Applications Of LC/MS In Combinatorial Synthesis And Isolation Of Natural Products

This thesis is divided into two parts dealing withhigh-throughput LC/MS purification of combinatorial library usingmass-based fraction collection and a high-throughput method forproduction and analysis of natural products library for drugdiscovery.In the first part, the author has optimized the LC/MSpurification platform configurations and developed ahigh-throughput purification method of combinatorial library usingmass-based fraction collection. Enforcement of one fraction persample collection has greatly enhanced the purification efficiencyand simplified the post-purification process. This approachworked extremely well in our high throughput environment thatdealt with fifty compounds per day. This approach produced overfour hundred high quality compounds by purifying twopurine-libraries with purity over 95% by ELSD which is currentlythe most stringent quality criteria applied in a high throughputmode to synthetic compounds.In the second part, the high-throughput methods wereapplied to production, analysis, and characterization of librariesof natural products in order to accelerate the drug discoveryprocess for high-throughput screening in the pharmaceutical andbiotechnology industries. This library production integrated...