Allogibberic Acid Research Articles

Aminodiols, aminotetraols and 1,2,3-triazoles based on allo-gibberic acid: stereoselective syntheses and antiproliferative activities.

A new series of aminodiols, aminotetraols and 1,2,3-triazoles based on allo-gibberic acid were synthesized in a stereoselective manner, starting from commercially available gibberellic acid. allo-Gibberic acid, prepared from gibberellic acid according to a literature method, was applied to SeO2/t-BuOOH-mediated allylic oxidation, yielding the triol, which is a key intermediate. After protecting the 1,4-diol functionality as acetonide, epoxidation was performed using either m-CPBA or t-BuOOH/VO(acac)2 to produce the epoxy alcohol. Then, the oxirane ring was opened with either primary amines to provide aminodiols or sodium azide to afford azido diols. The latter was subjected to the CuAAC reaction to obtain dihydroxy 1,2,3-triazoles. HCl-mediated acetonide deprotection of the prepared derivatives furnished aminotetraols and tetrahydroxy 1,2,3-triazoles. The antiproliferative effects of the prepared compounds were studied by the in vitro MTT method against a panel of human cancer cell lines (HeLa, SiHa, A2780, MCF-7 and MDA-MB-231) and fibroblasts, and the structure-activity relationships for the prepared compounds were explored.

Stereoselective synthesis and antiproliferative activity of allo-gibberic acid-based 1,3-aminoalcohol regioisomers.

A new library of allo-gibberic acid-based aminoalcohol regioisomers was synthesised stereoselectively starting from commercially available gibberellic acid, which yields allo-gibberic acid under mild acidic conditions. The successful formation of hydroxymethyl ketone derivative 5, by acid-mediated rearrangement of previously prepared epoxide, paved the way to obtain the desired 1,3-aminoalcohols through Schiff base formation. To obtain the desired regioisomers, the primary alcohol functionality of 5 was subjected to mesylation, then replaced with either primary amine or sodium azide. The formed azide derivative was subjected to either CuAAC reaction to obtain 1,2,3-triazoles or underwent Pd-catalysed hydrogenolysis to obtain primary aminoalcohol, which was further transformed into 1,3-aminoalcohols by reductive alkylation. All prepared aminoalcohols were identified in a satisfactory manner using modern spectroscopic techniques and assessed for their antiproliferative activity against a panel of human cancer cell lines. The antiproliferative effects of the prepared compounds were assayed by in vitro MTT method against a panel of human cancer cell lines (HeLa, SiHa, A2780, MCF-7 and MDA-MB-231). A significant difference was observed in the antiproliferative activity between the regioisomers. Some compounds exerted outstanding activities against the malignant cells with limited action on fibroblasts, indicating considerable cancer selectivity.

Stereoselective Synthesis and Application of Gibberellic Acid-Derived Aminodiols.

A series of gibberellic acid-based aminodiols was designed and synthesized from commercially available gibberellic acid. Exposure of gibberellic acid to hydrochloric acid under reflux conditions resulted in aromatization followed by rearrangement to form allo-gibberic acid. The key intermediate, ethyl allo-gibberate, was prepared according to literature methods. Epoxidation of key intermediate and subsequent ring-opening of the corresponding epoxide with different nucleophiles resulted in N-substituted aminodiols. The regioselective ring closure of N-benzyl-substituted aminodiol with formaldehyde was also investigated. All aminodiol derivatives were well characterized using modern spectroscopic techniques and evaluated for their antiproliferative activity against a panel of human cancer cell lines. In addition, structure–activity relationships were examined by assessing substituent effects on the aminodiol systems. The results indicated that aminodiols containing aromatic rings on their nitrogen substituents displayed significant cytotoxic effects. Among these agents, N-naphthylmethyl-substituted aminodiols were found to be the most potent candidates in this series. One of these molecules exhibited a modest cancer selectivity determined by non-cancerous fibroblast cells. A docking study was also made to exploit the observed results.

Chemical Composition and Pharmacological Activities of Plantago major L. in Vietnam

Plantago major L. in Vietnam was investigated for its chemical composition and also evaluated the biological activities against enzyme α- glucosidase and free radicals activities. The powder mixture of dried leave and roots of this species was extracted separately by three solvents: dichloromethane, water, water:alcohol (50:50, v:v). The chemical composition of dichloromethane extract was analyzed by GC-MS system to identify eighteen components, out of which eight biologically active compounds viz. 5-hydroxymethylfurfural, n-hecxadecanoic acid, 9,12-octadecadienoic acid (Z,Z)-methyl ester, allogibberic acid, β-tocopherol, campesterol, γ-sitosterol, lup-20(29)-en-3-ol and friedenlan-3-one were presented. The concentration of radical scavenging activity DPPH expressed by IC50 for water, water:alcohol (50:50, v:v) and dichloromethane with 208.7, 89.3 and 62.05 μg/mL, respectively. The dichloromethane, water and water:alcohol (50:50, v:v) extract of Plantago major exhibited α-glucosidase inhibitory activity with IC50 values of 116.4, 302.7, 195.9 μg/mL, respectively, which was comparable with acarbose (98.4 μg/mL). Plantago major L. in Vietnam may be effective inhibitors as the antidiabetic candidate and helpful to reduce the postprandial glucose levels.

