17 Hz) .
In tetrahydrofuran; at 50℃; for 4h;Inert atmosphere;
The L-Phe-NCA was synthesized from L-Phe (5.0 g) and triphosgene (3.7 g) in dry THF (50 mL) at 50 °C for 4 h under N2 atmosphere. After completion of the reaction, the mixture was concentrated by rotary evaporator at 30 °C and dry hexane was added to precipitate the crude product. The crude product was purified by recrystallization from diethyl ether/hexane (1/2, v/v) twice to yield L-Phe-NCA monomer of high purity. 1H NMR (300 MHz, CDCl3): delta 7.19?7.41 (m, 5H, ArH), 5.60 (s, 1H, NH), 4.55 (m, 1H, CH), 2.94?3.35 (m, 2H, CH2). FTIR (KBr, cm?1): nu 3351 (N?H), 3031 (C?H from phenyl), 2905 (C?H), 1849 (C=O), 1779 (C=O).
In tetrahydrofuran; at 40℃;Inert atmosphere;
General procedure: BGlu (0.020 mol) or Phe (0.026 mol) and anhydrous tetrahydrofuran (THF) were added into a dried glass reactor to form a suspension. Triphosgen (0.023 mol) was separately dissolved in fresh anhydrous THF and injected drop wise into reaction mixture. Nitrogen was bubbled through the mixture during synthesis. The mixture was heated at about 40 °C with constant stirring till mixture became transparent. The solution was precipitated in n-hexane and then stored at ? 20 °C overnight in order to allow complete precipitation of gamma-benzyl l-glutamate-N-carboxyanhydride (BGlu-NCA) or l-phenylalanine -N-carboxyanhydride (Phe-NCA). The white solids obtained were collected and purified further by repeated precipitation with n-hexane. The resulting NCA monomers were dried under vacuum for 24 h and characterized by the proton nuclear magnetic resonance (1H NMR).#10;
General procedure: A 4-necked 2 L flask is equipped with a mechanical stirrer and a condenser, which is charged with dry ice. L-valine (1 17.2 g, 1 .0 mol) is suspended in THF (1 L) and phosgene (150 g, 1 .5 mol) is added during 30 min. The temperature rises to 50 °C. The reaction mixture is stirred under reflux (approx. 60 °C) until a clear solution is obtained (after approx. 40 min). Nitrogen was purged through the solution during 1 h to remove excess of phosgene. The solvent is evaporated and the residue is dissolved in toluene (1 L). Heptane (0.6 L) is added and the suspension is stirred at 0 °C for 1 h. The precipitate is filtered off, washed twice with toluene/heptane (1 :2, 0.15 L) and dried at 60 °C in vacuum. Yield: 1 15.9 g (81 percent). 1H-NMR (600 MHz, DMSO): delta = 9.09 (s, 1 H), 4.35 (d, J = 3 Hz, 1 H), 2.08-2.03 (m, 1 H), 0.96 (d, J = 6 Hz, 3H), 0.87 (d, J = 6 Hz, 3H) ppm.
EXAMPLE 262 (S)-4-(Phenylmethyl)-2,5-oxazolidinedione A mixture of 8.9 g of L-phenylalanine, 4.8 ml of trichloromethylchloroformate (Diphosgene), 70 ml of dry tetrahydrofuran and 0.135 g of activated carbon is heated in an oil bath at 55° C. for 2 hours, until the L-phenylalanine is in solution. The reaction is filtered through diatomaceous earth. The filtrate is concentrated in vacuo, treated with diethyl ether and hexane, and the resulting crystals are collected to give 1.04 g of the desired product. 1 H NMR(CDCl3): delta7.19-7.17(m,2H); 7.38-7.31(m,3H); 6.31(s,1H,NH); 4.56-4.52(m,1H,CH); 3.30-3.29(m,1H); 3.04-2.97(m,1H).
0.27 g
General procedure: To a glass flask was added 0.52 g (4.4 mmol) of L-valine, Hydrogen sulphate Tetrabutyl amine (4mmol) of TBA-HSO4 was added to the mixture, and then 1.54g (containing 4mmol of sodium hydroxide) of 20.78wtpercent aqueous solution of sodium hydroxide was added and stirred for 30 minutes at room temperature, then 30wt 2.36 g of diphenyl carbonate (DPC) -methylisobutylketone (MIBK) solution (containing 4 mmol of diphenyl carbonate) was added, and the mixture was stirred at room temperature for 3 hours for reaction to prepare a reaction solution. 24 g of methyl isobutyl ketone was added to the reaction solution obtained in the above step (1), 18 g of 1 mol / L sulfuric acid was added, and the reaction was stopped by stirring. In the step (2), the reaction solution to which acid was added was transferred to a separating funnel, and the aqueous phase was removed after stirring. Further, 18 g of 1 mol / L sulfuric acid was added again, The aqueous phase was removed (ie, a total of two washes of sulfuric acid were added), followed by the addition of 20 g of water and stirring, followed by the removal of the aqueous phase and further washing of the organic phase with 20 g of water twice After that, 130 g of methyl isobutyl ketone was added to the obtained organic phase, and then the solution was concentrated under reduced pressure until the weight of the solution became 52.3 g with an evaporator The water contained in the solution was removed. 52.3 g of the reaction solution obtained in the above step (3) and 0.89 ml of oleic acid were added to a sufficiently dried glass flask, and then the flask was heated in an oil bath and heated to an internal temperature of 102 ° C. And the mixture was stirred for 12 hours. Thereafter, the obtained reaction solution was cooled, and NMR measurement was carried out. As a result, a valine-N-carboxylate anhydride was produced at a yield of 63percent. The reaction solution obtained in the above step (4) was concentrated under reduced pressure until the liquid weight became 3.34 g with an evaporator, then 9 ml of dibutyl ether was added, then 90 ml of n-hexane was added, The precipitated white solid was recovered by suction filtration, and 0.16 g of valine-N-carboxylate anhydride was obtained (purification yield: 44percent).The precipitated solid was recovered in the same manner as in Example 1 except that 9 ml of diethyl ether was used instead of dibutyl ether in the step (5) in Example 1 to obtain 0.26 g of valine-N-carboxy anhydride Things were obtained.
82
[ 1295-35-8 ]
[ 14825-82-2 ]
(S)-[-NiNHC(H)RC(O)NHCHR-](x), R=CH2C6H5[ No CAS ]
polymer, copolymer, average number of 1-benzyl-L-histidine residues of 32, average number of L-phenylalanine residues of 6; monomer(s): 1-benzyl-L-histidine N-carboxyanhydride hydrochloride; L-phenylalanine N-carboxyanhydride[ No CAS ]
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