My group has designed and synthesized artemisinin-based hybrid molecules as novel antimalarials having dual targets in the parasite such as inhibition of falcipain-2, a P. falciparum cysteine protease involved in haemoglobin degradation and blocked the hemozoin formation in the food-vacuole. The synthesized hybrid compounds effectively inhibited the survival of ring stage parasite for laboratory adapted artemisinin-resistant parasite lines as compared to artemisinin. These hybrid molecules showed complete parasite clearance in vivo using P. berghei-mouse malaria model. The hybrid molecules blocked multiple steps of a pathway and showed synergistic efficacies and have less chance to induce resistance; hence these lead compounds can be developed as effective antimalarials to overcome the resistance developed by the parasites to the current antimalarials (WO 2019202609 A1 20191024).

Pilot scale transformation of artemisinin into compounds having potential antimalarial activity viz. diastereomeric mixture of a/b-arteether (30:70) was prepared for the completion of phase lll clinical trials. The drug has been approved by the Drug Controller of India for its clinical use. Our technology has been licensed to many pharmaceutical companies in India for commercial exploitation. It is being marketed in India as E-MalÔ by Themis Pharmaceuticals, India.

Developed a commercially viable process for the conversion of artemisinic acid, the most abundant secondary metabolite present in the plant A. annua to artemisinin, an antimalarial drug. This has resulted in the reduction of cost of production of artemisinin by economical utilization of other secondary metabolites (EP 908460 A1 19990414; US 5,955,084).

Developed a diastereoselective synthesis of b-arteether, an antimalarial drug currently being used to treat malaria and cerebral malaria (IN 2014DE03079 A 20160831).

Developed a process for the preparation of sodium b-artelinate, a water soluble potent antimalarial derivative of artemisinin (IN 185198 A1 20001202).

Biomimetic approach to organic synthesis leads to a deeper understanding of how nature operates and illuminates the potential of new chemical reactions. Biomimetic synthesis of complex and biologically important natural product, angiopterlactone B (a tricyclic ring system (A/B/C) having dual lactones flanking both sides of a tetrahydrofuran ring containing seven contiguous stereocenters) was achieved by a base catalyzed (TBAF) synthetic methodology for the construction of dual lactone tricyclic ring system by tandem ring contraction followed by oxa-Michael/ Michael addition reactions of 5,6-dihydropyron-2-ones. This is the first report of a synthesis, which demonstrates generation of seven adjacent chiral centers in one-pot utilizing substrates having only two chiral centers. Angiopterlactone B, its enantiomer and diastereomers have been synthesized using our developed methodology. The outcome of fusion of two lactones (A and C) to form the tricyclic ring is in a cis-fashion in all the synthesized compounds irrespective of the streochemistries of the starting 5,6-dihydropyran-2-ones.

We have accomplished biomimetic synthesis of complex and biologically important natural products (±)-incarvilleatone and (±)-incarviditone by employing base catalyzed Rauhut-Currier dimerization/oxa-Michael/aldol strategy.