Biomimetic synthesis and HPLC–ECD analysis of the isomers of dracocephins A and B

Ilkei, Viktor; Spaits, András; Prechl, Anita; Szigetvári, Áron; Béni, Zoltán; Dékány, Miklós; Szántay, Csaba; Müller, Judit; Könczöl, Árpád; Szappanos, Ádám; Mándi, Attila; Antus, Sándor; Martins, Ana; Hunyadi, Attila; Balogh, György Tibor; Kalaus, György; Bölcskei, Hedvig; Hazai, László; Kurtán, Tibor

doi:10.3762/bjoc.12.247

Cited by 10 publications

(5 citation statements)

References 18 publications

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“…Best agreements were achieved for the CAM‐B3LYP PCM and the B3LYP in vacuo conformers, while the B97D PCM calculations gave the worst agreement with the BH&HLYP and CAM‐B3LYP functionals which were found the best for 4 . This result further supports the importance of the parallel application of various DFT functionals for both the geometry optimization and the ECD calculation steps …”

Section: Resultssupporting

confidence: 73%

“…13,27,31 Acetylcholinesterase inhibitory activity of the products was tested, and rac-7 was found to show moderate AChE inhibitory activity with 35.4% inhibition at 40-μM concentration. The neuroprotective activities of the products were also tested against hydrogen peroxide (H 2 O 2 ), β-amyloid-25-35 fragment (Aβ [25][26][27][28][29][30][31][32][33][34][35] ), and oxygen-glucose deprivation-induced neurotoxicity in human neuroblastoma SH-SY5Y cells. The preliminary screenings showed that rac-3 at 1-μM concentration displayed neuroprotective activity against oxygen-glucose deprivation-induced cellular injuries in human neuroblastoma SH-SY5Y cells with 18.6% increase in cell viability.…”

Section: Computational Sectionmentioning

confidence: 99%

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HPLC‐ECD and TDDFT‐ECD study of hexahydropyrrolo[1,2‐a]quinoline derivatives

et al. 2018

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Synthesis of racemic hexahydropyrrolo[1,2‐a]quinoline derivatives (1‐8) was performed by utilizing the Knoevenagel‐[1,5]‐hydride shift‐cyclization domino reaction. Separation of the enantiomers of the chiral products (1‐8) was carried out by chiral high‐performance liquid chromatography, and online high‐performance liquid chromatography‐electronic circular dichroism (ECD) spectra were recorded to elucidate the absolute configuration by comparing the experimental and time‐dependent density functional theory‐ECD spectra obtained at various theoretical levels. For 1 of the products, the time‐dependent density functional theory‐ECD calculations allowed determining both the relative and the absolute configuration by distinguishing the 4 stereoisomers. One of the compounds with spiro 1,3‐cyclohexanedione moiety (7) possessed moderate acetylcholinesterase inhibitory activity, while 3 showed neuroprotective activity in oxygen‐glucose deprivation‐induced neurotoxicity in human neuroblastoma SH‐SY5Y cells.

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Section: Resultssupporting

confidence: 73%

Section: Computational Sectionmentioning

confidence: 99%

HPLC‐ECD and TDDFT‐ECD study of hexahydropyrrolo[1,2‐a]quinoline derivatives

et al. 2018

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“…These derivatives were prepared by acid-catalyzed regioselective Mannich reaction in which the in situ generated N-acyliminium ion started an electrophile attack to the aromatic A ring of the corresponding flavonoid precursors. Further flavone alkaloids were also synthesized: 8-(2 -pyrrolidinon-5 -il)-quercetin (35) and (−)-epicatechin (37) with the same substituent in position eight (38) and in position six (39), respectively [42,43]. Starting from quercetin (34) compound 35 and its C-6 (36) isomer were obtained in a ratio of 94:6 ( Figure 12).…”

