- 24-Epibrassinolide at subnanomolar concentrations modulates growth and production characteristics of a mouse hybridoma
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Brassinosteroids are known to stimulate plant growth and to possess antistress activities in plants. This work was aimed at exploring possible beneficial effects of 24-epibrassinolide on cultured mammalian cells. A mouse hybridoma was cultured either in standard serum-free medium, or in medium diluted to 30%, in which the cells underwent nutritional stress. Steady-state parameters of semicontinuous cultures conducted at 24-epibrassinolide concentrations from 10-16 to 10-9 mol l-1 were evaluated. Typical effects of the agent found both in standard and in diluted media were (i) increase in the value of mitochondrial membrane potential, (ii), drop of intracellular antibody level, (iii) increase in the fraction of the cells in the G0/G1 phase, and (iv) decrease in the fraction of the cells in the S phase. Alleviation of nutritional stress manifested itself in cultures conducted in diluted media. Viable cell density was significantly higher (relative to control) at 24-epibrassinolide concentrations 10-13 and 10-12 mol l-1. The results of this exploratory study show that the plant hormone 24-epibrassinolide may induce perturbations in the cell division mechanism, in mitochondria performance, and in secreted protein synthesis in a mammalian cell line. At the lowest brassinosteroid concentrations, the number of steroid molecules in the culture was of the same order of magnitude as the number of viable cells in the culture. This implies involvement of a complex cascade mechanism, through which the steroid molecule induces alterations in gene expression leading finally to significant changes in cell culture parameters.
- Franek, Frantisek,Eckschlager, Tomas,Kohout, Ladislav
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- NEW METHOD OF PREPARATION OF BRASSINOSTEROIDS
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Brassinosteroids with lactone B-ring (II and IV) were prepared by oxidation of the corresponding 6-keto derivatives I and III without protection of the hydroxyl groups against the action of the oxidation reagent.
- Kohout, Ladislav
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- Method for synthesizing 24-epibrassinolide
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The invention belongs to the technical field of organic synthesis. Based on a seven-step synthesis process, p-toluene sulfonyl chloride is used as an acylation reagent; a manganese dioxide/air catalytic system is used in a water and methanol system; and a calcium/HMPA/R1(CH2)nR2 reduction system is used. According to the synthesis method of the 24-epibrassinolide, ergosterol is used as a startingraw material, a seven-step synthesis process is adopted, the method comprises esterification, hydrolysis, oxidation, reduction, rearrangement, dihydroxylation and lactonization; methylbenzene is usedas a solvent in the esterification process, and ergosterol reacts with benzene sulfonyl chloride in the presence of an acid-binding agent; wherein a manganese dioxide/air system is adopted in the oxidation process, methanol is used as a solvent, and oxidation is performed in air; and a calcium/R1(CH2)nR2//HMPA/reduction system is adopted in the reduction process. According to the synthesis method,the total yield is increased by 20 points or above, the product quantitative content is 85% or above, the reaction condition is mild, the technological process is short, the operation is convenient,manganese dioxide can be recycled, low toxicity and low environmental pollution are achieved, and the synthesis method is suitable for industrial production of 24-epibrassinolide.
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- Biological Activity of Brassinosteroids – Direct Comparison of Known and New Analogs in planta
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A systematic investigation of structural modifications of brassinosteroids is presented. We describe in detail their synthetic preparation, which includes significant improvements of previously reported protocols as well as access to new analogs with functional modifications of the steroid skeleton and of the C(17)-attached side chain. We report the biological potency of the prepared brassinosteroid analogs as plant hormones, which were carefully established in the French bean second internode elongation assay and discuss our observations in light of the recently reported structural data detailing the molecular interactions between brassinolide in the trimeric complex with the protein receptors kinases BRASSINOSTEROID INSENSITIVE 1 (BRI1) and SOMATIC EMBRYOGENESIS RECEPTOR KINASE 1 (SERK1). In a further part of this work we describe the preparation of H2O-soluble pro-forms of 24-epicastasterone and we discuss their physical properties, hydrolytic stabilities and biological activity.
- Wendeborn, Sebastian,Lachia, Mathilde,Jung, Pierre M. J.,Leipner, J?rg,Brocklehurst, David,De Mesmaeker, Alain,Gaus, Katharina,Mondière, Régis
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- For the preparation of 24-table brassin reduction composition of the lactone
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The invention discloses a reductive composition for preparing 24-epibrassinolide, which is applicable to an oxidizing step in preparation of the 24-epibrassinolides. The reductive composition comprises metal lithium and one or more of R1(CH2)nR2 compounds, wherein n is equal to 2-6; R1 is OH or NH2; and R2 is NH2 or OH.
