Synthesis
Using L-arginine and p-toluenesulfonyl chloride as starting materials, and alcohol as the reaction solvent, TOS-ARG-OME HCL was prepared in one step [1]. The synthesis reaction formula is shown in the figure below:
Figure 1 Synthesis of NA-P-Toluenesulfonyl-L-arginine methyl ester hydrochloride: 26.25 g (0.25 mol) of L-arginine and 62.5 mL (0.25 mol) of 4 mol/L sodium hydroxide solution were added to a 500 mL four-necked flask equipped with a mechanical stirrer, thermometer, pH meter, and dropping bottle. The mixture was stirred in a cold trap to ensure complete reaction of arginine and sodium hydroxide. 2.7 g of tetrabutylammonium hydrogen sulfate, 50 mL of water, and methanol were added to the flask, and the mixture was stirred to dissolve the phase transfer catalyst. 42.5 mL (0.3 mol) of p-toluenesulfonyl chloride was slowly added dropwise below 0 °C. Later, a borate buffer solution with pH=9 was continuously added to adjust the pH to approximately 9. After the p-toluenesulfonyl chloride was completely added, the temperature was raised to 15 °C, and the reaction was continued with stirring for 3 hours. TLC analysis confirmed the completeness of the reaction. The mixture was washed with diethyl ether (2 × 20 mL), and the ether layer was discarded. 6 mol/L hydrochloric acid was slowly added dropwise with constant stirring to adjust the pH of the aqueous phase to 2. Stirring was continued for 20 min, resulting in the precipitation of a white solid. The solid was extracted with ethyl acetate (3 × 30 mL), and the ethyl acetate organic layer was separated. The solid was washed with 5% sodium chloride solution and water until neutral, dried over anhydrous sodium sulfate, and the ethyl acetate was removed by rotary evaporation, yielding an oily liquid. The liquid was frozen overnight, and a large amount of white solid precipitated. A large amount of petroleum ether was added, and the mixture was stirred to obtain a white powdery solid. The powder was filtered, washed with petroleum ether, and dried to obtain TOS-ARG-OME HCL.
References
[1] XING ZENG. Pharmacologic inhibition of the anaphase-promoting complex induces a spindle checkpoint-dependent mitotic arrest in the absence of spindle damage.[J]. Cancer Cell, 2010, 18 4: 382-395. DOI:
10.1016/j.ccr.2010.08.010[2] XING ZENG Randall W K. An APC/C inhibitor stabilizes cyclin B1 by prematurely terminating ubiquitination[J]. Nature chemical biology, 2012, 8 4: 383-392. DOI:
10.1038/nchembio.801