Section: Vindoline and Flavone Derivatives Containing 2-pyrrolidone Ringmentioning

confidence: 99%

Results in Chemistry of Natural Organic Compounds. Synthesis of New Anticancer Vinca Alkaloids and Flavone Alkaloids

et al. 2020

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The antitumor indole–indoline alkaloids of the evergreen Catharanthus roseus—namely vinblastine and vincristine—are widely used in chemotherapy of cancer. Many efforts were made to synthesize more efficient derivatives with less side-effect. The 14,15-cyclopropane derivative of vinblastine was synthesized successfully by a five-step procedure starting from vindoline. Vincristine, vinorelbine and several derivatives condensed with a cyclopropane ring were synthesized. Various hybrid molecules were prepared by the coupling reaction of vindoline and methyl ester of tryptophan, which were conjugated by carrier peptides of octaarginine. Studying the halogenation reactions of vindoline and catharanthine some fluorine derivatives were obtained which showed promising antitumor activity on various tumor types. The synthesis of the Aspidospermane alkaloid bannucine and 5′-epibannucine were carried out using N-acyliminium intermediates. The same intermediate was also applied in the first synthesis of sessiline. The research group have synthesized of flavonoid alkaloids: dracocephins A and B. Further three flavonoid alkaloids, namely 8-(2”-pyrrolidinon-5′′-yl)quercetin, 6-(2′′-pyrrolidinon-5′′-yl)-(−)- and 8-(2′′-pyrrolidinon-5′′-yl)-(−)-epicatechin were prepared by acid-catalyzed regioselective Mannich reaction starting from the corresponding flavonoid precursor. Vindoline was also coupled to synthetic pharmacophores, such as triphenylphosphine and various N-heterocycles. Some of these hybrid molecules showed significant antitumor activity. Furthermore, 7-OH and 7-NH modified flavonoid derivatives were synthesized by a regioselective alkylation followed by Smiles rearrangement and hydrolysis.

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“…In order to determine the absolute configuration of the enantiomers of 10a and 11a and correlate it with the characteristic electronic circular dichroism (ECD) transitions, the enantiomers of 10a and 11a were separated by chiral HPLC using Chiralpack IC stationary phase and online HPLC-ECD spectra of the separated enantiomers were recorded. HPLC-ECD measurements aided with time-dependent density functional theory electronic circular dichroism (TDDFT-ECD) calculations represent an efficient method to study the enantiomers in scalemic or racemic mixtures of natural [36,37] or synthetic derivatives [38,39]. The solution TDDFT-ECD approach [40] was applied to determine the absolute configuration of the separated enantiomers by comparing the experimental HPLC-ECD spectra with the computed ones.…”

Section: -Hydride Shift-cyclization Domino Reactionmentioning

confidence: 99%

[1,5]-Hydride Shift-Cyclization versus C(sp2)-H Functionalization in the Knoevenagel-Cyclization Domino Reactions of 1,4- and 1,5-Benzoxazepines

et al. 2020

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Domino cyclization reactions of N-aryl-1,4- and 1,5-benzoxazepine derivatives involving [1,5]-hydride shift or C(sp2)-H functionalization were investigated. Neuroprotective and acetylcholinesterase activities of the products were studied. Domino Knoevenagel-[1,5]-hydride shift-cyclization reaction of N-aryl-1,4-benzoxazepine derivatives with 1,3-dicarbonyl reagents having active methylene group afforded the 1,2,8,9-tetrahydro-7bH-quinolino [1,2-d][1,4]benzoxazepine scaffold with different substitution pattern. The C(sp3)-H activation step of the tertiary amine moiety occurred with complete regioselectivity and the 6-endo cyclization took place in a complete diastereoselective manner. In two cases, the enantiomers of the chiral condensed new 1,4-benzoxazepine systems were separated by chiral HPLC, HPLC-ECD spectra were recorded, and absolute configurations were determined by time-dependent density functional theory- electronic circular dichroism (TDDFT-ECD) calculations. In contrast, the analogue reaction of the regioisomeric N-aryl-1,5-benzoxazepine derivative did not follow the above mechanism but instead the Knoevenagel intermediate reacted in an SEAr reaction [C(sp2)-H functionalization] resulting in a condensed acridane derivative. The AChE inhibitory assays of the new derivatives revealed that the acridane derivative had a 6.98 μM IC50 value.

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Biomimetic synthesis and HPLC–ECD analysis of the isomers of dracocephins A and B

Cited by 10 publications

References 18 publications

HPLC‐ECD and TDDFT‐ECD study of hexahydropyrrolo[1,2‐a]quinoline derivatives

HPLC‐ECD and TDDFT‐ECD study of hexahydropyrrolo[1,2‐a]quinoline derivatives

Results in Chemistry of Natural Organic Compounds. Synthesis of New Anticancer Vinca Alkaloids and Flavone Alkaloids

[1,5]-Hydride Shift-Cyclization versus C(sp2)-H Functionalization in the Knoevenagel-Cyclization Domino Reactions of 1,4- and 1,5-Benzoxazepines

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