New synthesis of diterpenoid (16S)-dihydrosteviol

Khaibullin, R. N.; Strobykina, I. Yu.; Катаев, В. Е.; Лодочникова, О. А.; Gubaidullin, А. Т.; Мусин, Р. З.

doi:10.1134/s107036320905017x

Cited by 31 publications

(25 citation statements)

References 17 publications

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“…Besides, by-products of monosubstitution were formed in both cases. The reaction of bromide 4 with diterpenoid diol 10 has afforded glycoside 16 which was observed only in the MALDI spectrum that demonstrated the peak of molecular ion [M+Na] + (m/z = 1436.4) corresponding to the molecular formulae of glycoside 16 (C 73 H 112 Cl 3 NO 19 ). The reaction of bromide 4 with diterpenoid diol 11 has provided glycoside 17 isolated by a flash chromatography in 9 % yield (Scheme 2).…”

Section: Resultsmentioning

confidence: 99%

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Last Step towards Macrocyclic Glycoterpenoids Having Isosteviol and Glucosamine Moieties

Garifullin¹,

Strobykina²,

Sharipova³

et al. 2016

MHC

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Section: Resultsmentioning

confidence: 99%

“…Isosteviol 5, diterpenoid diols 10, 11, diterpenoid diacids 12, 13 were prepared according to the literature. [7,19] 3,4,6-Tri-О-acetyl-2-deoxy-2-[(2,2,2-trichloroethoxy)carbonylamino]-a-D-glucopyranosyl bromide 4 was prepared according to the literature. [20] The physicochemical properties of these compounds agreed with those published.…”

Section: Generalmentioning

confidence: 99%

Last Step towards Macrocyclic Glycoterpenoids Having Isosteviol and Glucosamine Moieties

Garifullin¹,

Strobykina²,

Sharipova³

et al. 2016

MHC

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“…The completeness of reactions and purity of products were monitored by TLC on Silufol UV-254 plates. Isosteviol (1) and its acid chloride (4) were prepared by the literature methods [21,22].…”

Section: Methodsmentioning

confidence: 99%

Synthesis and antituberculosis activity of derivatives of the diterpenoid isosteviol with azine, hydrazide, and hydrazone moieties

et al. 2011

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Derivatives of the diterpenoid isosteviol (16-oxo-ent-beyeran-19-oic acid) with azine, hydrazone, and hydrazide moieties were synthesized. They exhibited high tuberculostatic activity in vitro against the strain Mycobacterium tuberculosis H 37 R V (minimum inhibiting concentration in the range 6.3-1.7 Pg/mL).Only streptomycin, capreomycin, and kanamycin of all drugs used today for tuberculosis chemotherapy are isolated from natural sources [1]. All other tuberculosis drugs [1] and agents undergoing preclinical and clinical trials [2, 3] are products from organic syntheses. Nevertheless, over 50 metabolites of various structures that inhibit the growth of Mycobacterium tuberculosis in the range of minimum inhibiting concentrations (MIC) 60-3 Pg/mL have currently been isolated from natural plant sources [4][5][6][7][8][9][10][11][12][13][14][15][16][17]. Diterpenoids [4,5,[8][9][10][11][12][13] and triterpenoids [4,5,11,[14][15][16][17] are most widely represented among them. The diterpenoid isosteviol (16-oxo-ent-beyeran-19-oic acid) (1) also exhibits moderate antituberculosis activity (MIC = 50 Pg/mL). Our group has investigated for several years chemical modification of 1 and its derivatives in which two isosteviol molecules are linked by a polymethylene spacer with C 16 atoms [18]. It was found that the length of the spacer affects considerably the activity. Increasing the number of methylenes in the spacer from one to eight decreases MIC from 25 to 12.5 Pg/mL [18]. These results were unusual because 1, its bis-derivatives [18], and the aforementioned di-and triterpenoids of different structures [4,5,[8][9][10][11][12][13][14][15][16][17] are not nitrogenous organic compounds yet they exhibit antituberculosis activity at the level of the N-containing antituberculosis drug pyrazinamide (MIC = 12.5 Pg/mL) [19,20]. This is probably evidence that they have a different mechanism of M. tuberculosis growth inhibition. It seemed interesting to determine how the introduction of pharmacophoric N-containing moieties (hydrazide and hydrazone) into 1 and its bis-derivatives [18] affects their antituberculosis activity.For this we reacted 1 and its acid chloride 4 with hydrazine hydrate and adipic acid hydrazide (Scheme 1) and studied the ability of the resulting products to inhibit the growth of M. tuberculosis.The reaction of 1 and an excess of hydrazine hydrate in MeOH gave not isosteviol hydrazone (3) but the azine 2, which was isolated as the salt (Scheme 1). The reason for this was probably that hydrazone 3 formed and reacted with both starting 1 and that formed via hydrolysis of 3. Compound 3 was obtained pure via reaction of 1 with a 10-fold excess of anhydrous hydrazine.The reaction of isosteviol acid chloride 4 with anhydrous hydrazine in CCl 4 produced 5. Its PMR spectrum showed characteristic resonances for protons of the ent-beyerane skeleton in addition to a broad singlet of the hydrazide amine at 3.83 ppm, a broad singlet of the hydrazone amine at 4.75, and a singlet of the hydrazide amide at 6.9. The reactio...

