Macrocyclic Derivatives of Diterpenoid Isosteviol with Hydrazide and Hydrazone Moieties

Garifullin, B. F.; Andreeva, O. V.; Strobykina, I. Yu.; Babaev, Vasily M.; Катаев, В. Е.

doi:10.6060/mhc130334k

Cited by 8 publications

(3 citation statements)

References 30 publications

(79 reference statements)

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“…One of the compounds, which was methylene lactone isosteviol analogue ( Figure 2 E), showed the most activity against HepG2 cell lines with an IC 50 value of 9l mM [ 82 , 83 ]. The functionalization of isosteviol using hydrazone moiety has proved to be effective biologically [ 84 ]. The 2,4-dinitro phenyl hydrazone (2,4-DNPH), 4-nitro phenyl hydrazone (4-NPH) are two such derivatives that have been synthesized and tested for their cytotoxic, antimalarial and anti-trypanosomal and anti-leishmaniasis activities.…”

Section: Pharmacological Activities Of Isosteviol Derivativesmentioning

confidence: 99%

Bioactivity Profile of the Diterpene Isosteviol and its Derivatives

et al. 2019

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Steviosides, rebaudiosides and their analogues constitute a major class of naturally occurring biologically active diterpene compounds. The wide spectrum of pharmacological activity of this group of compounds has developed an interest among medicinal chemists to synthesize, purify, and analyze more selective and potent isosteviol derivatives. It has potential biological applications and improves the field of medicinal chemistry by designing novel drugs with the ability to cope against resistance developing diseases. The outstanding advancement in the design and synthesis of isosteviol and its derivative has proved its effectiveness and importance in the field of medicinal chemical research. The present review is an effort to integrate recently developed novel drugs syntheses from isosteviol and potentially active pharmacological importance of the isosteviol derivatives covering the recent advances.

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Section: Pharmacological Activities Of Isosteviol Derivativesmentioning

confidence: 99%

Bioactivity Profile of the Diterpene Isosteviol and its Derivatives

et al. 2019

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“…The dihydrazide protons resonated as multiplets at 7.31-7.38 and 7.71-7.77 ppm. Like for macrocyclic isosteviol derivatives with the same fragments [3], this was apparently indicative of several hindered conformers of macrocycle 7. The anomeric protons of its glucuronates were found in the spectrum as a single doublet at 3.88 ppm with SSCC 9.51 Hz.…”

mentioning

confidence: 94%

“…In continuation of research on the synthesis of macrocyclic glycoterpenoids [2], herein we present results for the synthesis of a macrocyclic conjugate of isosteviol and glucuronic acid. We used the methodology for synthesizing macrocyclic isosteviol derivatives [3,4] in which two dihydroisosteviol molecules were first bound through the hydroxyls by reacting them with carboxylic acid chlorides. The resulting diacids (e.g., diacid 4 in Scheme 1) were converted to macrocycles by reacting their carboxylic acid chlorides with diols.…”

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confidence: 99%

Synthesis of a Macrocyclic Conjugate of the Diterpenoid Isosteviol and Glucuronic Acid

et al. 2015

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A macrocyclic conjugate of the natural diterpenoid isosteviol (16-oxo-ent-beyeran-19-oic acid) and glucuronic acid was synthesized for the first time. The conjugate contained two molecules of dihydroisosteviol E-D-glucuronoside joined by 1, 8-octanedicarboxylate and 1,8-octanedicarbazoyl spacers. We recently reported the synthesis of the first conjugate of the diterpenoid isosteviol (16-oxo-ent-beyeran-19-oic acid) and glucuronic acid [1] in which two molecules of the isosteviol derivative dihydroisosteviol (16-hydroxy-ent-beyeran-19-oic acid) functionalized at the carboxyls by E-D-glucopyranuronoyl residues were connected by a 1,6-hexanedicarboxylate spacer. In continuation of research on the synthesis of macrocyclic glycoterpenoids [2], herein we present results for the synthesis of a macrocyclic conjugate of isosteviol and glucuronic acid. We used the methodology for synthesizing macrocyclic isosteviol derivatives [3,4] in which two dihydroisosteviol molecules were first bound through the hydroxyls by reacting them with carboxylic acid chlorides. The resulting diacids (e.g., diacid 4 in Scheme 1) were converted to macrocycles by reacting their carboxylic acid chlorides with diols.The starting carbohydrate component was D-(+)-glucurono-3,6-lactone (1), which was easily converted to methyl-1,2,3,4-tetra-O-acetyl-E-D-glucopyranuronate (2) as before [5]. The methyl-1-deoxy-1-bromo-2,3,4-tri-O-acetyl-E-Dglucopyranuronate 3 that was obtained from it by the literature method [6] was then reacted with diacid 4 in refluxing CH 2 Cl 2 in the presence of tetrabutylammonium bromide (TBAB) and potash. Bisglucuronide 5 was obtained in 56% yield. Its anomeric protons appeared in the PMR spectrum as a single doublet at 5.73 ppm with vicinal SSCC 8.02 Hz. This indicated convincingly that the glycoside bonds had the E-orientation.In fact, the anomeric proton of methyl 1,2,3,4-tetra-O-acetyl-E-D-glucopyranuronate 2 resonated as a doublet at 5.73 ppm with vicinal SSCC 7.8 Hz [6] whereas the anomeric proton of the corresponding D-D-glucopyranuronate was found as a doublet at 6.34 ppm with SSCC 3.7 Hz [5]. Then, bisglucuronoside 5 was reacted at room temperature with hydrazine hydrate as before [7]. The PMR spectrum of the product, which was obtained in 90% yield, lacked the strong singlets corresponding to acetate resonances at 1.96, 1.98, and 1.99 ppm and the ester methyls of the glucopyranuronates at 3.68 ppm, which were observed in the spectrum of 5. A multiplet that was characteristic of the hydrazide NH proton appeared at 7.69-7.73 ppm. All these data combined with MALDI mass spectral data indicated that dihydrazide 6 had formed. The reaction did not affect the carbohydrate anomeric centers. Therefore, the glycoside bonds in 6 retained the E-orientation. Its glucuronate anomeric protons resonated as a single doublet at 3.78 ppm with SSCC 9.63 Hz, which agreed with the literature for various E-glycosides of non-acylated glucuronic acid methyl ester (e.g., G 4.26 ppm and 3 J = 9.4 Hz [8]) and with previous work [9] in whic...

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Synthesis of the First Macrocyclic Glycoterpenoid Based on Trehalose and the Diterpenoid Isosteviol

et al. 2015

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Macrocyclic Derivatives of Diterpenoid Isosteviol with Hydrazide and Hydrazone Moieties

Abstract: Novel macrocyclic derivatives of diterpenoid isosteviol (16-oxo-ent-beyeran-19-oic acid) possessing two or four entbeyerane skeletons bonded with linkers having ester, hydrazide, and hydrazone moieties were synthesized.

Cited by 8 publications

References 30 publications

Bioactivity Profile of the Diterpene Isosteviol and its Derivatives

Bioactivity Profile of the Diterpene Isosteviol and its Derivatives

Synthesis of a Macrocyclic Conjugate of the Diterpenoid Isosteviol and Glucuronic Acid

Synthesis of the First Macrocyclic Glycoterpenoid Based on Trehalose and the Diterpenoid Isosteviol

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