A, Alpha-phenyl-substituted Cinnamic Amide Synthesis And Vasodilator Activity Of Two Paf Receptor Antagonists - Fong Ammonia Synthesis Of Ketones And Structure-activity Relationship Study, The Total Synthesis Of Natural Products Of Wild Chrysanthemum Alco

Recently, research on Potassium Channel Opener (KCO) has been the highlight in the field of cardiovascular drug development. Based on the structure of the lead compound N-4-methoxybenzoyl-N'-cinnamylpiperazine,a series ofα-phenylcinnamides were designed, synthesized and screened as potential vasodilative and antihypertensive agents. Thirteen a-phenylcinnamic acids were synthesized as intermediates through classic Perkin reaction and the configuration of their double bond were determined by NOE difference spectra. The plausible way of cleavage for the formation of the specific fragment peak in the MS of the a-phenylcinnamic acid was further verified and the influence of ortho-group of the cinnamic bezene ring on the chemical shift of the olefinic proton was discussed. Twenty-fourα-phenylcinnamide(unreported) were prepared by means of acyl chloride method and mixed anhydride method. Vasodilative activity assays were conducted for the target compounds and the results indicated that several compounds demonstrated superior pharmacological profiles to the lead compound, among which compound RX-11 was further evaluated and found to be indicative of potential KCO activity. Preliminary SAR ofα-phenylcinnamides was discussed herein.Platelet Activating Factor (PAF) , a far-ranging biological agent, plays a major role in the pathogenesis of several diseases such as anaphylaxis, inflammation and cardiovascular diseases. In search for highly effective but low toxic PAF-receptor antagonists, a series of aromatic aminoketones were designed, synthesized and screened. In the course of synthesis, we investigated the Mannich reaction conditions and probed into the formation mechanism ofα-methylene-β-aminoketones(IM). Twenty-oneβ-aminoketones(MA) and twenty-twoα-methylene-β-aminoketones(IM) were synthesized via modified Mannich reaction, among which three compounds were deuterium-labeled. All the IM type compounds were unreported and their MS and ~1HNMR were studied. On the basis of pharmacological assays for inhibitory effects on release ofβ-glucuronidase and lysozyme, preliminary structure-activity relationship of aromatic aminoketones as potential PAF-receptor antagonist was discussed The topological similarity between the three-dimensional structure of compound IM-2 with that of clinical-applied Ginkgolide B was tentatively studied by means of Molecular Mechanics. In addition, a few compounds were screened for cytotoxity and vasodilative activity.Chrysanthemol, a trans-eudesmane type sesquiterpene from Chrysanthemum indicum L., possesses certain anti-inflamatory activity. Its total synthesis was approached from two angles and finally accomplished in ten steps from R-(+)-carvone viaα-eudesmol as the key intermediate. The overall yield is 2.4% and the analytic data of the synthetic target compound was identical with that of natural chrysanthemol. Seven. intermediary compounds were tested for inhibitory effects on the carragenan- induced swelling of mouse paw but demonstrated no obvious activities.