Synthesis of isocryptolepine and analogues for antimalarial evaluation
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Malaria is considered a serious global health concern, causing 445 000 deaths annually. With the increasing apperance of drug resistant cases of Plasmodium strains, discovery of new treatments are of paramount importance. The natural product isocryptolepine (4) is known to display potent antimalarial activity, with preliminary studies indicating that its analogues may display even greater activities. Isocryptolepine (4) was successfully synthesized in four steps starting from 3-bromoquinoline in a total yield of 31%. Pd(OAc)2 was examined as a possible catalyst for the microwaveassisted ring closure to obtain 5H-indolo[3,2-c]quinoline, where PdCl2(dppf) performed better at low scales. Attempts to utilize both Pd(OAc)2 and PdCl2(dppf) to achieve a gram-scale synthesis of the natural product 4 were unsuccessful. Two novel C6-alkylated isocryptolepine analogues were synthesized in six steps starting from 3-bromoquinoline in total yields of 25-45% and 3-4% for analogues 41a and 41b, respectively. The key synthetic strategies in the pathway towards analogues 41 include N-oxidation, iodine-catalyzed alkenylation, Suzuki-Miyaura cross-coupling reaction, Pd/C catalyzed reduction, tandem C-H activation and C-N bond formation and N-methylation.
Master's thesis in Environmental technology