Diterpenoid Isosteviol Research Articles

Open-Chain and Macrocyclic Polyethyleneglycol Esters of the Diterpenoid Isosteviol

Open-chain and macrocyclic derivatives of the diterpenoid isosteviol (16-oxo-ent-beyeran-19-oic acid) in which two isosteviol molecules were connected by polyethyleneglycol spacers were synthesized for the first time.

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.

Metal derivatives of diterpenoid isosteviol

Metal salts (including transition metals salts) of chiral natural diterpenoid isosteviol and its hydrophosphoryl derivative were obtained for the first time. The compounds obtained can be used in pharmaceutics, metal catalysis, and also for creating new materials with magnetic properties.

Investigation of diterpenoid isosteviol ammonium derivatives by matrix-assisted laser desorption/ionization mass spectrometry

Matrix-assisted laser desorption/ionization (MALDI) mass spectra of diterpenoid isosteviol ammonium derivatives have been analyzed. The compounds were synthesized as antibacterial agents. It has been found that peaks of salt cations were detected in positive ion MALDI mass spectra of mono-quaternary derivatives. The fragmentation of bis-quaternary salts depended on the distance between the ammonium centers. Clusters containing dication and acidic matrix anion have been observed for compounds with two quaternized nitrogen atoms connected by a nonanomethylene or a longer spacer. Similar clusters did not form for compounds containing pentamethylene or a shorter spacer between two quaternized nitrogen atoms.

Synthesis of Macrocyclic Derivatives of the Diterpenoid Isosteviol with Two and Four ent-Beyerane Frameworks

Macrocycles with two or four ent-beyerane diterpenoid frameworks joined by ester spacers with various polymethylene chain lengths (n = 2, 6, 8) were synthesized for the first time from the diterpenoid isosteviol (16-oxo-ent-beyeran-19-oic acid).

Synthesis, structures, and properties of 15-oxoisosteviol thiosemicarbazone and oxime

New nitrogen-containing derivatives of the diterpenoid isosteviol (16-oxo-ent-beyeran-19-oic acid) containing oxo, hydroxyimine, and thiosemicarbazone groups were synthesized. Isosteviol 15-oxo-16-thiosemicarbazone forms a 1: 1 complex with CuII and inhibits the growth of Mycobacterium tuberculosis (H37RV, in vitro) at the minimum inhibitory concentration of 20 μg mL−1.

Macrocyclic Derivatives of Diterpenoid Isosteviol with Hydrazide and Hydrazone Moieties

Among about 3000 macrocyclic compounds* isolated from various natural sources (macrolactames, macrolides, cyclic peptides, cyclic oligosaccharides etc.) about 100 compounds are macrocyclic diterpenoids.[1-3] The most famous are cembranes, jatrophanes, lathyranes; on the contrary, casbanes and dolabellanes are rather rare in nature.[1,3-7] Their carbohydrogen skeleton is 14-, 12, or 11membered cycle fused with cyclopropane, cyclopentane[1,3,6] or oxirane[7] rings. It should be emphasized that each naturally occurring macrocyclic diterpenoid is a one molecule (Scheme 1a). The literature has provided no examples of naturally

Novel Macrocyclic Derivatives of Diterpenoid Isosteviol

Novel Macrocyclic Derivatives of Diterpenoid Isosteviol

Synthesis and antituberculosis activity of conjugates of the diterpenoid isosteviol and the drug dimephosphon

Conjugates of the diterpenoid isosteviol (16-oxo-ent-beyeran-19-oic acid) and the drug dimephosphon (1,1dimethyl-3-oxobutylphosphonic acid dimethyl ester) were synthesized. They inhibited completely growth of M. tuberculosis (H37Rv, in vitro) with MIC values of 5–10 μg/mL (MIC value of the antituberculosis drug isoniazid in a control was 0.5 μg/mL).

Ethylent-15α-[(2-nitrobenzyloxy)methyl]-16-oxobeyeran-20-oate

In the title compound, C30H41NO6, the three six-membered rings adopt chair conformations and the stereochemistry of the A/B and B/C ring junctions are trans. The five-membered ring D adopts an envelope conformation, with the methyl­ene C atom as the flap. The title compound was synthesized via esterification, Tollens reaction, 1,5-hydride shift from the natural tetracyclic diterpenoid isosteviol

Synthesis and antimicrobial activity of several bis-quaternized ammonium derivatives of the diterpenoid isosteviol

Previously unreported bis-quaternized ammonium derivatives of the diterpenoid isosteviol (16-oxo-entbeyeran-19-oic acid) were synthesized. The compound in which the two quaternized N atoms were joined by a dodecamethylene spacer had the greatest antimicrobial activity and was comparable in activity with ciprofloxacin and clotrimazole.

