Novel Macrocyclic Derivatives of Diterpenoid Isosteviol

Andreeva, O. V.; Strobykina, I. Yu.; Kataeva, О. N.; Dobrynin, A. B.; Babaev, Vasily M.; Ризванов, И. Х.; Islamov, Daut R.; Катаев, В. Е.

doi:10.6060/mhc131056k

Cited by 12 publications

(5 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We previously synthesized open-chain dinuclear isosteviol derivatives in which two ent-beyerane moieties were connected by polymethylene spacers with terminal esters via the reactions of isosteviol chloride with diols and of 16-dihydroisosteviol (8) with dibasic carboxylic acid chlorides [3,4]. Recently, two of these dinuclear derivatives, i.e., diacids 11 and 12, were transformed into dinuclear macrocycles in which two isosteviol ent-beyerane moieties were connected by diester spacers of different polymethylene chain lengths via reactions with diol ditosylates [5]. Herein we report the synthesis of analogs of the aforementioned isosteviol derivatives in which the polymethylene spacers were replaced by polyethyleneglycol (PEG) spacers.…”

mentioning

confidence: 99%

Open-Chain and Macrocyclic Polyethyleneglycol Esters of the Diterpenoid Isosteviol

et al. 2014

View full text Add to dashboard Cite

in which two isosteviol molecules were connected by polyethyleneglycol spacers were synthesized for the first time.The number of publications on chemical transformations of the ent-beyerane diterpenoid isosteviol (1, 16-oxo-entbeyeran-19-oic acid), which is obtained by acid hydrolysis of Stevia rebaudiana glycosides, has risen dramatically during the last five years [1]. Greater than 150 isosteviol derivatives have been reported [2]. We previously synthesized open-chain dinuclear isosteviol derivatives in which two ent-beyerane moieties were connected by polymethylene spacers with terminal esters via the reactions of isosteviol chloride with diols and of 16-dihydroisosteviol (8) with dibasic carboxylic acid chlorides [3,4]. Recently, two of these dinuclear derivatives, i.e., diacids 11 and 12, were transformed into dinuclear macrocycles in which two isosteviol ent-beyerane moieties were connected by diester spacers of different polymethylene chain lengths via reactions with diol ditosylates [5].

show abstract

mentioning

confidence: 99%

Open-Chain and Macrocyclic Polyethyleneglycol Esters of the Diterpenoid Isosteviol

et al. 2014

View full text Add to dashboard Cite

show abstract

“…For this, diacid 11 that was obtained by the published method [16,17] was reacted with ethyleneglycol to afford diol 12 in 98% yield (Scheme 3). Diol 12 did not react with 6 under the same conditions that were used to prepare 10.…”

mentioning

confidence: 99%

First Conjugates of the Diterpenoid Isosteviol and Glucuronic Acid

et al. 2014

View full text Add to dashboard Cite

Conjugates of the diterpenoid isosteviol (16-oxo-ent-beyeran-19-oic acid) and glucuronic acid containing two diterpenoid (ent-beyerane) skeletons joined by a 1,6-hexanedicarboxylate spacer and E-D-glucopyranuronoyl moieties were synthesized for the first time.Glucuronic acid is produced by UDP-glucuronyltransferase and is involved in the metabolism of xenobiotics (including active drug forms) to convert them into water-soluble glucuronides (glucuronosides) [1]. This is responsible for the continuously increasing interest in glucuronides of various biologically active compounds in order to increase their bioavailability and to decrease the general toxicity. Several hundred O-, N-, S-, and C-glucuronides have now been synthesized and studied [2][3][4]. However, much less attention has been paid to the carboxylate derivatives. Less than 30 amides of glucuronic acid (glucuronamides) were reported. They included branched glycopeptidomimetics [5], glycolipids [6][7][8] including anionic surfactants that transported hydrophilic drugs through hydrophobic cell membranes [7], oligosaccharides [9], conjugates with chlorin and bacteriochlorin [10], and receptors of chiral carboxylate anions [11]. Esterification (as a rule, by methyl, allyl, and benzyl alcohols) of glucuronic acid is used only to protect the carboxylic acid during glucuronide synthesis [2][3][4]. Herein we report the first synthesis of more complicated glucuronates that are conjugates of glucuronic acid with the diterpenoid isosteviol (16-oxo-ent-beyeran-19-oic acid) (1).

show abstract

“…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.…”

mentioning

confidence: 99%

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

et al. 2015

View full text Add to dashboard Cite

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...

show abstract

Novel Macrocyclic Derivatives of Diterpenoid Isosteviol

Cited by 12 publications

References 5 publications

Open-Chain and Macrocyclic Polyethyleneglycol Esters of the Diterpenoid Isosteviol

Open-Chain and Macrocyclic Polyethyleneglycol Esters of the Diterpenoid Isosteviol

First Conjugates of the Diterpenoid Isosteviol and Glucuronic Acid

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

Contact Info

Product

Resources

About