26538-44-3

Usage

Uses

Used in Livestock Industry:
Zeranol is used as an animal growth promotant for enhancing the growth and development of livestock. It acts as an anabolic agent, stimulating muscle growth and improving feed efficiency in animals.
Used in Pharmaceutical Industry:
Although not explicitly mentioned in the provided materials, due to its estrogenic activity, zeranol may also have potential applications in the pharmaceutical industry for the development of drugs targeting hormone-related conditions. However,

Originator

Ralone,I.C.I. ,Italy ,1975

Manufacturing Process

A spore sand culture containing Gibberella zeae (Gordon) NRR L-2830 was aseptically placed in a sterile tube containing 15 ml of Czapek's-Dox solution and a small amount of agar. This medium was then incubated for about 168 hours at approximately 25°C. At the end of the incubation period, the medium was washed with 5 ml of sterile deionized water and transferred to a sterile tube containing 45 ml of Czapek's-Dox solution. The contents of the tube were then incubated for about 96 hours at about 25°C after which the material was available for use in inoculation of a fermentation medium. To a 2-liter flask were added 300 g of finely divided corn. The flask and its contents were then sterilized and after sterilization 150 ml of sterile deionized water were added. To the mixture in the flask were then added 45 ml of the inoculum prepared by the process and the material was thoroughly mixed. The mixed material was then incubated for about 20 days at 25°C in a dark room in a water-saturated atmosphere. The following illustrates the recovery of the anabolic substance from the fermentation medium. A 300 g portion of fermented material was placed in 500 ml of deionized water and slurried. The slurry was then heated for about 15 minutes at 75°C, 300 g of filter aid were then added and the material was filtered. The solid filtered material containing the anabolic substance was then air dried, and 333 g of the dried cake were then extracted with 500 ml of ethanol. This procedure was repeated three more times. The ethanol extract was then dried under vacuum to give 6.84 g of solid material. This solid material was then dissolved in 20 ml of chloroform and extracted with 30 ml of an aqueous solution containing 5% by weight of sodium carbonate having an adjusted pH of about 11.2. The extraction process was repeated seven more times. The pH of the sodium carbonate extract was then adjusted to 6.2 with hydrochloric acid, to yield an anabolic substance containing precipitate. The precipitate and the aqueous sodium carbonate extract were then each in turn extracted with 75 ml of ethyl ether. This procedure was repeated three more times to yield a light yellow ethereal solution, which was then dried to yield 116 mg of solid anabolic substance. This material was then subjected to multiple transfer countercurrent distribution using 100 tubes and a solvent system consisting of two parts chloroform and two parts methanol and one part water as the upper phase, all parts by volume. The solid material obtained from the multiple transfer counter-current distribution was then tested for physiological activity according to the well-known mouse-uterine test. The fermentation estrogenic substance produced has the formula: Tetrahydro F.E.S. was produced by dissolving 0.5 g F.E.S. in 200 ml of ethanol. The F.E.S. was reduced by contacting the solution with hydrogen for 3 hours at 30°C and 1,000 psi using 2 g of Raney nickel as a catalyst. After filtering and concentrating the reaction mixture, the product was washed with 2 to 3 ml of 2-nitropropane and crystallized. It was found to have a melting point from 143°C to 160°C.

Therapeutic Function

Estrogen

Air & Water Reactions

Insoluble in water.

Reactivity Profile

Zeranol is an alcohol. Flammable and/or toxic gases are generated by the combination of alcohols with alkali metals, nitrides, and strong reducing agents. They react with oxoacids and carboxylic acids to form esters plus water. Oxidizing agents convert them to aldehydes or ketones. Alcohols exhibit both weak acid and weak base behavior. They may initiate the polymerization of isocyanates and epoxides.

Health Hazard

ACUTE/CHRONIC HAZARDS: When heated to decomposition Zeranol emits acrid smoke and irritating fumes.

Fire Hazard

Flash point data for Zeranol are not available; however, Zeranol is probably combustible.

Safety Profile

An experimental teratogen. Experimental reproductive effects. Mutation data reported. When heated to decomposition it emits acrid smoke and irritating fumes.

