Mapping the reactivity of the quinoline ring-system – Synthesis of the tetracyclic ring-system of isocryptolepine and regioisomers

Synthesis and Evaluation of the Tetracyclic Ring-System of Isocryptolepine and Regioisomers for Antimalarial, Antiproliferative and Antimicrobial Activities

“…Applying the nitrene insertion appr to biaryls 15, 17, and 19, we were able to significantly improve the yields of tetracycl and 20 compared to our previous endeavors (Scheme 3, previous yields in brackets) Following a literature procedure, neocryptolepine (2) was obtained in good yield sta from its precursor 13 (Scheme 4) [67]. (20) using a diazotization-azidation-nitrene insertion appr ets: yields from our previous endeavors [52]. Conditions: (i) HCl (37%), NaNO2 (0 (ii) 1,2-dichlorobenzene, 180 °C, 3 h. For the synthesis of compounds 15, 17, and 1 previous work [52].…”

“…The biological activities for the core structu sively studied while their regioisomers have bee novel pyridophenanthridine scaffold 4a (Figure represents an interesting target for biological eva eton may be regarded as a regioisomer to the pyr is illustrated in compound 5 in Figure 2), a wel notably known for exhibiting potent antiprolifer tolepine (1), nearly all naturally occurring pyrido intercalating agents, resulting in cytotoxic effect also possess the ability to inhibit topoisomerase profiles such as antibacterial, antifungal, a [53,56,57,[59][60][61]. Consequently, it is postulated thetic derivatives are pivotal for the future gener Recently, we described the preparation of s certain chemoisomers [52]. In this paper, we pre thetic strategies which allowed for the realizatio pounds 4b, 8, and 9) along with the N-alkylatio analogues (compounds 3b, 3c, 10, and 21).…”

“…In this paper, we pre thetic strategies which allowed for the realizatio pounds 4b, 8, and 9) along with the N-alkylatio analogues (compounds 3b, 3c, 10, and 21). Moreo along with our existing library of natural product in vitro antiplasmodial activity against Plasmodi Recently, we described the preparation of several isocryptolepine regioisomers and certain chemoisomers [52]. In this paper, we present modifications to our previous synthetic strategies which allowed for the realization of novel tetracyclic ring-systems (compounds 4b, 8, and 9) along with the N-alkylation of several compounds to furnish new analogues (compounds 3b, 3c, 10, and 21).…”

“…(20) using a diazotization-azidation-nitrene insertion appr ets: yields from our previous endeavors [52]. Conditions: (i) HCl (37%), NaNO2 (0 (ii) 1,2-dichlorobenzene, 180 °C, 3 h. For the synthesis of compounds 15, 17, and 1 previous work [52].…”

“…Similarly, t tolepine (1), nearly all naturally occurring pyridoacridines have been shown to act a intercalating agents, resulting in cytotoxic effects in cultured tumor cells [54,55,58 also possess the ability to inhibit topoisomerase II [53,58] and further contain bio profiles such as antibacterial, antifungal, antiviral, antiparasitic and inse [53,56,57,[59][60][61]. Consequently, it is postulated that the pyridoacridines and the thetic derivatives are pivotal for the future generation of medicinal compounds [5 Recently, we described the preparation of several isocryptolepine regioisome certain chemoisomers [52]. In this paper, we present modifications to our previo thetic strategies which allowed for the realization of novel tetracyclic ring-system pounds 4b, 8, and 9) along with the N-alkylation of several compounds to furni analogues (compounds 3b, 3c, 10, and 21).…”