Studt On Preparation Of Quaternized L-Lysine ?-NH₂ And Antithypertensive Activity

As an essential amino acid that constitutes human protein,L-lysine is involve d in various metabolic processes in the human body.At the same time,as lysine plays an increasingly important role in clinical treatment,people are gradually payi ng attention to the development of new drugs for lysine.In 1915,the first synthet ic quaternary ammonium salt compound was first produced.Since the quaternary a mmonium group present in the molecule was confirmed to have antibacterial activi ty,the quaternary ammonium salt compound has been favored by drug molecular designers.In this study,L-lysine was used as raw material to study the quaternizat ion reaction of?-NH₂,and the L-lysine quaternary ammonium salt compound 2-am ino-6-?trimethylammonium?was synthesized.The acid salt was studied and its anti hypertensive activity was studied.First of all,we used metal ion chelation protection to protect L-lysine?-NH₂a nd we optimized the type of metal ions,material ratio,system pH,reaction time a nd reaction temperature.As a result,we identified the optimal experimental protoc ol:Ni²⁺was the best metal ion,the feed ratio(n_Ni2+/n _L-Lys)was 1.2:1,the reaction pH was 10?±0.3?,the reaction temperature is 60°C,the reaction time was 2h,the yield was 87.4%.It was identified that the obtained metal ion chelate compound f ormula was Ni?Lys?₂·2H₂O.After that,Using Ni?Lys?₂·2H₂O as raw material,quaternization reaction of?-NH₂ was carried out using DMS,CH₃I and DMC as quaternization reagents respe ctively.The type,feed ratio,reaction temperature and catalyst type of quaternizatio n rea-gent were determined.The optimization experiment was carried out witht he dosage,reaction solvent type and reaction time,and the optimal process param eters were explored:DMC was the best quaternization reagent,the feed ratio(n _{DM C}:n_chelate)was16:1;the reaction temperature was 150°C.The catalyst was anhydrou s NaHCO₃?5.3 g?,the solvent was EtOH,the reaction time was 9 h,and theyield was 59.5%.The experimental data of the product 2-amino-6-?trimethylamm-onio?h exanoate was identified as follows:m.p.188.3-188.9°C;¹H NMR?500MHz,D₂O?,?:3.11?t,J=5.6Hz,1H,CH?,3.04?t,J=8Hz,2H,CH₂?,2.82?s,9H,CH₃?,1.45?m,4H,CH₂?,1.11?d,J=7.0Hz,2H,CH₂?;¹³C NMR?125MHz,D₂O?,?:178.20,65.08,53.99,51.70,31.14,21.03,20.56;ESI-MS?+?,m/z:189.15927[M+H]⁺,211.14105[M+Na]⁺.A systolic blood pressure?SBP?measurement experiment was performed on SHR rats and WKY rats by intragastric administration using isolated and purified2-amino-6-?trimethylammonio?hexanoate.The dose-effect relationship of 2-amino-6-?t rimethylammonium?hexanoate was determined by different dose test.Through as ingle administration test,it was found that the blood pressure lowering activity of the drug decreased with time,and the systolic blood pressure was minimized aft er 0.5h of administration.In conclusion,2-amino-6-?trimethylammonio?hexanoate ex hibited good hypotensive activity in both SHR rats and WKY rats.