InChI:InChI=1/C18H26O5/c1-12-6-5-9-14(19)8-4-2-3-7-13-10-15(20)11-16(21)17(13)18(22)23-12/h10-12,14,19-21H,2-9H2,1H3/t12-,14+/m0/s1

Synthetic route

(3S,7R)-14,16-di-O-benzyl-3,4,5,6,7,8,9,10-octahydro-7,14,16-trihydroxy-3-methyl-1H-2-benzoxacyclotetradecin-1-one (106315-76-8) → zeranol (26538-44-3)

Conditions	Yield
With hydrogen; Ra-Ni catalyst In ethanol under 3040 Torr; for 6h;	86%

α-zearalenol (36455-72-8) → zeranol (26538-44-3)

Conditions	Yield
With 5 mol% Pd/C; hydrogen In ethanol at 20℃;	79%
With hydrogen; palladium on activated charcoal at 20℃; under 750.075 Torr;

zearalenone (17924-92-4) → zeranol (26538-44-3)

Conditions	Yield
Stage #1: zearalenone With isopropyl alcohol; aluminum isopropoxide at 75℃; for 24h; Meerwein-Ponndorf-Verley Reduction; Stage #2: With hydrogen; palladium 10% on activated carbon In methanol at 20℃; under 760.051 Torr;	45%
With dipotassium hydrogenphosphate; sodium chloride In N,N-dimethyl-formamide glucose, yeast extract, neopeptone, Aspergillus ochraceous NRRL 405;	20%
Multi-step reaction with 2 steps 1: sodium tetrahydroborate / methanol / 3 h / 0 - 20 °C / Inert atmosphere 2: hydrogen; 5 mol% Pd/C / ethanol / 20 °C View Scheme

(3S,7R)-7,14,16-trihydroxy-3-methyl-3,4,5,6,7,8,9,10,11,12-decahydro-1H-2-benzoxacyclotetradecin-1-one (325142-22-1) → taleranol (42422-68-4) + zeranol (26538-44-3)

Conditions	Yield
With water at 40℃; for 96h; lipases from pseudomonas species; other lipases; Yield given. Yields of byproduct given;
With water at 40℃; for 96h; lipases from pseudomonas species, other lipases; Yield given. Yields of byproduct given;

Acetic acid (S)-2,4-dihydroxy-7-methyl-5-oxo-7,8,9,10,11,12,13,14,15,16-decahydro-5H-6-oxa-benzocyclotetradecen-11-yl ester (37786-44-0, 39594-22-4, 39594-23-5) → taleranol (42422-68-4) + zeranol (26538-44-3)

Conditions	Yield
With water at 40℃; for 96h; lipases from pseudomonas fluorescens; other lipases; Yield given. Yields of byproduct given;
With water at 40℃; for 96h; lipases from pseudomonas fluorescens, other lipases; Yield given. Yields of byproduct given;

Upstream product

• 17924-92-4 zearalenone 
• 34297-69-3 2-<10(S)-Hydroxy-6-oxo-trans-1-undecenyl>-4,6-bis(benzyloxy)benzoic Acid μ-Lacton 
• 36455-72-8 α-zearalenol 
• 106315-76-8 (3S,7R)-14,16-di-O-benzyl-3,4,5,6,7,8,9,10-octahydro-7,14,16-trihydroxy-3-methyl-1H-2-benzoxacyclotetradecin-1-one 
• 37786-44-0 Acetic acid (S)-2,4-dihydroxy-7-methyl-5-oxo-7,8,9,10,11,12,13,14,15,16-decahydro-5H-6-oxa-benzocyclotetradecen-11-yl ester 
• 325142-22-1 (3S,7R)-7,14,16-trihydroxy-3-methyl-3,4,5,6,7,8,9,10,11,12-decahydro-1H-2-benzoxacyclotetradecin-1-one 

Downstream Products

• 103-29-7 1,1'-(1,2-ethanediyl)bisbenzene 
• 42422-68-4 taleranol 

Relevant academic research and scientific papers

Enzymatic kinetic separation of stereoisomeric macrocyclic lactone derivatives, 7α,β-O-acyl trans-zearalenols and 7α,β-O-acyl zearanols

Diastereomeric mixtures of resorcyclic acid macrocyclic lactones, 7α,β-O-acyl zearalenols (1,2 and 3,4 full name: trans-3,4,5,6,9,10-octahydro-14,16-dihydroxy-7-acyloxy-3-methyl 1H-2-benzoxacyclotetradecin-1-ones (3S,7S or 3S,7R)), and 7α,β-acyl zearanols

