Synthesis of 6-fluorovitamin D3

Abstract

6-Fluorovitamin D3 has been synthesized starting with 6-fluoro-7-dehydrocholesteryl acetate, prepared from 6-fluorocholesteryl acetate. The irradiation preparation of the previtamin and the thermal conversion to the vitamin require special conditions. The effect of the fluorine substituent on the chemical synthesis and on the biological activity of the vitamin are discussed.

Synthesis and biological evaluation of 6-methyl analog of 1α,25-dihydroxyvitamin D3

“…Later, many other crystal structures of the LBD-VDR bound to different vitamin D compounds were solved and it became clear that VDR bound (at least in the crystalline state) the vitamin D ligands having their intercyclic C(5) C(6)-C(7) C (8) diene moiety in the s-trans conformation, exhibiting a torsion angle of ca. −149 • .…”

“…Although more than 3000 different structural analogs of the natural hormone have been obtained and tested to date [7], very few of them were characterized by substitution of the intercyclic C(5) C(6)-C(7) C(8) diene moiety. 6-Fluorovitamin D 3 (3) was synthesized by Dauben et al [8] and this compound has been shown to antagonize the activity of 1␣,25-(OH) 2 D 3 , especially intestinal calcium absorption, in vivo in chicken [9]. The synthesis of 6-methylvitamin D 3 (4) Mazur [10] using a 6-oxo-3,5-cyclovitamin D precursor; the same compound was also obtained by Yamada et al [11] by reductive thermal desulfonylation of the 6-methylated vitamin D 3 -sulfur dioxide adduct.…”

A new synthetic method of 1β- and 2β-hydroxyprovitamin D3, the precursor of the 1β- and 2β-hydroxyvitamin D3

“…The residue was subjected to column chromatography on silica gel (hexane:AcOEt, 2:1) to yield compound 9 (1.26 g, 91%). Bromohydrins (9) (1). To the THF solution (20 mL) of LiAlH 4 (0.76 g, 20 mmol), bromohydrins 9 (1.39 g, 2.0 mmol) in THF (25 mL) was added dropwise at 0 °C.…”

“…The residue was subjected to column chromatography on silica gel (hexane:AcOEt, 3:1) to yield compound 1 (0.69 g, 86%). 1β-Hydroxyprovitamin D 3 (1). White crystals, mp 175.2-178.7 °C (lit.…”

“…Vitamin D 3 is a very important regulator of calcium and phosphorus metabolism, 1 and it is now established that the active derivatives of parent D 3 mainly includes following three forms: 1α-OH-D 3 , 25-OH-D 3 and 1α,25-(OH) 2 -D 3 , 2 among which the 1α,25-(OH) 2 -D 3 is recognized as showing the highest activity of all. 3 The excellent biological activity of these three derivatives has led to various studies on synthesis and biological testing of other analogues, especially those hydroxylated at different positions of the A ring with various configurations.…”