427-79-2

Usage

InChI:InChI=1/C18H20O3/c1-10-4-3-5-12-13-6-7-18(21)9-17(13,8-11(18)2)15(14(10)12)16(19)20/h3-5,13,15,21H,2,6-9H2,1H3,(H,19,20)/t13-,15-,17+,18+/m1/s1

Upstream product

• 546-09-8 gibberellenic acid 
• 7647-01-0 hydrogenchloride 
• 7732-18-5 water 
• 77-06-5 (3S,3aS,4S,4aS,6S,8aR,8bR,11S)-6,11-dihydroxy-3-methyl-12-methylene-2-oxo-4a,6-ethano-3,8b-prop-1-enoperhydroindeno[1,2-b]furan-4-carboxylic acid 
• 77-06-5 gibberellic acid 

Downstream Products

• 427-78-1 (4bS,7S,9aS,10R)-1,7-dimethyl-8-oxo-4b,6,7,8,9,10-hexahydro-5H-7,9a-methanobenzo[a]azulene-10-carboxylic acid 
• 1422160-48-2 4-nitrobenzyl (3S,9R,9aR)-8-methyl-2-methylene-11-oxo-1,2,3,9-tetrahydro-3,9a-ethanofluorene-9-carboxylate 
• 95677-49-9 C₂₅H₂₈O₄S 

Relevant academic research and scientific papers

Gibberellin JRA-003: A Selective Inhibitor of Nuclear Translocation of IKKα

The small molecule gibberellin JRA-003 was identified as an inhibitor of the NF-kB (nuclear kappa-light-chain-enhancer of activated B cells) pathway. Here we find that JRA-003 binds to and significantly inhibits the nuclear translocation of pathway-activating kinases IKKα (IκB kinase alpha) and IKKβ (IκB kinase beta). Analogs of JRA-003 were synthesized and NF-κB-inhibiting gibberellins were found to be cytotoxic in cancer-derived cell lines (HS 578T, HCC 1599, RC-K8, Sud-HL4, CA 46, and NCIH 4466). Not only was JRA-003 identified as the most potent synthetic gibberellin against cancer-derived cell lines, it displayed no cytotoxicity in cells derived from noncancerous sources (HEK 293T, HS 578BST, HS 888Lu, HS 895Sk, HUVEC). This selectivity suggests a promising approach for the development of new therapeutics.

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.

A ring-distortion strategy to construct stereochemically complex and structurally diverse compounds from natural products

High-throughput screening is the dominant method used to identify lead compounds in drug discovery. As such, the makeup of screening libraries largely dictates the biological targets that can be modulated and the therapeutics that can be developed. Unfortunately, most compound-screening collections consist principally of planar molecules with little structural or stereochemical complexity, compounds that do not offer the arrangement of chemical functionality necessary for the modulation of many drug targets. Here we describe a novel, general and facile strategy for the creation of diverse compounds with high structural and stereochemical complexity using readily available natural products as synthetic starting points. We show through the evaluation of chemical properties (which include fraction of sp 3 carbons, ClogP and the number of stereogenic centres) that these compounds are significantly more complex and diverse than those in standard screening collections, and we give guidelines for the application of this strategy to any suitable natural product.

PROOF OF FORMATION OF AN UNSTABLE CONJUGATED TRIENE ON DECOMPOSITION OF GIBBERELLIN A3 IN WATER

It has been shown by the methods of 1H 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 the 1H 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.

The Conversion of Gibberellic Acid into Steroid Analogues

The expansion of ring B of the gibberellins by formolysis of the toluene-p-sulphonate of the 7-hydroxymethyl analogue of gibberic acid affords the steroid analogue, 4-methyl-15(14->8α)-abeo-16-noroestra-1,3,5(10)-trien-17-one.

1β-Hydroxygibberellin A5. Preparation and Comparison with Gibberellin A3

The preparation of 1β-hydroxygibberellin A5 from gibberellin A3 is described.Unlike its naturally occurring allylic isomer gibberellin A3, 1β-hydroxygibberellin A5 is stable to aqueous alkali and acid-catalysed aromatisation of ring A does not occur.Reasons for these differences, and for the hitherto unreported 3-epimerisation of gibberellin A3 by base, are discussed in terms of O-alkyl fission of the lactone bridge.