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Paragraph 0053; 0073
(2017/02/24)
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- The development and use of a general route to brassinolide, its biosynthetic precursors, metabolites and analogues
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A new method for the construction of steroid side chains through the addition of lithium salts of dithianes to a C-22 aldehyde was developed. An efficient one-pot procedure for the preparation of a suitable C-22 aldehyde from commercial epibrassinolide in three steps in 86% isolated yield was described. Enantioselective hydroxymethylation of isovaleraldehyde and Kulinkovich cyclopropanation of silylated Roche esters were used as key steps for the dithiane syntheses. The method was applied for the preparation of brassinolide, its biosynthetic precursors and metabolites. In addition, a number of brassinosteroids with a double bond in the side chain were prepared as precursors for tritiated derivatives for biosynthetic studies.
- Hurski,Ermolovich,Zhabinskii,Khripach
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p. 1446 - 1452
(2015/01/30)
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- Synthesis of fatty acyl derivatives of 24-epibrassinolide
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A number of fatty acid (palmitic, myristic and lauric) esters (both 3α- and 3β-isomers) of epibrassinolide has been prepared as reference compounds for metabolic studies. Selective protection of the three of four hydroxyl groups of epibrassinolide was successively performed first as cyclic 22,23-methylboronates and then as 2α-benzyl ethers. α,β- Inversion of C-3 hydroxyl group was achieved through a consecutive oxidation-reduction reactions or by a nucleophilic substitution of the 3α-mesylates. Treatment of the 3α- and 3β-alcohols with palmitic, myristinic or lauric acid chlorides gave the corresponding esters. The hydrolysis of 22,23-methylboronates was performed after their transformation into 2-hydroxy-1,3,2-dioxaborolanes using a cation exchange column with DOWEX 50WX8 in NH4+ form. Hydrogenolysis of the benzyl ethers catalyzed by palladium yielded the target compounds. This article is part of a Special Issue entitled Synthesis and biological testing of steroid derivatives as inhibitors .
- Khripach, Vladimir A.,Zhabinskii, Vladimir N.,Tsavlovskii, Dmitrii V.
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p. 345 - 354
(2013/11/19)
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- A general approach to synthesis of labeled brassinosteroids: Preparation of [25,26,27-2h7]brassinolide with 60% isotopic purity from the parent brassinolide
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From brassinolide (BL) 1, [25,26,27-2H(n)]BL 10 was synthesized in 5 steps including C-25 hydroxylation, dehydration and catalytic deuteriogenation. In direct oxy-functionalization of tetra-O-acetyl BL 2 with methyl(trifluoromethyl)dioxirane leading to 25-hydroxyl compound 3, 14- hydroxyl, 25-hydroxy-15-oxo and 14,25-dihydroxyl derivatives, 4, 5 and 6, were newly identified; the catalytic deuteriogenation of Δ(25(26))-BL 8 using 5% palladium-on-charcoal resulted in abundant incorporation of deuterium atoms to give 10 with 60% isotopic purity of [25,26,27-2H7]BL.
- Seto, Hideharu,Fujioka, Shozo,Koshino, Hiroyuki,Yoshida, Shigeo,Watanabe, Tsuyoshi,Takatsuto, Suguru
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p. 7525 - 7528
(2007/10/03)
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- IMPROVED SYNTHESIS OF EPIBRASSINOLIDE
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An improved synthesis of epibrassinolide is described.The product is the first of a group of brassinosteroids, which has found use a plant growth regulator.Among the proposed improvements for its production the most important position is the development of a stereoselective method for construction of the side chain by the oxidation of the Δ22-bond with osmium tetroxide in the presence of 10,11-dihydroquinidine p-chlorobenzoate.
- Khripach, V. A.,Zhabinskii, V. A.,Ol'khovik, V. K.,Ivanova, G. I.,Zhernosek, E. V.,Kotyatkina, A. I.
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p. 1735 - 1740
(2007/10/03)
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- STEREOCONTROLLED SYNTHESIS OF THE BRASSINOLIDE SIDE CHAIN VIA A PYRANONE DERIVATIVE
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A new method for assembling the brassinolide side chain from 20-carboxaldehyde 2 was developed via the stereoselective construction of the pyranone moiety as key steps.
