4-Fluoroprogesterone

T. Irie, K. Fukushi, T. Ido, T. Nozaki, Y. Kasida, F-18-labeled fluorination by crown ether metal fluoride. 1. On labeling F-18-21-fluoroprogesterone, Int. J. Appl. Radiat. Isot. 33 (1982) 1449-1452. 

HGl bubbled vigorously during 3-4 min. to saturation into a well-stirred soln. of 17-acetoxy-21-fluoroprogesterone and 2,3-dichloro-5,6-dicyanobenzoquinone... 

Bromo [ F]fluoride (Section 3.9.1) addition across a double bond was used in the synthesis of fluorine-18-labelled steroids of high specific radioactivity. After addition, the bromine is removed by reduction or by dehydrobromination. [ F]Fluoro-5a-dihydrotestosterone was obtained in about 3% radiochemical yield (Scheme 17) [64] and 6a-p F]fluoroprogesterone in only 0.3% [65]. The yields were quite low but sufficient to allow for animal studies. These reactions had been tested out successfully with simpler model alkenes [66]. 

Y.S. Choe, T.A. Bonasera, D.Y. Chi, M.J. Welch, J.A. Katzenellenbogen, 6-alpha-[F-18]fluoroprogesterone—Synthesis via halofluorination-oxidation, receptor-binding and tissue distribution, Nucl. Med. Biol. 22 (1995) 635-642. 

Addition to unsaturated steroids. The reagent adds slowly to testosterone acetate (a deactivated olefln) to give 4-fluorotestosterone. Pregnenolone acetate (1) affords an adduct (2) in modest yield, characterized by conversion into 6a-fluoroprogesterone, but the major product is a mixture of fluorinated by-products. 

This marked difference in reactivity is also observed when progesterone is reacted with pyrrolidine. This reaction proceeds to yield the enamine 7-1 from reaction at C3 (Scheme 6.7). Reaction of that enamine with perchloryl fluoride (FCIO3) followed by hydrolysis of the enamine gives the 4-fluoro derivative 7-2 of undefined stereochemistry. Treatment with acid shifts the olefin into conjugation to afford 4-fluoroprogesterone (7-3). 

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