Chemistry and Biology of Cinchona Alkaloids

Kacprzak, Karol

doi:10.1007/978-3-642-22144-6_22

Cited by 51 publications

(35 citation statements)

References 230 publications

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“…Method 1: Synthesis of azides by ring opening of aziridines The solution of HN 3 (1.53 M in C 6 H 6 , 0.14 mmol, 200 µL) was added to the aziridines (0.07 mmol) by a syringe and the reaction mixture was stirred at RT overnight. Then, the solvent was evaporated under reduced pressure to give the corresponding azide.…”

Section: Synthesis Of Azidesmentioning

confidence: 99%

“…Enantiomerically pure β-amino alcohols belong to a privileged group of important and easily available organocatalysts and chiral building blocks [1,2]. Some of them are directly accessible as natural products (Cinchona [3] and Ephedra [4] alkaloids), the others are obtainable in a few simple synthetic steps, e.g., from natural amino acids. Recently, we have developed the synthesis of new chiral β-amino alcohols, containing metal-complexing 2-pyridyl and 6-(2,2 -bipyridyl) fragments [5].…”

Section: Introductionmentioning

confidence: 99%

“…2R)-Phenyl-1-[(S)-1-phenylethyl]-aziridine (2R,1 S)-8 (Method A): Colorless oil, 80 mg, 72% yield, [α] 20 D = −53 (c = 1.1, CHCl3 ), (lit [27]. [α] 23 D = −45 (c 1.5, CHCl 3 ), purified by column chromatography (SiO 2 , 30% AcOEt in hexane).…”

mentioning

confidence: 99%

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Regioselective and Stereodivergent Synthesis of Enantiomerically Pure Vic-Diamines from Chiral β-Amino Alcohols with 2-Pyridyl and 6-(2,2′-Bipyridyl) Moieties

2020

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In this report, we describe the synthetic elaboration of the easily available enantiomerically pure β-amino alcohols. Attempted direct substitution of the hydroxyl group by azido-functionality in the Mitsunobu reaction with hydrazoic acid was inefficient or led to a diastereomeric mixture. These outcomes resulted from the participation of aziridines. Intentionally performed internal Mitsunobu reaction of β-amino alcohols gave eight chiral aziridines in 45–82% yield. The structural and configuration identity of products was confirmed by NMR data compared to the DFT calculated GIAO values. For 1,2,3-trisubstituted aziridines slow configurational inversion at the endocyclic nitrogen atom was observed by NMR at room temperature. Moreover, when aziridine was titrated with Zn(OAc)2 under NMR control, only one of two N-epimers directly participated in complexation. The aziridines underwent ring opening with HN3 to form the corresponding azido amines as single regio- and diastereomers in 90–97% yield. Different results were obtained for 1,2-disubstituted and 1,2,3-trisubstituted aziridines. For the later aziridines ring closure and ring opening occurred at different carbon stereocenters, thus yielding products with two inverted configurations, compared to the starting amino alcohol. The 1,2-disubstituted aziridines produced azido amines of the same configuration as the starting β-amino alcohols. To obtain a complete series of diastereomeric vic-diamines, we converted the amino alcohols into cyclic sulfamidates, which reacted with sodium azide in SN2 reaction (25–58% overall yield). The azides obtained either way underwent the Staudinger reduction, giving a series of six new chiral vic-diamines of defined stereochemistries.

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Section: Synthesis Of Azidesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Regioselective and Stereodivergent Synthesis of Enantiomerically Pure Vic-Diamines from Chiral β-Amino Alcohols with 2-Pyridyl and 6-(2,2′-Bipyridyl) Moieties

2020

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“…Cinchonine found its application as an antimalarial drug as well (3), but most frequently it is applied for the treatment of gastrointestinal tract-born infections such as schistosomiasis, amebiasis, dysentery, etc. (4). The possible application of Cin for the treatment of malaria lies in its lower toxicity compared to that of quinine and a higher potency toward the parasite relative to other quininerelated compounds (5).…”

Section: Introductionmentioning

confidence: 99%

Effects of cinchonine, a Cinchona bark alkaloid, on spontaneous and induced rat ileum contractions

Ranković¹,

Stanković²,

Živković³

et al. 2019

BLL

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AIM: Quinine, a frequently used anti-malaria alkaloid isolated from the Cinchona bark, possesses numerous toxic properties, the majority of which arrive from a dysfunction of the gastrointestinal tract. Similarly, cinchonine, another alkaloid from the Cinchona bark, displays a great potential for treating malaria (especially the resistant forms). METHODS: In this work, we aimed to evaluate the effects of cinchonine on spontaneous and induced Wistar rat ileum contractions in order to uncover potential side effects that might arise after its application. RESULTS: Cinchonine produced a concentration-dependent spasmolytic activity, which was found to be reversible (i.e. disappeared after tissue wash-up), with an IC 50 value of 273 μM. Furthermore, the mechanism of action of cinchonine at IC 50 elucidated through experiments with acetylcholine and Ca 2+ -induced ileum contractions. The applied IC 50 concentration of cinchonine statistically signifi cantly prevented the occurrence of contractions after the application of specifi c agonist. The obtained results are in a range with the effects seen with standard receptor antagonists, i.e. atropine and verapamil. CONCLUSIONS: The obtained results showed that cinchonine inhibited both types of induced contractions, suggesting a Ca 2+ -channels mediated modus operandi (Fig. 4, Ref. 19). Text in PDF www.elis.sk.

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“…In vitro cytotoxicity of MON towards immunotoxins and its beneficial role in overcoming MDR has also been documented (20). members constitute a unique class of natural products used for centuries in medicine for the treatment of malaria or more recently as antiarrhythmic agents (21). Major Cinchona alkaloids have no valuable anticancer activity, for example IC 50 of quinine and quinidine for MCF-7 line in vitro was determined as 40 and 113 lM, respectively (22).…”

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confidence: 99%

Antiproliferative Activity of Polyether Antibiotic – Cinchona Alkaloid Conjugates Obtained via Click Chemistry

et al. 2015

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A series of eight new conjugates of salinomycin or monensin and Cinchona alkaloids were obtained by the Cu(I)-catalysed 1,3-dipolar Huisgen cycloaddition (click chemistry) of respective N-propargyl amides of salinomycin or monensin with four different Cinchona alkaloid derived azides. In vitro antiproliferative activity of these conjugates evaluated against three cancer cell lines (LoVo, LoVo/DX, HepG2) showed that four of the compounds exhibited high antiproliferative activity (IC50 below 3.00 μm) and appeared to be less toxic and more selective against normal cells than two standard anticancer drugs.

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Chemistry and Biology of Cinchona Alkaloids

Cited by 51 publications

References 230 publications

Regioselective and Stereodivergent Synthesis of Enantiomerically Pure Vic-Diamines from Chiral β-Amino Alcohols with 2-Pyridyl and 6-(2,2′-Bipyridyl) Moieties

Regioselective and Stereodivergent Synthesis of Enantiomerically Pure Vic-Diamines from Chiral β-Amino Alcohols with 2-Pyridyl and 6-(2,2′-Bipyridyl) Moieties

Effects of cinchonine, a Cinchona bark alkaloid, on spontaneous and induced rat ileum contractions

Antiproliferative Activity of Polyether Antibiotic – Cinchona Alkaloid Conjugates Obtained via Click Chemistry

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