- Kametani, Tetsuji,Keino, Katsuyuki,Kigawa. Masaharu,Tsubuki, Masayoshi,Honda, Toshio
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p. 3141 - 3142
(2007/10/02)
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- Studies on Steroidal Plant-Growth Regulators: A New Synthesis of Brassinosteroids
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Two brassinosteroids (stereoisomers of brassinolide), (22R,23R,24R)-2α,3α,22,23-tetrahydroxy-B-homo-7-oxa-5α-ergostan-6-one (2) and (22S,23S,24R)-2α,3α,22,23-tetrahydroxy-B-homo-7-oxa-5α-ergostan-6-one (3), were synthesized from ergosterol in eight steps in ca. 30percent overall yield.The key step is the highly regioselective formation of the 7-oxalactone ring by oxidation of an enol silyl ether with 3-chloroperoxybenzoic acid.
- Zhou, Wei-Shan,Zhou, Yi-Pine,Jiang, Biao
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p. 426 - 427
(2007/10/02)
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- Short-Step Synthesis of Plant Growth-Promoting Brassinosteroids
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Brassinolide analogues, (22R,23R,24R)-2α,3α,22,23-tetrahydroxy-B-homo-7-oxa-5α-ergostan-6-one (24-epibrassinolide) (10) and (22S,23S,24R)-2α,3α,22,23-terahydroxy-B-homo-7-oxa-5α-ergostan-6-one (9), were synthesized from brassicasterol (3a) in five steps and with ca. 20percent overall yield.The key steps are the direct formation of (22E,24R)-3α,5-cyclo-5α-ergost-22-en-6-one (4) from brassicasterol mesylate (3b), the acid-catalyzed rearrangement of 4 to (22E,24R)-5α-ergosta-2,22-dien-6-one (6), and the Baeyer-Villiger oxidation of the tetrahydroxy-5α-ergostan-6-ones 7 and 8.Keywords - brassinolide; brassinosteroid; plant growth hormone; brassicasterol; Baeyer-Villiger oxidation
- Takatsuto, Suguru,Ikekawa, Nobuo
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p. 2001 - 2004
(2007/10/02)
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- A New Synthesis of Brassino Steroids: Plant Growth Promoting Steroids
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(22R,23R)- and (22S,23S)-2α,3α,22,23-Tetrahydroxy-B-homo-7-oxa-5α-ergostan-6-one, two physiologically active brassino steroids, have been synthesized via key intermediate brassicasterol obtained in a very simple way by reduction with lithium dissolved in ethylamine of the 1,4-cycloadduct of ergosterol and 4-phenyl-1,2,4-triazoline-3,5-dione.
- Anastasia, Mario,Ciuffreda, Pierangela,Fiecchi, Alberto
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p. 379 - 382
(2007/10/02)
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- Synthesis and biological activity of brassinolide and its 22 beta, 23 beta-isomer: novel plant growth-promoting steroids.
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Brassinolide (2 alpha, 3 alpha, 22 alpha, 23 alpha-tetrahydroxy-24 alpha-methyl -B-homo-7-oxa-5 alpha-cholestan-6-one), a novel plant growth-promoting steroid isolated from rape pollen, and its hitherto unknown 22 beta, 23 beta-isomer were synthesized from a C-24 epimeric 60:40 mixture of 22-dehydroxampesterol (24 alpha-methyl) and brassicasterol (24 beta-methyl) from oysters. The method of synthesis favored the formation of the 22 beta, 23 beta-isomer by better than 4:1. Comparative plant growth-promoting capabilities of brassinolide, both natural and synthetic, and its three side chain cis-glycolic isomers in the bean second internode bioassay showed that the natural and synthetic brassinolides were equally active and caused splitting of the internode at the 0.1 microgram level. The least active was the 22 beta, 23 beta-isomer of brassinolide. The isomers with the 22 alpha, 23 alpha and 24 alpha, and the 22 beta, 23 beta and 24 beta configurations were highly active and were required at about 10 times the concentration of brassinolide to cause the same physiological response. In the bean first internode bioassay, an auxin-induced growth test system which employs isolated bean plant segments, the isomer with 22 beta, 23 beta and 24 beta configuration caused a greater response than brassinolide. Two of the four tetrahydroxy ketones obtained in the synthesis of the isomers were also active in both assays.
- Thompson,Mandava,Meudt,Lusby,Spaulding
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p. 567 - 580
(2007/10/02)
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