Synthesis and anti-proliferative activity of allogibberic acid derivatives containing 1,2,3-triazole pharmacophore

Sixty novel allogibberic acid derivatives containing 1,2,3-triazole pharmacophore were designed and synthesized. The key chemical processes include aromatization of the A ring in gibberellins, formation of allogibberic azides and its copper mediated Huisgen 1,3-dipolar cycloaddition with alkynes. A number of hybrids containing α,β-unsaturated ketone moiety exhibited excellent in vitro cytotoxic activities. Some of the hybrids were more selective to MCF-7 and SW480 cell lines with IC50 values at least 8-fold more cytotoxic than cisplatin (DDP). The most potent compounds C43 and C45 are more cytotoxic than cisplatin (DDP) against all tested five tumor cell lines, with IC50 values of 0.25–1.72 µM. Mechanism of action studies indicated that allogibberic-triazole derivative C45 could induce the S phase cell cycle arrest and apoptosis in SMMC-7721 cell lines.

Synthesis and biological evaluation of pharbinilic acid and derivatives as NF-κB pathway inhibitors.

A 7-step synthesis of pharbinilic acid, a member of the gibberellin family of natural products and the first naturally occurring allogibberic acid, is reported. An efficient decarboxylative aromatization reaction enables the synthesis of pharbinilic acid and related analogs for evaluation as modulators of NF-κB activity. Remarkably, one analog displays a 2 μM IC50 in an NF-κB activity assay and inhibits an endogenous NF-κB-regulated pathway.

A new diterpene glycoside from the seeds of Pharbitis nil

Pharbitis nil (Convolvulaceae) is an annual climbing herb, and widely distributed throughout Korea, Japan, and China. In China, it has been used as folk medicine for treatment of a variety of digestive problems. The flowers and seeds of P. nil are known for their diversified compounds, particularly for the presence of resin glycosides, gibberellins, flavonoids, and anthocyanins. Its extract showed antitumor and anti-fungal activities. Recently, we reported the isolation from the CHCl3 and EtOAc soluble fraction, of ent-kaurane type diterpenes, lignans, phenolic amides, and allogibberic acid, which showed cytotoxic activities and the ability to inhibit NO production. In our continuing search for bioactive constituents from Korean medicinal plants, we investigated the BuOH fraction of P. nil. Repeated column chromatographic purification resulted in the isolation of one new diterpene glycoside (1), along with three known compounds (2-4). The structure of new one was determined on the basis of 1D and 2D NMR spectroscopic data and chemical means.

Pharbinilic Acid, an Allogibberic Acid from Morning Glory (Pharbitis nil)

Pharbinilic acid (1), the first naturally occurring allogibberic acid, was isolated from ethanol extracts of morning glory (Pharbitis nil) seeds. Its absolute configuration was determined by NOESY NMR and ECD experiments. Compound 1 showed weak cytotoxicity against A549, SK-OV-3, SK-MEL-2, and HCT-15 cells and weakly inhibited nitric oxide production in lipopolysaccharide-activated BV-2 microglia cells.

ChemInform Abstract: Synthesis and Mass Spectrometric Behaviour of Iodine Allogibberic Acid Compounds.

ChemInform Abstract: Synthesis and Mass Spectrometric Behaviour of Iodine Allogibberic Acid Compounds.

