Research Projects

Natural products being scarcely available from natural sources, their laboratory synthesis for bioactivity evaluation gains significance. The guaianolides and acetogenins have been shown to possess important medicinal properties including anticancer activities. Cancer is a global treat and needs new drugs to be developed to meet the anti-drug resistance that is increasing every day to available drugs. Combination therapies using multiple drugs is also looked upon as an alternative to combat drug resistance. We have developed new indigenous strategies focusing on step-economy toward synthesis of various natural products. The allylic transformations involving diastereoselective allylation of functionalized aldehydes with allyl bromolactones directly gives the intermediates for rapid assembly of the 5,7,5-rings system present in various guaianolides. Hence, we propose this strategy toward the synthesis of selected molecules like geigerin, mikanokryptin, argyins H-K, stemona alkaloids, etc. Also, the diastereoselective and stereodivergent allylic alkoxylation to synthesize both cis- and trans-2,5-tetrahydrofurans can enable the synthesis of various acetogenins. We propose to utilize this strategy toward the synthesis of gigantetrocin B, muricatetrocin, phytofurans, isofurans, dihomo-isofurans, itomanallene B and related molecules. Our own strategies based on diastereoselective allylation with functionalized allyl bromolactone have resulted in protecting group free and step economic total synthesis of grosheimin and eupalinilide E. This work is published in J. Org. Chem. 2024, 89, 815 as cover page article. Also, the diastereoselective allylic alkoxylation preliminary work is published in Chem. Commun. 2023, 59, 2007. Both the strategies have excellent potential for synthesis of proposed guaianolides and acetogenins natural products. The major outcome of this proposal would result in the total synthesis of various complex guaianolides having interesting bioactivities. Also, the synthesis of Stemona alkaloids is a good fit in the established diastereoselective allylation chemistry. The allylic alkoxylation strategy will result in the synthesis of several phytofurans, isofurans and dihomo-isofurans of medicinal value. The synthesis of acetogenins will pave a path for synthesis of various new molecules that are isolated and not yet synthesized in this class of bioactive compounds. The strategies developed are step-economic, convergent and can be utilized in total synthesis of various guaianolides, acetogenins and their analogues for bioactivity studies. Total synthesis work proposed in this project will be very useful for training of many research scholars in organic synthesis, an important area for drug development and medicinal chemistry. Most of the synthetic and bioactivity results will be published in reputed organic, bio-organic and medicinal chemistry journals. The research work will also be presented in national and international conferences. This will help to foster future collaboration at both academic and industrial level. New projects based on this study will be initiated.