O. V. Andreeva

Synthesis and antituberculosis activity of derivatives of Stevia rebaudiana glycoside steviolbioside and diterpenoid isosteviol containing hydrazone, hydrazide, and pyridinoyl moieties

Conjugates of the antituberculosis drug isoniazid (isonicotinyl hydrazine) and isomeric hydrazides of nicotinic and α-picolinic acid with glycoside steviolbioside from the Stevia rebaudiana plant and the product of its acid hydrolysis, diterpenoid isosteviol, were synthesized. In addition, isosteviol hydrazide and hydrazone derivatives as well as conjugates containing two isosteviol moieties joined by a dihydrazide linker were obtained. The parental compounds and their synthetic derivatives were found to inhibit the in vitro growth of Mycobacterium tuberculosis (H37RV). The measured minimal concentrations of stevio-side and steviolbioside, at which the growth of M. tuberculosis was inhibited by 100% (MIC), were 7.5 and 3.8 μg/ml, respectively. MIC values for steviolbioside and isosteviol conjugates with hydrazides of pyridine carbonic acid were within the ranges of 5–10 and 10–20 μg/ml, respectively. The maximal inhibitory effect against M. tuberculosis was shown by the isosteviol conjugates with adipic acid dihydrazide (MIC 1.7 and 3.1 μg/ml). Antituberculosis activities of the tested compounds were higher than the activity of antituberculosis drug Pyrizanamide (MIC 20 μg/ml) but lower than that of antituberculosis drug isoniazid (MIC 0.02–0.04 μg/ml).

Development of synthetic approaches to macrocyclic glycoterpenoids on the basis of glucuronic acid and diterpenoid isosteviol

An approach has been developed to the synthesis of macrocyclic glycoterpenoids containing diterpenoid isosteviol and glucuronic acid fragments. Selective screening revealed compounds exhibiting antitubercular activity against H37RV, M. Avium, and M. Terrae strains at a level comparable to the known antitubercular drugs isoniazid, ofloxacin, and pyrazinamide. The compound possessing the highest antitubercular activity is non-cytotoxic toward human erythrocytes.

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

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 β-D-glucuronoside joined by 1,8-octanedicarboxylate and 1,8-octanedicarbazoyl spacers.

Synthesis and antituberculosis activity of the first macrocyclic glycoterpenoids comprising glucosamine and diterpenoid isosteviol

The first macrocyclic glycoterpenoids comprising glucosamine and diterpenoid isosteviol moieties were synthesized and evaluated for inhibition activity against Mycobacterium tuberculosis H37Rv.

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

A macrocyclic glycoterpenoid containing the diterpenoid dihydroisosteviol (16-hydroxy-ent-beyeran-19- oic acid) and α,α′-trehalose linked by an ester spacer was synthesized.

Hybrid compounds of ent-beyerane diterpenoid isosteviol with pyridinecarboxylic acid hydrazides. Synthesis, structure, and antitubercular activity

Hybrid compounds derived from natural diterpenoid isosteviol and antitubercular drug isoniazid (isonicotinic acid hydrazide) and its isomers (nicotinic and 2-picolinic acid hydrazides) were synthesized, and their structure in crystal and in solution was studied. The newly synthesized compounds were found to inhibit Micobacterium tuberculosis (H37RV strain) in vitro, the minimal inhibitory concentration being 10–20 μg/ml.

Macrocyclic derivatives of steviolbioside, a glycoside isolated from Stevia Rebaudiana

Macrocycles consisting of two or four steviolbioside (S. Rebaudiana glycoside) fragments linked at the carboxy groups by an octamethylene chain and at the 16-positions by alkanedihydrazide spacer derived from adipic, suberic, or sebacic acid have been synthesized.

First Conjugates of the Diterpenoid Isosteviol and Glucuronic Acid

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 β-D-glucopyranuronoyl moieties were synthesized for the first time.

Chemistry and Structure of Diterpene Compounds of the Kaurane Series: VII. Chiral Complexes of Isosteviol with Aromatic Compounds

Abstract(4α,8β,13β)-13-Methyl-16-oxo-17-norkaurane-18-carboxylic acid (isosteviol) forms with aniline, dimethylaniline, and toluene individual 2:1 molecular complexes whose crystals are isostructural. According to X-ray diffraction data, the supramolecular crystal structure of these complexes is formed by chiral double helices with a 43 screw axis, consisting of isosteviol molecules. The strands of the helices are linked together by intermolecular hydrogen bonds involving the carboxy and carbonyl groups of two isosteviol molecules of neighboring helices. In their turn, the two hydrogen-bonded isosteviol molecules form head-to-tail pseudocage dimers. The aromatic guests occupy fairly large cavities between the strands of isosteviol helices.

Synthesis of macrocycles on the basis of diterpenoid isosteviol and trehalose

Macrocyclic glycoterpenoids containing trehalose and isosteviol fragments have been synthesized. Selective screening has revealed compounds exhibiting antitubercular activity against H37RV, M. Avium and M. Terrae at a level comparable to the known antitubercular drugs isoniazid, ofloxacin, and pyrazinamide.