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.

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

Conjugates of antitubercular drug Isoniazid (hydrazide of isonicotinic acid), nicotinic and alpha-picolinic acid hydrazides and glycoside steviolbioside from the plant Stevia rebaudiana as well as the product of its acid hydrolysis, diterpenoid isosteviol, were synthesized. Besides, isosteviol hydrazide and hydrazone derivatives as well as conjugates containing two isosteviol moieties connected by dihydrazide linker were also obtained. Both initial compounds and their synthetic derivatives inhibit the growth of Mycobacterium tuberculosis (H37Rv in vitro). The minimum concentration at which the growth of M. tuberculosis was inhibited by 100% (MIC) for stevioside and steviolbioside equals 7.5 and 3.8 microg/mL, respectively. MIC values for conjugates of the hydrazides of pyridine carbonic acids and steviolbioside as well as isosteviol are in the ranges 5-10 and 10-20 microg/mL, respectively. Maximum inhibitory effect against M. tuberculosis showed the conjugates of isosteviol and adipic acid dihydrazide (MIC values ranged from 1.7 to 3.1 microg/mL). Antitubercular activity of the compounds studied is higher than the activity of antitubercular drug Pyrizanamide (MIC = 12.5-20 microg/mL) but lower than the activity of antitubercular drug Isoniazid (MIC = 0.02-0.04 microg/mL).

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.

Ent-kaurane diterpenoids and glycosides: Isolation, properties, and chemical transformations

This review is devoted to ent-kaurane diterpenoids and related glycosides, which represent two naturally occurring groups of compounds with interesting structures and properties. Much useful information about the biogenesis and biological activities of these compounds is presented; however, the greatest part of the review covers various aspects of the chemical transformations of native ent-kaurane diterpenoids, namely, their reactions via COOH, C=O, and OH groups and double bonds. Special attention is given to rearrangements of the carbon skeleton, primarily the Wagner-Meerwein rearrangement of the well-known kaurane diterpenoid steviol into its isomer, the well-known ent-beyerane diterpenoid isosteviol. A separate section is devoted to the chemical transformations of isosteviol, which are used to demonstrate how the well-known reactions of COOH and C=O groups, as well as CH2-C(O)R fragments, proceed in unusual ways when these moieties are attached to rigid hydrocarbon skeletons of naturally occurring compounds (or when they are parts of them). The final section considers ent-kaurane glycosides, focusing on those isolated from the plant Stevia rebaudiana, which is well known because they are 300–400 times sweeter than sucrose. The chemical transformations and, in some cases, biotransformations of these compounds (rebaudiosides) are described in detail, including the total synthesis of some rebaudiosides aimed at creating a production technology for low-calorie sweeteners. The review covers data published between 1964 and 2010, including original results obtained by the authors.

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 H 37 R V (minimum inhibiting concentration in the range 6.3–1.7 g/mL).

Synthesis and antimicrobial and antifungal activity of derivatives of the diterpenoid isosteviol and the glycoside steviolbioside containing onium nitrogen atoms

Previously unknown derivatives of the diterpenoid isosteviol and the glycoside steviobioside containing onium nitrogen atoms were synthesized. The antimicrobial and antifungal activities of these compounds were studied.

Reaction of isosteviol diterpenoid with selenium dioxide

Diterpenoid isosteviol was oxidized by selenium dioxide in acetic anhydride or in a mixture of acetic anhydride with dioxane to 15-oxo-derivative, whereas reaction with SeO2 in boiling ethanol led to a mixture of mono- and diselenides. Molecular structure of the monoselenide is established by the X-ray structural analysis.

Synthesis of conjugates based on chlorin and isosteviol building blocks

Conjugates containing ent-beyerane carbocyclic frameworks on the periphery of a porphyrin macrocycle were prepared by acylation of chlorin e 6 derivatives with hydroxyl and amino groups using ent-16-ketobeyeran19-oic acid chloride (diterpenoid isosteviol).

Isosteviol derivatives having azine and hydrazide fragments

Diterpenoid isosteviol (ent-16-oxobeyeran-19-oic acid) and its methyl ester and chloride reacted with hydrazine hydrate to give derivatives having azine and hydrazide fragments.