B. F. Garifullin

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).

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.

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

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 establishedby x-ray crystal structures.

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.

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

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 H37RV (minimum inhibiting concentration in the range 6.3–1.7 μg/mL).

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.

Synthetic glycosides containing two isosteviol fragments functionalized with D-glucopyranose

The synthesis of isosteviol (16-oxo-ent-beyeran-19-oic acid) glycosides in which two isosteviol fragments functionalized with tetra-O-acetyl-D-glucopyranose are linked through a diester spacer is described for the first time.

Functionalization of the double bond in the glycoside of the Stevia rebaudiana plant steviolbioside, as a way to macrocyclic glycosides

The C16=C17 bond in the glycoside steviolbioside from the plant Stevia rebaudiana was oxidized for the first time. Ketone, thiosemicarbazone, and oxime of steviolbioside with a heptaacetylated sophorosyl fragment, as well as binuclear and tetranuclear macrocyclic derivatives of this rebaudioside were synthesized.