Synthesis and Mass Spectrometric Behaviour of Iodine Allogibberic Acid Compounds

Journal für Praktische ChemieVolume 332, Issue 5 p. 800-804 Article Synthese und massenspektroskopisches Verhalten iodhaltiger Allogibberinsäure-Verbindungen Synthesis and Mass Spectrometric Behaviour of Iodine Allogibberic Acid Compounds N. A. Pankruschina, N. A. Pankruschina Institut für Organische, Chemie der Sibirischen Abteilung der Akademie der Wissenschaften der UdSSR, Novosibirsk, UdSSRSearch for more papers by this authorA. G. Druganov, A. G. Druganov Institut für Organische, Chemie der Sibirischen Abteilung der Akademie der Wissenschaften der UdSSR, Novosibirsk, UdSSRSearch for more papers by this authorV. A. Raldugin, V. A. Raldugin Institut für Organische, Chemie der Sibirischen Abteilung der Akademie der Wissenschaften der UdSSR, Novosibirsk, UdSSRSearch for more papers by this authorDr. sc. D. Voigt, Corresponding Author Dr. sc. D. Voigt Institut für Biochemie der Pflanzen der Akademie der Wissenschaften, Weinberg 3, O-4050 HalleInstitut für Biochemie der Pflanzen der Akademie der Wissenschaften, Weinberg 3, O-4050 HalleSearch for more papers by this authorProf. Dr. G. Adam, Prof. Dr. G. Adam Institut für Biochemie der Pflanzen der Akademie der Wissenschaften, Weinberg 3, O-4050 HalleSearch for more papers by this author N. A. Pankruschina, N. A. Pankruschina Institut für Organische, Chemie der Sibirischen Abteilung der Akademie der Wissenschaften der UdSSR, Novosibirsk, UdSSRSearch for more papers by this authorA. G. Druganov, A. G. Druganov Institut für Organische, Chemie der Sibirischen Abteilung der Akademie der Wissenschaften der UdSSR, Novosibirsk, UdSSRSearch for more papers by this authorV. A. Raldugin, V. A. Raldugin Institut für Organische, Chemie der Sibirischen Abteilung der Akademie der Wissenschaften der UdSSR, Novosibirsk, UdSSRSearch for more papers by this authorDr. sc. D. Voigt, Corresponding Author Dr. sc. D. Voigt Institut für Biochemie der Pflanzen der Akademie der Wissenschaften, Weinberg 3, O-4050 HalleInstitut für Biochemie der Pflanzen der Akademie der Wissenschaften, Weinberg 3, O-4050 HalleSearch for more papers by this authorProf. Dr. G. Adam, Prof. Dr. G. Adam Institut für Biochemie der Pflanzen der Akademie der Wissenschaften, Weinberg 3, O-4050 HalleSearch for more papers by this author First published: 1990 https://doi.org/10.1002/prac.19903320533AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume332, Issue51990Pages 800-804 RelatedInformation

Proof of formation of an unstable conjugated triene on decomposition of gibberellin A3 in water

It has been shown by the methods of1H NMR and high-performance liquid chromatography with recording of UV spectra that in aqueous solutions of gibberellin A3, via gibberellenic acid, an unstable conjugated triene having λmax 326 nm is formed which is readily converted into allogibberic acid and is isolated as a mixture (1:2) with this acid. In the1H NMR spectrum of the triene, confirming its structure, spin-spin coupling both of the H-5 proton and of the protons of the methyl group with all the H-1, H-2, and the H-3 protons is observed. The precursor of allogibberic acid has been ascribed the structure of (−)-13-hydroxy-19,20-dinorgibberella-1,3,9,16-tetraen-7-oic acid with a conjugated 1,3,9-trienic system.

Intramolecular interaction in gibberic acid and its derivatives

Spectroscopic investigation (u.v., i.r. and NMR) of gibberic acid, epigibberic acid, allogibberic acid and epiallogibberic acid suggests a weak intramolecular interaction of the aromatic ring with the terminal methylene group in the case of epiallogibberic acid, and with the terminal carbonyl group in the case of epigibberic acid.

A mass spectrometric study of the pyrolysis of gibberellic acid

AbstractThe behaviour of gibberellic acid (GA3) under electron impact and chemical ionization conditions has been examined. The tendency of GA3 to undergo pyrolysis by the loss of the elements of water and carbon dioxide has been identified. Two methods of sample introduction can be used to minimize the occurrence of this pyrolysis. Accurate mass measurement allows the composition of the pyrolysis product to be determined and metastable techniques confirm the structure of this product to be epi‐allogibberic acid rather than its isomer allogibberic acid. This result corrects a misconception in the literature and illustrates the advantage of metastable methods compared with accurate mass measurements, for the determination of small structural differences within a molecule.

Photochemical and mass spectrometric transformation of gibberellenic acid to 9-epiallogibberic acid

Gibberellenic acid (2) reacted thermally in a modified immersion photochemical reactor, to give an intermediate triene (3). This triene then isomerized photochemically, via suprafacial [1,3]-hydrogen migration, to 9-epiallogibberic acid (5). On the other hand, comparison of the positive mass spectra of gibberellenic acid (2), allogibberic acid (4), and 9-epiallogibberic acid (5) showed that gibberellenic acid underwent electron impact fragmentation to the triene 3 cation. This cation then rearranged through suprafacial [1,3]-hydrogen migration to the 9-epiallogibberic acid (5) cation.

