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Джалмаханбетова, Р. И.; Suleimen, E. M.; Рахимова, Б. Б.; Talzhanov, N. A.; Kulyyasov, A. T.; Адекенов, С. М.

doi:10.1023/a:1022630603323

Cited by 5 publications

(3 citation statements)

References 2 publications

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“…Starting lactone 1, mp 100-102°C, was isolated from the aerial part of Artemisia filatovae Kupr. [9]. Elemental analysis of 1 agreed with that calculated.…”

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confidence: 73%

Synthesis and molecular structure of halohydrins of the guaianolide ludartin

et al. 2010

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Chloro-and bromhydrin derivatives of the sesquiterpene lactone ludartin were synthesized for the first time. Their structures were established by spectral data and an x-ray structure analysis.Compounds containing a halohydrin moiety were observed in natural biologically active compounds including sesquiterpene lactones [1][2][3]. Halogenated compounds, many of which exhibit antitumor, cytotoxic, and antifungal activity, are of special interest among the numerous synthetic derivatives of sesquiterpene lactones [4][5][6][7].The goal of our work was to synthesize halohydrin derivatives of the guaianolide ludartin (1).Reaction of 1 with LiCl in the presence of CH 3 CO 2 H formed a mixture of products. Separation by column chromatography over silica gel isolated two crystalline compounds 2 and 3 with mp 148 (dec.) and 188-190°C, respectively.The IR spectra of 2 and 3 exhibited absorption bands characteristic of hydroxyls. The PMR spectrum of 2 gave a resonance at G H 1.30 ppm as a singlet that was characteristic of a methyl on C-4 and a resonance as a doublet of doublets at G H 4.15 ppm with SSCC 8.0 and 11.0 Hz that was assigned to a geminal proton on C-3 (Table 1). The resonance for the C-4 methyl in derivative 3 was shifted strongly to weak field compared with that of 2. Such a shift of the resonance (by ~0.57 ppm) confirmed that a Cl atom was in a position geminal to the methyl. The resonance for the C-3 proton was present as a doublet at G H 4.12 ppm with SSCC 4.0 Hz. The resonance for C-4 in the 13 C NMR spectrum of 2 was shifted strongly to weak field by 14 ppm and appeared as a singlet at G C 80.56 ppm because of the influence of the hydroxyl. The resonance of this C atom in the other derivative 3 appeared also in this same region at G C 80.48 ppm whereas the resonance for C-3 was shifted strongly to weak field by ~27 ppm and appeared as a doublet with G C 79.85 ppm. These spectral data confirmed that the epoxide ring opened in 1 from two sides. The location and configuration of the hydroxyl and Cl atom in 2 and 3 were confirmed by an x-ray structure analysis (XSA). Figure 1 shows the molecular structures of 2 and 3. The bond lengths in the molecules were normal. The conformations of corresponding rings in 2 and 3 were the same. The five-membered rings had the twist conformation with atoms C3 and C4 deviating by -0.335 and 0.379 in 2 and -0.374 and 0.228 A° in 3. Atoms C6 and C7 also deviated (0.177 and -0.240 in 2; 0.205 and -0.354 A° in 3) from the planes of the remaining atoms. The seven-membered ring had the usual chair conformation. These same ring conformations were observed in the crystal structure of the related compound micheliolide (4) [8].

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“…Starting lactone 1, mp 100-102°C, was isolated from the aerial part of Artemisia filatovae Kupr. [9]. Elemental analysis of 1 agreed with that calculated.…”

supporting

confidence: 73%

Synthesis and molecular structure of halohydrins of the guaianolide ludartin

et al. 2010

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“…Compounds that are analogs of natural phosphates are attracting great attention, since they, as a rule, are chemically more stable than the phosphates themselves and, therefore, may have a prolonged action [ 33 ]. In terms of the synthesis of new phosphorus-containing analogs of natural phosphates, potentially possessing high biological activity, dialkylphosphonate derivatives of arteannuin B, grossheimin, were obtained by a method similar to the synthesis of phosphorus derivatives of arglabin [ 34 , 35 , 36 ].…”

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confidence: 99%

“…In continuation of the synthesis of estafiatin derivatives, interaction with dimethyl-, diethyl-, dipropyl-, and dibutylphosphites was considered under conditions similar to those described for monoterpene α-enones [ 37 ] and sesquiterpene lactone of the cadinane structure arteannuin B [ 36 ].…”

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confidence: 99%

Syntheses Based on 3,4α-Epoxy-1,5,7α,6β(H)-guai-10(14),11(13)-dien-6,12-olide

Адекенов¹

2022

Molecules

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The sesquiterpene γ-lactone estafiatin 1, the molecule of which has a structure of 3,4α-epoxy-1,5,7α,6β(H)-guai-10(14),11(13)-dien-6,12-olide, is characteristic of plants of the genera Achillea L. and Artemisia L. of the Asteraceae family. This article presents the results of chemical modification for three reaction centers of the estafiatin molecule 1: epoxy cycle, exomethylene group conjugated with γ-lactone carbonyl, and exomethylene group in position С10=С14; and at the same time 33 new derivatives were synthesized, the structures of which were established based on physicochemical constants, spectral data (IR-, PMR-, 13C-NMR), and X-ray diffraction analysis. The stereo- and regiospecificity, as well as the chemoselectivity of the reaction based on estafiatin molecule 1, are discussed. The reactivity of the substrate is significantly influenced by the stereochemistry of its molecule, the nature of the reagent, and the reaction medium. Based on the results of in silico screening, derivatives of estafiatin with high binding energies for both DNA-topoisomerase I and DNA-topoisomerase II were identified. The values of the inhibitory dose of IC50 for estafiatin 1 and its derivatives were determined on cell lines of eight types of tumors. In vivo experiments of the samples made it possible to establish that estafiatin 1 and its derivatives have pronounced antitumor activity against Pliss lymphosarcoma, Walker’s carcinosarcoma, sarcoma 45, sarcoma-180, alveolar liver cancer PC-1, leukemia P-388 and L-1210, and sarcoma-45 resistant to 5-fluorouracil.

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