855-55-0Relevant academic research and scientific papers
Kinetics of Electrophilic Fluorination of Steroids and Epimerisation of Fluorosteroids
Rozatian, Neshat,Harsanyi, Antal,Murray, Ben J.,Hampton, Alexander S.,Chin, Emily J.,Cook, Alexander S.,Hodgson, David R. W.,Sandford, Graham
supporting information, p. 12027 - 12035 (2020/08/28)
Fluorinated steroids, which are synthesised by electrophilic fluorination, form a significant proportion of marketed pharmaceuticals. To gain quantitative information on fluorination at the 6-position of steroids, kinetics studies were conducted on enol ester derivatives of progesterone, testosterone, cholestenone and hydrocortisone with a series of electrophilic N?F reagents. The stereoselectivities of fluorination reactions of progesterone enol acetate and the kinetic effects of additives, including methanol and water, were investigated. The kinetics of epimerisation of 6β-fluoroprogesterone to the more pharmacologically active 6α-fluoroprogesterone isomer in HCl/acetic acid solutions are detailed.
Synthesis, Properties, and Reactivity of N,N'-Difluorobipyridinium and Related Salts and Their Applications as Reactive and Easy-To-Handle Electrophilic Fluorinating Agents with High Effective Fluorine Content
Umemoto, Teruo,Nagayoshi, Masayuki,Adachi, Kenji,Tomizawa, Ginjiro
, p. 3379 - 3385 (2007/10/03)
N,N′-Difluoro-2,2′-, -2,4′-, -3,3′-, -4,4′-bipyridinium and substituted N,N′-difluoro-2,2′-bipyridinmm bis(triflates), bis(tetrafluoroborates), bis(hexafluorophosphates), and bis(hexafluoroantimonates) 1-9 were synthesized in high yields by the direct fluorination of a mixture of a bipyridyl and a Lewis acid, a Br?nsted acid, or the alkali metal salt of an acid. The higher homologues, trimer 10 and polymer 11, were also synthesized. Unsubstituted or electron-donating group-substituted N,N′- difluorobipyridinium salts are stable nonhygroscopic crystals, while the electron-withdrawing group- substituted N,N′-diflurobipyridinium salts 3, 5, and 6 are moisture-sensitive crystals. Hydrolysis of 1b in boiling water gave 3,3′-dihydroxy-2,2′-bipyridyl. The reactivity determination indicated that the fluorinating capability decreased in the order 2,2′- ? 2,4' > 3,3′- ≈ 4,4′-isomer ? N-fluoropyridinium salt and that the two N-F moieties in a molecule were effective for fluorination. This fluorination occurred in a step-by-step manner, and the reactivity difference between the first and second fluorinations was very small. N,N′-Difluoro-2,2′-bipyridinium bis(tetrafluoroborate) (1b) is thus shown to be a highly reactive and easy-to-handle electrophilic fluorinating agent with the high effective fluorine content (103.3 g/kg) for preparing many fluoro organic compounds.
Synthesis of C-6 fluoroandrogens: Evaluation of ligands for tumor receptor imaging
Choe, Yearn Seong,Katzenellenbogen, John A.
, p. 414 - 422 (2007/10/02)
Seven androgens, substituted with fluorine at C-6, were prepared as potential imaging agents for androgen receptor-positive prostate tumors and were evaluated in vitro in terms of their lipophilicity and their relative binding affinities (RBA, relative to R1881 = 100) for the androgen receptor and for sex steroid binding protein.Introduction of a fluorine atom into the C-6 position of an androgen generally decreases binding affinity to the androgen receptor, except in the two cases: 6α-fluoro-19-nor-testosterone RBA = 41.6 versus 30.6 for the unsubstituted steroid) and 6α-fluorotestosterone (RBA = 8.9 versus 6.6).Receptor binding of the C-6 fluoro-androgens is also stereospecific, showing higher binding affinities for the α-epimers compared to the corresponding β-epimers (4:1 - 15:1).Binding affinity to sex steroid binding protein is the lowest with 19-nor-testosterone, which is also the least lipophilic androgen studied.Based on the binding properties of compounds in this series, 6α-fluoro-19-nor-testosterone appears to have the most promise as a tumor imaging agent. - Keywords: C-6-fluoroandrogens; fluorine substitution; relative binding affinity; 6α- and 6β-epimers; log Po/w; prostate tumors
1-Alkyl-4-fluoro-1,4-diazoniabicyclooctane Salts: a Novel Family of Electrophilic Fluorinating Agents
Banks, R. Eric,Mohialdin-Khaffaf, Suad N.,Lai, G. Sankar,Sharif, Iqbal,Syvret, Robert G.
