Towards the Total Synthesis of the Baulamycin A

Abstract

Baulamycin A and B are a new structural class of antibiotics. They come from marine microbial-derived natural product extracts collected in Costa Rica, Panama and Papua New Guinea. From the two types of Baulamycin, Baulamycin A is the one that we are going to synthesize because it is able to inhibit microorganisms resistant to Staphylococcus aureus (MRSA), the main cause of serious hospital infections. Furthermore, it has been found that Baulamycin is also able to inhibit the dangerous and deadly bacterium Anthrax, a bio-terrorist potential agent that is cured with extreme difficulty by common antibiotics. Unfortunately, Baulamycin A was isolated in a very small quantity and its potential antibiotic capacity has not been studied nor has done activity studies. Its structure has been proposed only by the analysis of its spectroscopy data. However, the main problem to synthesize this molecule is that it owns 7 stereocenters. In order to confirm the structure and test its effectiveness in a comprehensive manner as possible drug, the total synthesis is essential. My research team in Bologna embarked on the total synthesis of this antibiotic and they have identified two possible precursors for the total synthesis. Synthon B can be prepared through the execution of three consecutive organocatalytic reactions developed in our laboratories.My research in this project is to scale up the reactions to synthon B, try to synthesize synthon A and control the relative configuration of the newly formed stereogenic centers. Also, we will try to increase the yield obtained in each step in order to get more product. However, very recently a research group of the Department of Organic Chemistry of the Indian Association for the Cultivation of Science of Jadavpur in Kolkata (India) have published in the Journal of Organic Chemistry an article on the Total Synthesis of Reported Structure of Baulamycin A and its Congeners. This paper disclosed that the reported structure of Baulamycin A needs to be revised, as the spectroscopic data described for the synthetic compound are not identical with the real Baulamycin A.