Pochonins A-F, new antiviral and antiparasitic resorcylic acid lactones from Pochonia chlamydosporia var. catenulata

Monorden (1) and the novel resorcylic acid lactones pochonins A (2), B (4), C (6), D (7), and E (8) as well as tetrahydromonorden (5) and pseurotin A (22) were isolated from cultures of the clavicipitaceous hyphomycete Pochonia chlamydosporia var. catenulata strain P 0297. Fermentation of P 0297 in bromide-containing culture media led to a shift in secondary metabolite production and yielded monocillins III (3) and II (9) as major metabolites besides monorden (1) as well as the novel compounds pochonin F (10) and a monocillin II glycoside (11) as minor metabolites. Most of these compounds showed moderate activities in a cellular replication assay against Herpes Simplex Virus 1 (HSV1) and against the parasitic protozoan Eimeria tenella. In contrast to the structurally related zearalenone derivatives none of the metabolites of strain P 0297 were found to be active in a fluorescence polarization assay for determination of modulatory activities on the human estrogenic receptor ERβ. β-Zearalenol (17), but not zearalenone (15) and α-zearalenol (16), showed antiherpetic effects. We report the production, isolation, and structure elucidation of compounds 1-11 and their biological characterization.

Synthesis and cytotoxic activities of semisynthetic zearalenone analogues

Zearalenone is a β-resorcylic acid macrolide with various biological activities. Herein we report the synthesis and cytotoxic activities of 34 zearalenone analogues against human oral epidermoid carcinoma (KB) and human breast adenocarcinoma (MCF-7) cells as well as noncancerous Vero cells. Some zearalenone analogues showed moderately enhanced cytotoxic activities against the two cancer cell lines. We have discovered the potential lead compounds with diminished or no cytotoxicity to Vero cells. Preliminary structure–activity relationship studies revealed that the double bond at the 1′ and 2′ positions of zearalenone core was crucial for cytotoxic activities on both cell lines. In addition, for zearalenol analogues, the unprotected hydroxyl group at C-2 and an alkoxy substituent at C-4 played key roles on cytotoxic effects of both cell lines.

A PROCESS FOR MANUFACTURING ZERANOL

This invention is directed generally to a process for producing Zeranol that eliminates high pressure and high temperature hydrogenations and provides high selectivity for Zeranol at improved yields.

FLUORESCENCE BASED DETECTION OF SUBSTANCES

A method for the fluorescent detection of a substance, the method comprising providing particles comprising a metal or a metal oxide core, wherein one or more optionally fluorescently tagged antibodies or human specific peptide nucleic acid (PNA) oligomers for binding to a substance is/are bound, directly or indirectly, to the surface of the metal or metal oxide; contacting a substrate, which may or may not have the substance on its surface, with the particles for a time sufficient to allow the antibody/PNA oligomer to bind with the substance; removing those particles which have not bound to the substrate; if the antibodies or PNA oligomers are not fluorescently tagged, contacting the substrate with one or more fluorophores that selectively bind with the antibody and/or substance, then optionally washing the substrate to remove unbound fluorophores; and illuminating the substrate with appropriate radiation to show the fluorophores on the substrate.

Microbial Transformation of Zearalenone. 2. Reduction, Hydroxylation, and Methylation Products

Microbial transformations have been employed as a means of preparing analogues of the resorcylic acid lactone zearalenone.Microbial transformation products were initially identified by thin-layer chromatography of fermentation extracts and then prepared by large-scale incubations.Each metabolite was subjected to structural elucidation employing carbon-13 and proton NMR, mass spectrometry, and infrared analysis.Metabolites were identified as α- and β-zearalenol, α- and β-zearalanol, zearalanone, 8'(S)-hydroxyzearalenone, 2,4-dimethoxyzearalenone, and 2-methoxyzearalenone.Binding affinities to rat uterine estrogen receptors were carried out.Only those metabolites having a free 4-phenolic group were capable of binding to the estrogen receptor.However, 8'-hydroxyzearalenone, even with a 4-phenolic hydroxyl, did not bind to the receptor.It is possible that hydrogen bonding of the aliphatic hydroxyl groups to the C-6' carbonyl of zearalenone or equilibrium between the hydroxy ketone and its tautomeric hemiketal may lead to distortion of the conformation of the molecule resulting in loss of binding to the receptor.