4363-94-4Relevant articles and documents
Synthetic ferrocenic mefloquine and quinine analogues as potential antimalarial agents
Biot, Christophe,Delhaes, Laurence,MacIejewski, Lucien A.,Mortuaire, Marlene,Camus, Daniel,Dive, Daniel,Brocard, Jacques S.
, p. 707 - 714 (2000)
A few years ago we proposed a strategy for the synthesis of new ferrocene-chloroquine analogues replacing the carbon chain of chloroquine by hydrophobic ferrocenyl moieties. Now, this strategy has been applied to the antimalarial amino-alcohols class to afford new potentially active analogues of mefloquine and quinine bearing a substituted ferrocenic group. The pathway used for the synthesis of the mefloquine analogues includes the coupling of an aminomethyl substituted ferrocene carboxaldehyde with a lithio quinoline compound. On the other hand, the synthesis of quinine analogues was ensured by the 'inverse' reaction of a lithio aminomethyl ferrocene with a quinoline carboxaldehyde. The configurations of each diastereoisomer were unambiguously determined by spectroscopic data. The mechanistic interpretations were fully discussed. Ferrocenyl analogues of mefloquine and quinine exhibited a lower antimalarial activity than mefloquine and quinine themselves. Comparing optical isomers, those isomers dissimilar to ferrocenyl derivatives presented better antimalarial activities than those similar to ferrocenyl. (C) 2000 Editions scientifiques et medicales Elsevier SAS.
Direct access of the chiral quinolinyl core of cinchona alkaloids via a br?nsted acid and chiral amine co-catalyzed chemo- and enantioselective α-alkylation of quinolinylmethanols with enals
Tong, Mengchao,Wang, Sinan,Zhuang, Jinchen,Qin, Cong,Li, Hao,Wang, Wei
, p. 1195 - 1199 (2018/02/23)
A strategy for the facile construction of the chiral quinolinylmethanolic structure, a core featured in cinchona alkaloids, is reported. A new reactivity is harnessed by TfOH-promoted chemoselective activation of α-C-H over O-H bond in quinolinylmethanols. The new reactivity is successfully engineered with an iminium catalysis in a synergistic manner to create a powerful conjugate addition-cyclization cascade process for synthesis of chiral quinoline derived π-butyrolactones in good yields and with good to excellent enantioselectivities. The method enables the first total synthesis of natural product broussonetine in three steps.
Scope of stereoselective Mn-mediated radical addition to chiral hydrazones and application in a formal synthesis of quinine
Friestad, Gregory K.,Ji, An,Baltrusaitis, Jonas,Korapala, Chandra Sekhar,Qin, Jun
, p. 3159 - 3180 (2012/05/20)
Stereocontrolled Mn-mediated addition of alkyl iodides to chiral N-acylhydrazones enables strategic C-C bond constructions at the stereogenic centers of chiral amines. Applying this strategy to quinine suggested complementary synthetic approaches to construct C-C bonds attached at the nitrogen-bearing stereogenic center using multifunctional alkyl iodides 6a-d as radical precursors, or using multifunctional chiral N-acylhydrazones 26a-d as radical acceptors. These were included among Mn-mediated radical additions of various alkyl iodides to a range of chiral N-acylhydrazone radical acceptors, leading to the discovery that pyridine and alkene functionalities are incompatible. In a revised strategy, these functionalities are avoided during the Mn-mediated radical addition of 6d to chiral N-acylhydrazone 22b, which generated a key C-C bond with complete stereochemical control at the chiral amine carbon of quinine. Subsequent elaboration included two sequential cyclizations to complete the azabicyclo[2.2.2]octane ring system. Group selectivity between two 2-iodoethyl groups during the second cyclization favored an undesired azabicyclo[3.2.1]octane ring system, an outcome that was found to be consistent with transition state calculations at the B3LYP/6-31G(d) level. Group differentiation at an earlier stage enabled an alternative regioconvergent pathway; this furnished the desired azabicyclo[2.2.2]octane ring system and afforded quincorine (21b), completing a formal synthesis of quinine.
