Enantioselective Total Synthesis Of Bioactive Epoxyquinoid Natural Products

Abstract

Total synthesis of natural products with diverse architecture and varying degree of complexity is an area that has not only inspired and attracted several generations of organic chemists but also continues to enrich and refresh the foundations of organic chemistry itself, by offering new ideas and directions. Synthetic organic chemistry is perhaps the most formative and expressive enterprise of science in terms of its creative power and unlimited scope. Its impact on present day life and prosperity gets manifested when we see this science as the bedrock behind the production of pharmaceuticals, pesticides, fertilizers, nutritional products, high tech materials, polymers, cosmetics, plastics and clothing. Science of synthesis is also going to play an important role in the evolution of future societies based on the principles of the sustainable development. Being a precise science and a fine art, the endeavor of total synthesis is in a constant state of effervescence. Most significantly, the discipline is being continually challenged by new structures unraveled from the Nature’s bosom. The practice of total synthesis is being enriched constantly by new tools such as new reagents and catalysts as well as by analytical techniques. In fact, there has been a dramatic advancement in the recent past in the development of new synthetic protocols with high regio-, streo-, and enantiocontrol, which makes it possible to target natural product of any complexity. The demand for enantiomerically pure drugs, agrochemicals and food additives is growing, since pure enantiomers are often more target-specific and have fewer side effects than the recemic mixtures. As a result, synthesis of natural products in an enantioselective manner has been receiving increasing attention from synthetic chemists in recent years. Nature synthesizes a vast array of novel molecular structures in enantioselective fashion through several well-established biosynthetic pathways utilizing a few key building blocks. Among them mevalonate pathway to terpenes, shikimate pathway to aromatics, alkaloids and the polyketide pathway to aromatics, macrolides and related compounds are the most noteworthy. Polyketides, constitutes a large family of natural products built from acyl coenzyme A monomers and exhibit remarkable diversity both in terms of their structure and function. These natural products display a wide range of medicinally important activities such as antibiotic, anticancer, antifungal, hypolipidemic and immunosuppressive properties. In recent years, polyketide derived natural products embodying an epoxyquinone core, have been surfacing with increasing frequency from diverse natural sources. Both on account of their structural diversity and promising biological activity, polyketide derived epoxyquinoid natural products have evoked considerable attention from the synthetic community during the past few years. We too got enticed towards these natural products as an offshoot of ongoing research activity in the group. The present thesis entitled “Enantioselective Total Synthesis of Bioactive Epoxyquinoid Natural Products” is described in four chapters. Chapter 1: Enantioselective total synthesis of (+)-eupenoxide, (+)-6-epi-eupenoxide and (+)-phomoxide; Chapter 2: Enantioselective total synthesis of (−)-EI-1941-2; Chapter 3: Enantioselective total synthesis of (+)-integrasone. Chapter 4: Enantioselective total synthesis of (+)-hexacyclinol. It’s quite tempting to highlight the fact that while Nature might have used entirely different biochemical machinery to build up all these diverse natural products; but in the chemical laboratory all the syntheses have emanated from a single starting material, symbolizing the intrinsic power and versatility of chemical synthesis.