Synthese Of N-(4,5-dibromine-pyrrole-2-carbonyl)-L-valine Acid Methyl Esters And The Research Of Its Pharmacology Characteristic

Aldisin is a pyrrololactam compound isolated from the marine sponge phacellis fusca Schmidt collected from the South China Sea. Most of Aldisins synthetic derivatives show anti-cancer bioactivities in vitro. The thesis describes the syntheses ofAldisins dericatives that is N-(4, 5-dibromine-pyrrole-2-carbonyl)-L-valine acid methyl esters by refinement multi-step reaction with the economic and convenient compounds of pyrrole and trichloroacetic acid as starting materials. There are two parts of the thesis.In Part One, the research on the isolations, bioactivities and syntheses of the N-(4, 5-dibromine-pyrrole-2-carbonyl)-L-valine acid methyl esters was reviewed. Based on the previous route, the scheme was adapted and optimized.N-(4, 5-dibromine-pyrrole-2-carbonyl)-L-valine acid methyl esters was synthesized in higher yields via in reagent composed of a 1.5: 1: 2 solution by mol of spasmolytol, 4, 5-dibromo-2-(trichloroacetyl)pyrrole and valine acid methyl esters, and to keep on 24 hours is the reasonable time for the reaction. The N-(4, 5-dibromine-pyrrole-2-carbonyl)-L-valine acid methyl esters was obtained in 94.3ï¼…yield, 13.4ï¼…elevated. In the whole synthetical reaction, the N-(4, 5-dibromine-pyrrole-2-carbonyl)-L-valine acid methyl esters was obtained in 91.56ï¼…yield, 11.95ï¼…elevated.In Part Two, the filtration of anti-cancer activity was determined by MTT[3-(4, 5-dimethy-lthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] assay for N-(4, 5-dibromine-pyrrole-2-carbonyl)-L-valine acid methyl esters. The effect of N-(4, 5-dibromine-pyrrole-2-carbonyl)-L-valine acid methyl esters on the cell cycle distribution and qpoptosis were determined using propidium iodide staining and through flow cytometry.The inhibition rate of MCF-7 cell, CNE cell, HepG2 cell, LOVO cell, BEL-7402 cell and Hela cell were 81.5ï¼…, 70.6ï¼…, 81.9ï¼…, 68ï¼…, 63.4ï¼…and 80.1ï¼…at 50μg/ml. After these six kinds of cell were treated with N-(4, 5-dibromine-pyrrole-2-carbonyl) -L-valine acid methyl esters for 48h, the IC₅₀ were 11.3μg/ml, 17.18μg/ml, 15.3μg/ml, 4.04μg/ml, 10.98μg/ml and 4.09μg/ml.The examination of flow cytometry suggested, along with increasing the time of N-(4, 5-dibromine-pyrrole-2-carbonyl)-L-valine acid methyl esters-treated-Hela cells, the cell number increased at G1 phase and decreased at S and G2 phase; the percentage of apoptotic cells and the putrescent cells are all increased along with the increase of the dosage of N-(4, 5-dibromine-pyrrole-2-carbonyl)-L-valine acid methyl esters by the way of Annexin V/PI.