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CAS No. : | 745017-94-1 | MDL No. : | MFCD25976742 |
Formula : | C39H65N5O8 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | MFRNYXJJRJQHNW-DEMKXPNLSA-N |
M.W : | 731.96 | Pubchem ID : | 10395173 |
Synonyms : |
MMAF
|
Chemical Name : | (S)-2-((2R,3R)-3-((S)-1-((3R,4S,5S)-4-((S)-N,3-Dimethyl-2-((S)-3-methyl-2-(methylamino)butanamido)butanamido)-3-methoxy-5-methylheptanoyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanamido)-3-phenylpropanoic 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 |
---|---|---|
With sodium cyanoborohydride; acetic acid; In N,N-dimethyl-formamide; at 20℃; for 2h; | To a solution of compound 12-6 in DMF was added formylaldehyde (3eq) and 20 eq of acetic acid, followed by addition of 2 eq of sodium cyanoborohydride. The resulting mixture was stirred at ambient temperature for 2 hours. The reaction mixture was diluted with water and purified by HPLC to give compound 12-7. | |
With sodium cyanoborohydride; acetic acid; In N,N-dimethyl-formamide; for 2h; | To a solution of compound 12-6 in DMF was added formylaldehyde15 (3eq) and 20 eq of acetic acid, followed by addition of 2 eq of sodium cyanoborohydride. Theresulting mixture was stirred at ambient temperature for 2 hours. The reaction mixture was dilutedwith water and purified by HPLC to give compound 12-7. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Ca. 100% | With hydrogenchloride; In 1,4-dioxane; water; at 20℃; for 0.583333h; | (S)-2-((2R,3R)-3-((S)- 1 -((6S ,9S, 12S, 1 3R)- 12-((S)-sec-butyl)-6,9-diisopropyl- 13- methoxy-2,2,5,11 -tetramethyl-4,7, 1 0-trioxo-3 -oxa-5 ,8,11 -triazapenta-decan- 15- oyl)pyrrolidin-2-yl)-3 -methoxy-2-methylpropanamido)-3 -phenylpropanoic acid (25 mg,0.030 mmol) in the mixture of HC1 (conc. 0.3 ml) and 1,4-dioxane (0.9 ml) was stirred at RT for 35 mm. The mixture was diluted with EtOH (1.0 ml) and toluene (1.0 ml), concentrated and re-evaporated with EtOH/toluene (2:1) to afford the title compound as a white solid (22 mg, -400percent yield) for the next step without further purification. LC-MS (ESI) mlz calcd. for C39H66N508 [M+Hj: 732.48, found: 732.60. |
With hydrogenchloride; In 1,4-dioxane; at 20℃; for 2h; | Compound 12-5 was dissolved in 4N HCl/Dioxane. The reaction mixture was stirred at room temperature for 2 hours and concentrated in vacuo and purified by HPLC to give 150mg of compound 12-6. | |
150 mg | With hydrogenchloride; In 1,4-dioxane; at 20℃; for 2h; | Compound 12-5 was dissolved in 4N HClDioxane. The reactionmixture was stirred at room temperature for 2 hours and concentrated in vacuo and purified by HPLCto give 150mg of compound 12-6. |
With hydrogenchloride; In 1,4-dioxane; water; at 20℃; for 0.583333h; | Compound 330 (25 mg, 0.030 mmol) in the mixture of conc. HCl (0.3 ml) and 1,4-dioxane (0.9 ml) was stirred at r.t. for 35 min. The mixture was diluted with EtOH (1.0 ml) and toluene (1.0 ml), concentrated and co-evaporated with EtOH/toluene (2:1) to afford the title compound 331 as a white solid (22 mg, ~100percent yield), which was used in the next step without further purification. LC-MS (ESI) m/z calcd.for [M+H]+: 732.48, found: 732.60. | |
56 mg | With trifluoroacetic acid; In dichloromethane; at 20℃; for 5h; | General procedure: LiOHH2O (5 mg, 0.12 mmol) was added to a solution of 18a (30 mg, 0.06 mmol) in MeOH (2 mL) and water (1 mL) at room temperature. After stirring at room temperature for 3 h, the reaction mixture was concentrated in vacuo and the obtained residue was redissolved in water (5 mL). The mixture was acidified to pH 4e5 by addition of 1 N HCl and a white precipitate was formed. The solid was collected and dried to afford the free acid species as a white solid. The obtained solid was dissolved in CH2Cl2 (2.5 mL), TFA (68 mg, 0.6 mmol) was added and the reaction mixture was stirred at room temperature for about 5 h and then concentrated under reduced pressure. The crude residue was purified by preparative HPLC (SB-C18 column, 5 mm, 9.4 250 mm, 40percent CH3CN/60percent H2O) to yield the desired product (24 mg, 93percent over 2 steps) as a white solid; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
[0071] Example 6. Synthesis of 39-(2,5-dioxo-3,4-bis(2-pyridylsulfanyl)pyrrolyl)- -dodecaoxanonatriacontanoyl-MMAF [dPSPEG-MMAF] : [0072] 39-(2,5-Dioxo-3,4-bis(pyridin-2-ylthio)-2,5-dihydro-lH-pyrrol-l-yl)- 3,6, 9, 12,15, 18,21, 24,27, 30,33, 36-dodecaoxanonatriacontanoic acid was added to a clean, flame- dried 50 mL round bottom flask, and the carboxylic acid was activated with NHS in 3 mL of DMF in the presence of DCC. MMAF was predissolved in about 1 mL DMF and transferred to the NHS- activated acid via 22 gauge needle. DIPEA was added to the reaction mixture and stirred overnight. The crude reaction mixture was purified by reverse-phase HPLC on a 21.2 mm x 50 mm Agilent PREP-C18 column at a flow rate of 35 mL/min over 20 column volumes (about 30 minutes of gradient time). Enriched fractions were identified, pooled and lyophilized to give the dPSPEG- MMAF conjugate as a white semi-solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium cyanoborohydride; In dimethyl sulfoxide; at 60℃; for 72h; | sodium cyanoborohydride (200fImol) and 6-O-propargyl-D-galactose (45flmol) were added to the solution of MMAF (2.7fImol) in dimethylsulphoxide (0.7m1) . The mixture was stirred at 60°C for three days. |