Vitamin fluorinated analogs

A. Ohno, M. Shimizu, S. Yamada, Fluorinated vitamin D analogs to probe the conformation of vitamin D in its receptor complex F-NMR studies and biological activity, Chem. Pharm. Bull. 50 (2002) 475-483. 

Fluorinated Vitamin D3 Analog with in vivo Anticancer Activity ... 

The preparation of fluorinated analogs of vitamin has been reviewed (112-114). Fluorination has been employed to prevent metabolic... 

Falecalcitriol is a fluorinated analog of vitamin Dj. It and three hydioxylated ntetabolites were resolved on a SO C C g colunui (A = 265 ran) using a 50/50 ->0/100 (at 12 min hold 3 min) water/acetonitrile gradient [1121]. Elution was complete in <15 min and peaks were baseline resolved. Peak identification was generated by EI/MS. 

Synthesis of vitamin D analogs blocked with fluorine atoms at the various carbons of the side chain (e.g., 24F2-la,25-(OH)2D3) results in molecules with ihtfull biological activity of vitamin D in vivo. 

Analogously, ethyl 4-fluoro-3-methylcrotonate is brominated with NBS in the presence of AIBN and then reacted with triethyl phosphite to produce good yields (72-78%) of a-fluorophosphonate, a key intermediate in the synthesis of fluorinated vitamin A esters (Scheme 3.3)7 Following a similar procedure (radical bromination and Michaelis-Arbuzov rearrangement), ( )-l-fluoro-3-(l-trityl-l,2,4-triazol-3-yl)-2-propenylphosphonate, a good inhibitor of imidazoleglycerol phosphate dehydratase, has been prepared in 25% overall yield. ... 

The influence of fluorine on the physical, chemical and biological properties of molecules is described. A discussion of the effect of fluorination on bond lengths and bond strengths is presented in the course of an analysis of the steric demand of fluorinated substituents. These steric effects as well as electronic interactions are illustrated in a discussion of fluorinated vitamin D3 and prostaglandin and thromboxane analogs. 

Additionally, fluorination was used to study the photochemical reaction which forms vitamin D. Both the 6-fluoro and 19,19-difluoro analogs,... 

Fluorine has also been introduced stereospecifically at the 3/ positions of la-OH-Da via hydrofluoric acid catalyzed cycloreversion of the 3,5-cyclo vitamin analog which was initially fonned by solvolysis of the 3 3-tosylate [scheme (28)] . ... 

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