Study of alkaloids of the Siberian and Altai flora. 10. Synthesis of N(20)-deethyllappaconitine derivatives

Pankrushina, N. A.; Nikitina, I. A.; Anferova, N. V.; Osadchii, S. A.; Шакиров, М. М.; Шульц, Э. Э.; Толстиков, Г. А.

doi:10.1023/b:rucb.0000012375.59390.38

Cited by 14 publications

(10 citation statements)

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“…NMR signal assignments were carried out with the aid of a combination of 1D and 2D NMR techniques that included Heteronuclear Single Quantum Correlation (HSQC) and Heteronuclear Multiple Bond Correlation (HMBC). Signals in the NMR 1 H and 13 C spectra of the lappaconitine part of new compounds were assigned by correlation with those of lappaconitine 1 [53]. Copies of NMR 1 H and 13 C spectra of all new compounds a given in Supplementary file.…”

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confidence: 99%

Hybrides of Alkaloid Lappaconitine with Pyrimidine Motif on the Anthranilic Acid Moiety: Design, Synthesis, and Investigation of Antinociceptive Potency

et al. 2020

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Convenient and efficient routes to construct hybrid molecules containing diterpene alkaloid lappaconitine and pyrimidine fragments are reported. One route takes place via first converting of lappaconitine to 1-ethynyl-lappaconitine, followed by the Sonogashira cross-coupling-cyclocondensation sequences. The other involves the palladium-catalyzed carbonylative Sonogashira reaction of 5′-iodolappaconitine with aryl acetylene and Mo (CO)6 as the CO source in acetonitrile and subsequent cyclocondensation reaction of the generated alkynone with amidines. The reaction proceeded cleanly in the presence of the PdCl2-(1-Ad)2PBn∙HBr catalytic system. The protocol provides mild reaction conditions, high yields, and high atom and step-economy. Pharmacological screening of lappaconitine-pyrimidine hybrids for antinociceptive activity in vivo revealed that these compounds possessed high activity in experimental pain models, which was dependent on the nature of the substituent in the 2 and 6 positions of the pyrimidine nucleus. Docking studies were undertaken to gain insight into the possible binding mode of these compounds with the voltage-gated sodium channel 1.7. The moderate toxicity of the leading compound 12 (50% lethal dose (LD50) value was more than 600 mg/kg in vivo) and cytotoxicity to cancer cell lines in vitro encouraged the further design of therapeutically relevant analogues based on this novel type of lappaconitine–pyrimidine hybrids.

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Section: General Informationmentioning

confidence: 99%

Hybrides of Alkaloid Lappaconitine with Pyrimidine Motif on the Anthranilic Acid Moiety: Design, Synthesis, and Investigation of Antinociceptive Potency

et al. 2020

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“…14, 15 The modification of the nitro gen containing substituent in the aromatic moiety of the lappaconitine molecule was also described in the litera ture. 1, 16 The replacement of the nitrogen containing sub stituent in the aromatic ring with an unsaturated frag ment 17 and oxidative bromination of compound 1 with a mixture of Br 2 , NaIO 4 , and AcOH giving rise to N deethyl 5´ bromolappaconitine 18 were performed.…”

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Study of alkaloids of the Siberian and Altai flora

et al. 2006

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“…Lappaconitine N(20)-oxide II and N(20)-deethyllappaconitine III were synthesized earlier in usual way with using solvents [18,19]. We now report the oxidation of lappaconitine I by the direct reaction of I and 3-Cl-perbenzoic acid (3-Cl-PBA) as well as the N(20)-deethylation of lappaconitine I by the interaction of I and N-bromosuccinimide (NBS) achieved under solvent-free conditions according to the reactions scheme (Fig.…”

Section: Mechanochemical Synthesis Of Lappaconitine Derivativesmentioning

confidence: 99%

“…To prevent abrasive impurities from vial walls and balls during the milling process, it was necessary to carry out a lining of them. The reaction mixtures were monitored by TLC and HPLC using as outside standard samples of lappaconitine I and compounds II, III obtained by the methods described [18,19]. N-Acetylanthranilic moiety is the chromofore in the lappaconitine molecule.…”

Section: Mechanochemical Synthesis Of Lappaconitine Derivativesmentioning

confidence: 99%

Solvent-Free Mechanochemical Modification of Lappaconitine and Piroxicam

Pankrushina

Nikitina

Chernjak

et al. 2008

Materials and Manufacturing Processes

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A mechanochemical procedure of ball milling was applied to a solvent-free synthesis of natural alkaloid lappaconitine derivatives. A mixture of purely solid lappaconitine and 3-Cl-perbenzoic acid reacted to give lappaconitine N(20)-oxide with a good isolated yield (57% after workup). The ball milling of solid lappaconitine and N-bromosuccinimide affords N(20)-deethyllappaconitine with an acceptable (42%) yield. The mechanochemical approach was also applied for acylation of the anti-inflammatory drug piroxicam to improve its therapeutical properties. Consequently piroxicam 4-nitrobenzoate was obtained under the solvent-free reaction conditions with a moderate yield as a result of mechanical activation of the reaction between piroxicam and 4-nitrobenzoyl chloride in the presence of the aluminum oxide impregnated with thriethylamine. The reaction mixtures were analyzed after ball milling by HPLC in the proposed conditions.

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Study of alkaloids of the Siberian and Altai flora. 10. Synthesis of N(20)-deethyllappaconitine derivatives

Cited by 14 publications

References 6 publications

Hybrides of Alkaloid Lappaconitine with Pyrimidine Motif on the Anthranilic Acid Moiety: Design, Synthesis, and Investigation of Antinociceptive Potency

Hybrides of Alkaloid Lappaconitine with Pyrimidine Motif on the Anthranilic Acid Moiety: Design, Synthesis, and Investigation of Antinociceptive Potency

Study of alkaloids of the Siberian and Altai flora

Solvent-Free Mechanochemical Modification of Lappaconitine and Piroxicam

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