, p. 595 - 596 (2007/10/02)
Members of a new series of solid, easily handled, storable, transportable, commercially viable, site-selective electrophilic fluorinating agents of the +N-F class (tradenamed Selectfluor reagents) have been synthesized via direct fluorination of monoquaternary salts of 1,4-diazabicyclooctane.
Power and structure-variable fluorinating agents. The N-fluoropyridinium salt system
Umemoto, Teruo,Fukami, Shinji,Tomizawa, Ginjiro,Harasawa, Kikuko,Kawada, Kosuke,Tomita, Kyoichi
, p. 8563 - 8575 (2007/10/02)
The usefulness of the N-fluoropyridinium salt system as a source of fluorinating agents was examined by using substituted or unsubstituted N-fluoropyridinium triflates 1-11, N-fluoropyridinium salts possessing other counteranions 1a-d and 3a, and the counteranion-bound salts, N-fluoropyridinium-2-sulfonates 12 and 13. Electrophilic fluorinating power was found to vary remarkably according to the electronic nature of the ring substituents. This power increased as the electron density of positive nitrogen sites decreased, and this was correlated to the pKa values of the corresponding pyridines. By virtue of this variation, it was possible to fluorinate a wide range of nucleophilic substrates differing in reactivity. It is thus possible to fluorinate aromatics, carbanions, active methylene compounds, enol alkyl or silyl ethers, vinyl acetates, ketene silyl acetals, and olefins through the proper use of salts pentachloro 6 through 2,4,6-trimethyl 2, their power decreasing in this order. All the reactions could be explained on the basis of a one-electron-transfer mechanism. N-Fluoropyridinium salts showed high chemoselectivity in fluorination, the extent depending on the reactive moiety. In consideration of these Findings, selective 9α-fluorination of steroids was carried out by reacting 1 with tris(trimethylsilyl ether) 73 of a triketo steroid. Regio- or stereoselectivity in fluorination was determined by a N-fluoropyridinium salt structure. Steric bulkiness of the N-F surroundings hindered the ortho fluorination of phenols and aniline derivatives, while the capacity for hydrogen bonding on the part of the counteranions prompted this process, and the counteranion-bound salts 12 and 13 underwent this fluorination exclusively or almost so. Both bulky N-fluoropyridinium triflates 2 and 7 preferentially attacked the 6-position of the conjugated vinyl ester of a steroid from the unhindered β-direction to give a thermally unstable 6β-fluoro isomer. On the basis of these results, N-fluoropyridinium salts may be concluded to constitute a system that can serve as a source of the most ideal fluorinating agents for conducting desired selective fluorination through fluorinating capacity or structural alteration.
N-FLUOROPYRIDINIUM TRIFLATE AND ITS DERIVATES: USEFUL FLUORINATING AGENTS
Umemoto, Teruo,Kawada, Kosuke,Tomita, Kyoichi
, p. 4465 - 4468 (2007/10/02)
N-Fluoropyridinium triflate and its derivates, stable and nonhygroscopic crystals, were found to be widely applicable reagents for mild and selective fluorination of a variety of organic compounds.
TAMING ELEMENTAL FLUORINE: INDIRECT USE OF FLUORINE FOR THE SYNTHESIS OF α-FLUOROKETONES
Rozen Shlomo,Menahem, Ynon
, p. 19 - 32 (2007/10/02)
Fluorine and sodium trifloroacetate react at -75 deg to produce a variety of fluoroxy-compounds.Although it is possible to direct the reaction towards the formation of CF3COOF or CF3CF2O, mixtures may be used when only the electrophilic fluorine has to be