A review of chemically induced flowering in Lemna gibba G3 and Pistia stratiotes

The synthetic chelating agent EDDHA (ethylenediamine-di- o-hydroxyphenylacetic acid) and salicylic acid (SA) induce or enhance flowering in Lemna gibba L., strain G3, and Pistia stratiotes L. In L. gibba G3 these compounds also induce gibbosity, a swelling of the lower side of the fronds. EDTA (ethylenediaminetetraacetic acid) brings about similar effects in L. gibba G3. However, it is markedly less effective than EDDHA and SA and there are strong arguments in favour of a recent conclusion that it brings about its effect via a different mechanism. Ethylene induces gibbosity in L. gibba G3, however, neither in this species nor in P. stratiotes does it affect flowering. The effect of EDDHA/SA as well as ethylene on L. gibba G3 is specifically negated by autoclaved GA 3 is i.e., break-down products of GA 3 such as allogibberic acid, whereas non-autoclaved GA 3 is ineffective. On the other hand GA 3 induces profuse flowering in P. stratiotes whereas autoclaved GA 3 is less effective. In the light of the various results it could be hypothesized that a gibberellin and ethylene in combination with another factor are involved in flowering of L. gibba G3.

Photochemical synthesis of allogibberic acid

Photochemical synthesis of allogibberic acid

Mass spectroscopy of natural products. II—allogibberic acid—A model for the skeletal fragmentation of the molecular ions of GA3 type gibberellins

AbstractThe positive ion mass spectrum of allogibberic acid was examined and fragmentation routes involving the carbon skeleton are proposed on the basis of mass measurements and metastable ion observations. The results are compared with the mass spectra of 3‐hydroxy‐epiallogibberic acid, as well as gibberellin A3 (GA3), 3‐epi‐GA3, 3‐dehydro‐GA3 and iso‐GA3, the latter compounds all being capable of undergoing aromatization of ring A giving a key ion corresponding to the molecular ions of the allogibberic acid and 3‐hydroxy‐epiallogibberic acid models, respectively. All the gibberellin derivatives investigated show the same fragmentation of the skeleton. Thus, the behaviour under electron impact of the GA3 type gibberellins follows a general pattern.

Activity of the aldehyde and alcohol of gibberellins A12 and A14, two derivatives of gibberellin A15 and four decomposition products of gibberellin A3 in 13 plant bioassays

The biological activities of the aldehyde and alcohol of gibberellins (GAs) A12 and A14, 3α-OH-GA15, 3β-OH-GA15 wrong lactone (i.e. GA37 wrong lactone) and the four major decomposition products of GA3 (isogibberellic, allogibberic, epiallogibberic and Δ9(11)-dehydroallogibberic acids) were tested over a wide range of concentrations on 13 plant bioassays in order to ascertain certain of the structural requirements for biological activity. Generally modification of the basic GA-molecule decreased its activity in all assays except for derivatives of GA12 and GA14 (suggesting conversion of these derivatives to more polar, active GAs). Modification of the 3-OH from the usual 3β to 3α configuration markedly reduced activity. Neither the presence of an inverted lactone ring (i.e. 3β-OH-GA15 wrong lactone) nor changes to the lactone ring of GA3 (4→10) to form iso-GA3 (4→2) appreciably reduce activity. Further decomposition of GA3 to allogibberic and Δ9(11)-dehydroallogibberic acid reduced activity only slightly, but epimerization of allogibberic acid at C-9 essentially eliminated biological activity.

Inhibition of flowering by hexahydrofluorene-9-carboxylic acids related to allogibberic acid

1,2,3,4,4a,9a-hexahydrofluorene-9-carboxylic acid isomers have been prepared by reduction of fluorene-9-carboxylic acid. Hexahydrofluorene-9-carboxylic acid ( 5) produce inhibition of flowering and vegetative frond development in Lemna perpusilla 6746 similar to that observed with allogibberic acid. The stereochemical requirements for this type of biological activity in allogibberic acids and hexahydrofluorene-9-carboxylic acids are considered.

New intermediates in the aqueous decomposition of gibberellic acid

The decomposition pathway of gibberellic acid (I) through gibberellenic acid (III) in aqueous solution has been investigated. Decomposition of gibberellenic acid in deuterium oxide gives [9-2H]allogibberic acid (V), [9-2H]-9-epi-allogibberic acid (VI), and unlabelled 9,11-didehydroallogibberic acid (IX). Two partially characterised hydroperoxides (XV) and (XVII) have been detected as intermediates in the oxidative transformation of gibberellic acid through gibberellenic acid to 9,11-didehydroallogibberic acid. Mechanisms are proposed on the basis of these results.