Study On The Total Synthesis Of Garcibracteatone A And Its Related Methodologies On Gold Catalysis

With the revolution of a hundred million years, natural products posse a lot of advantages such as stability of the structure, diversity of the skeleton and broad spectrum of biological activity compared with synthesized molecules. Because of the these advantages, natural products have becoming highly favored by chemists and medicinal chemists. This article describes the total synthesis of new natural product Garcibracteatone A and several methodologies developed based on this natural product.For the synthesis of the Garcibracteatone A, we envisioned a Michael addition/aldol reaction/esterification reaction as the key step and designed three generations of synthetic routes based on the key strategy. Each of the routes is the optimized version of earlier route and good results were obtained. Finally, we synthesized the left wing and the right wing of the natural product using cheap 1,4-Butyrolactone as the starting material through 8 and 10 steps respectively.During the course of total synthesis, we discovered that ring strain may disturb the pathways of cyclization reactions, and designed a strain contained propargyl vinyl ethers as the substrates. Under the catalysis the gold catalysts, the regioselectivity of this strained substrate was totally changed from 5-exo-trig to 6-endo-dig. We explored the scopes of this methodology and discussed the mechanism of this reaction thoroughly assisted by computational chemistry. Also, the application of this methodology was developed. Based on the previous research, we developed nucleophile mediated substituent controlled cyclization. The mechanism of this methodology was thoroughly studied and a series of deuterated experiment was conducted. The synthesized compounds were subjected to the preliminary antibacterial test. Finally, a one-pot synthesis of biaryls was developed based on the previous study using propargyl vinyl ethers as the substrates. The reaction condition was screened carefully and the scopes of this reaction were tested through the use of symmetrical and unsymmetrical dienophiles.