Research Projects

Some of the natural products of Amaryllidaceae family, such as galanthamine (1) and lycoramine (2) act as acetylcholinesterase inhibitors (AChEIs). Galanthamine (trade name is reminyl) is an alkaloid that has been extracted from plant sources and also synthesized for use in the treatment of mild to moderate Alzheimer's disease. Plants from the Amaryllidaceae family are known by humans since long back due to their pharmacological relevance. This family of natural product takes its name from the genus Amaryllis, hence the common name is Amaryllidaceae. Their interesting biological significance led to an intense research activity in this area which culminated with the isolation and chemical characterization of several structurally different classes of alkaloids. These alkaloids are spread all over the world. Like galanthamine (1a), there are a wide number of alkaloids isolated in plicamine (2a) alkaloids. These are having a similar all-carbon quaternary stereocenter at the pseudobenzylic position. Although, the biological activities of plicamine (2a) alkaloids are yet to be undertaken, it is hypothesized that because of their structural resemblance, these alkaloids are having interesting biological properties as galanthamine (1a). A great extent of synthetic studies directed towards the construction of these natural products has been done so far. Therefore, in addition to their relevant biological and pharmacological significance, galanthamine (1a) and plicamine (2a) alkaloids possess a highly sophisticated substitution pattern of their carbon skeleton. This is the reason which challenged and attracted synthetic organic chemists in establishing strategies for the total synthesis of this class of natural products which is evident from the reports available describing successful syntheses of several alkaloids isolated from Amaryllidaceae family. Towards this, development of methods to provide enantiopure compounds are always challenging and come at the fore front of organic synthesis. In this proposal the development of methodologies to construct plicamine (2a) and related alkaloids in enantiomerically pure form will be undertaken. A logical synthetic strategy has been proposed for the total synthesis of the Plicamine alkaloid (2a), employing Suzuki–Miyaura coupling, Mitsunobu reaction, carbonyl-ene reaction, allylic oxidation, and Pictet–Spengler cyclization. Later, we would like to collaborate with Biology to find out their biological potential.