Chemistry Fluoxymesterone

fluoxymesterone androstane steroid , 17α-alkylated derivative of testosterone (androst-4-en-17β-ol-3-one), , known 9α-fluoro-11β-hydroxy-17α-methyltestosterone or 9α-fluoro-11β-hydroxy-17α-methylandrost-4-en-17β-ol-3-one. testosterone fluorine atom @ c9α position, hydroxyl group @ c11β position, , methyl group @ c17α position.

synthesis

step one: first step in synthesis of fluoxymesterone microbiological oxidation of commercially available androstenedione (1.11) actinomyces; introduces hydroxyl group 11α-position (1.12), oxidised ketone using jones’ reagent, yielding 3,11,17-triketone, adrenosterone (1.13). pyrrolidine reacts form enamine (1.14) reaction 3α-keto group, protecting alkylation in subsequent step. regioselectivity of pyrrolidine reaction @ 3α-position occurs inherently in structure of adrenosterone, due position of sterically bulky methyl groups. in subsequent steps, alkylation of 17-keto group (1.14) using grignard reagent, addition of hydride @ 11-position (1.15) , regeneration of protected 3-keto group yields starting material (1.16) final steps of fluoxymesterone synthesis. involves more standard synthetic transformations.

scheme showing full synthesis of fluoxymesterone andrestenedione

steptwo: 11α-hydroxyl of starting material (1.16) sulfonylated p-toluenesulfonyl chloride; addition of trimethylamine (base) deprotonates 11α-carbon, yielding (e2) elimination of tosylate (pka - 5) give olefin (1.17). stereospecificity of reaction between olefin , hypobromous acid (hobr) in base, n-bromosuccinimide (nbs), determined formation of bromonium intermediate; electrophilic bromonium cation approaches ring’s less sterically hindered α-face , attacked π-electron density of alkene. hydroxide ion attacks above ring (β-face) @ 11-carbon, resulting in structure (1.18) stereospecific addition of hydroxyl , bromine across double bond. addition of sodium hydroxide results in deprotonation of 11α-hydroxyl, , subsequent structure undergoes intramolecular sn2 epoxy ring formation. epoxy ring of β-epoxide (1.19) protonated give oxironium ion intermediate. in concerted process, fluoride attacks ring’s α-face below, 1 of 2 oxygen-carbon bonds broken on opposite face; hence regenerating 11α-hydroxyl trans fluorine substituent. resulting structure (1.20) androgenic steroid, fluoxymesterone.

detection in body fluids

detection of halotestin , other such illegal anabolic steroids in sports achieved gs-ms identification of urinary excreted anabolic steroids , metabolites. in test halotestin, dry residue obtained urine sample dissolved in dimethylformamide , sulfur trioxide-pyridine complex , heated 1% potassium carbonate solution. halotestin , many of metabolites contain 2 polar hydroxyl groups, leading intermolecular hydrogen bonding increases boiling point , reduces volatility. in order attain gaseous sample gc-ms, products of hydrolysis extracted, dissolved in methanol , derivatised form volatile trimethylsilyl (tms) esters adding n-methyl-n-trimethylsilyl-trifluoroacetamide (mstfa) , trimethylsilylimidazole (tmsimi).