Synthesis And Structure-Activity Relationship Of Anti-allergic Component Scrodentoid A In Scrophularia Dentate And Its Analogs

Aims:With the development of modern society,allergies have become the sixth largest disease in the world,seriously threatening the health and life of human beings.In terms of drug treatment,anti-histamine drugs are mainly used clinically,and their anti-allergic effects are relatively simple,which can’t meet complex allergy symptoms.In allergic reactions and inflammatory reactions,mast cells act as effectors,which plays an important role.effect.Therefore,the discovery of safe and effective cell stabilizers is of great significance for the development of anti-allergic drugs.Clinically,traditional Chinese medicine has a long history of preventing and treating allergic diseases.In recent years,studies have shown that more and more active ingredients of traditional Chinese medicines show anti-allergic biological activities.Our research group found that Scrodentoid A extracted from the Chinese medicine Scrophularia dentate has obvious anti-allergic activity in cell and animal experiments,has the function of stabilizing mast cells,and is a natural anti-allergic active ingredient.My job is to fully synthesize the natural product Scrodentoid A,at the same time derivatize its structure,evaluate its activity,clarify the structure-activity relationship of Scrodentoid A,and find Scrodentoid A analogues with better biological activity for subsequent pharmacological experiments and drugs.Metabolic kinetic experiments provide a material basis.Method: 1.Determine the Hagemann’s ester and o-isopropylphenol as raw materials by reverse synthesis analysis.2.The racemic Scrodentoid A is synthesized by an organic chemical method.3.Using the BMMCs mast cell activation model experiment to detect the difference in anti-allergic activity between racemic Scrodentoid A and Scrodentoid A.4.Using the BMMCs mast cell activation model experiment,a series of structural analogs of Scrodentoid A were designed and synthesized,and the anti-allergic activity of the analog was evaluated to clarify the structure-activity relationship of Scrodentoid A.Result: 1.The complete synthesis of the racemic Scrodentoid A was completed for the first time.The longest linear step was 12 steps,the total yield was 1.94%.The product was identified by nuclear magnetic resonance and mass spectrometry.2.Using the BMMCs mast cell activation model,the anti-allergic activity test results showed that the natural product Scrodentoid A inhibited the release of β-hex by 62.5%,and the racemic Scrodentoid A inhibited the release of β-hex by 65%.Both anti-allergic activities are comparable.3.A total of 12 structural analogs of A,B,and C rings were designed and synthesized,and the obtained analogs were confirmed to be structurally correct by NMR and MS.4.According to the experimental results of BMMCs mast cell activation model,the structure-activity relationship of anti-allergic activity of Scrodentoid A and its analogues was preliminarily summarized.Conclusion:The starting material was determined to be ethyl 2-methyl-4-carbonyl-2-cyclohexene-1-carboxylate and 4-(2-bromoethyl)-2-isopropyl-by organic synthesis cleavage.1-methoxybenzene.The total synthesis of the racemic Scrodentoid A was first achieved by organic chemistry.The longest linear step was 12 steps with a total yield of 1.94%.A total of 12 Scrodentoid A analogs were obtained by modification,design and synthesis of the A,B,and C ring structures of the racemic Scrodentoid A.Using the BMMCs mast cell activation model experiment,the anti-allergic activity of the racemic Scrodentoid A and its analogs was evaluated.The structure-activity relationship of the anti-allergic activity of the Scrodentoid A analog was preliminarily summarized.We found the racemic Scrodentoid A.It has a certain degree of antiallergic activity,which is equivalent to the anti-allergic activity of the natural product Scrodentoid A.At the same time,the methyl group of the A ring and the hydroxyl group of the C ring have a crucial influence on the anti-allergic activity of the Scrodentoid A.These analogs were confirmed to be structurally correct by nuclear magnetic resonance and mass spectrometry.