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“…Isosteviol (1) was synthesized by the literature method [22] from Sweta sweetener (Stevian Biotechnology Corp.), mp 235°C (lit. mp 234-235°C [22] and 231-234°C [23]).…”

Section: Methodsmentioning

confidence: 99%

Synthesis of macrocycles with one and more ent-beyerane skeletons based on the diterpenoid isosteviol

et al. 2011

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Macrocycles with one and more ent-beyerane skeletons were prepared by the reaction of 16,19-dihydroxyent-beyerane with several dibasic carboxylic acid chlorides. The structures of the synthesized compounds, namely, the number of ent-beyerane skeletons in the macrocycle, depended on the length of the polymethylene chain in the acid chloride. The molecular structures of two of the synthesized macrocycles were established by x-ray crystal structures.The number of publications on the synthesis of macrocyclic compounds has risen dramatically in the last 20 years. The interest in them is due to their ability to act as host molecules, often exhibiting highly selective molecular recognition of guests (ions) [1-3]. Native macrocycles isolated from plants or marine organisms were also described in the literature [4][5][6][7]. However, these compounds have little practical value despite their biological activity because they are isolated in minimal quantities from natural sources. In this respect synthetic macrocycles obtained from biologically active metabolites isolated from natural sources in tangible quantities are much more promising. Several such compounds are known, for example, synthetic macrocycles based on bile acids [8] and mono-[9, 10] and diterpenoids [11][12][13][14]. It is noteworthy that the first macrocycles containing two diterpenoid skeletons were obtained as side products from the synthesis of compounds in which two isosteviol (16-oxo-ent-beyeran-19-oic acid) diterpenoid molecules (1) were joined by diester and anhydride spacers [14]. In order to synthesize macrocycles based on this diterpenoid, we used a more rational approach, the so-called acid-chloride approach, which consisted of the reaction of fully reduced isosteviol, diol 2, with dibasic carboxylic acid chlorides. As it turned out, the structures of the products depended on that of the starting acid chloride, namely, on the length of the hydrocarbon chain between the C(O)Cl groups.The reaction of 2 (16,19-dihydroxy-ent-beyerane) with malonic acid dichloride gave in 9% yield a product with a molecular ion that corresponded to the mass of macrocycle 3. According to PMR data this macrocycle was not a pure compound but a mixture of the head-to-head 3a and head-to-tail 3b isomers. This was indicated by the presence of not a single multiplet

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New synthesis of diterpenoid (16S)-dihydrosteviol

Cited by 31 publications

References 17 publications

Last Step towards Macrocyclic Glycoterpenoids Having Isosteviol and Glucosamine Moieties

Last Step towards Macrocyclic Glycoterpenoids Having Isosteviol and Glucosamine Moieties

Synthesis and antituberculosis activity of derivatives of the diterpenoid isosteviol with azine, hydrazide, and hydrazone moieties

Synthesis of macrocycles with one and more ent-beyerane skeletons based on the diterpenoid isosteviol

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