Title : Design and strategic synthesis of some biologically important marine natural products and their fluorinated analogues
“The need for efficient and practical synthesis of biologically active molecules remains one of the greatest intellectual challenges with which chemists are faced in the 21st Century”.
Throughout the ages humans have relied on Nature to cater for their basic needs, not the least of which are medicines for the treatment of a wide spectrum of diseases.1-2 The synthesis of complex natural products continues to occupy an important position in organic chemistry research, not only because nature provides us with some of the most synthetically challenging molecules that we can ever aspire to synthesize, but also because research in this area frequently drives important breakthroughs in methodology. Structurally complex, biologically active naturally occurring substances of marine origin continue to spur the interest of both chemists and biologists as they demonstrate antiviral, antimicrobial, anti-oxidant, and many more biological activities3-5. Marine derived pharmaceuticals have been used as source of chemical diversity in drug discovery programmes. This was an important area to work on as the major challenge with the biologically active isolated natural products is their limited availability through natural resources and their isolation is very tedious and time consuming process6. Further, they are usually isolated in very small quantities, hindering further studies to establish their biological activities as well as structural modifications and their constant supply from natural sources is problematic or virtually impossible. In addition, chemoselective derivatization of marine natural products themselves is usually quite difficult because of their sensitive and elaborate molecular structures, and access to their structural analogs is severely restricted in many cases.
Therefore, chemical synthesis of marine compounds in larger quantities and by sufficient means is necessary to investigate their biological implications and this strategic synthetic methodology is focused in our lab7-9. We are mainly interested in natural products possessing Indole and β-carboline moieties and have extended our synthetic strategies for the synthesis of their fluorinated analogues. Synthetic utility of various functionalities such as -NH2, -COOH and -Br which are extensively used in coupling reactions has been explored in the total synthesis and which may be used in synthesizing diversely substituted analogues of many natural products and may prove helpful in establishing SAR studies. Further, considering significance of fluorine incorporation in heterocycles and taking an overview on their biological activities, synthesis of fluorinated analogues of some marine natural products is planned. An understanding of mechanism, coupled with knowledge of physicochemical properties affected by fluorine substitution has aided in rational drug design of many pharmaceutical agents.