Synthesis and metabolic studies of 1α,2α,25-, 1α,4α,25- and 1α,4β,25-trihydroxyvitamin D3

The Centennial Collection of VDR Ligands: Metabolites, Analogs, Hybrids and Non-Secosteroidal Ligands

“…Figure 24 (2014-2015) [322][323][324][325][326][327][328][329][330][331][332][333][334][335][336]. 1α,20S,24R-Trihydroxyvitamin D 3 (1410) [332] showed a higher degree of activation, anti-inflammatory activity, and antiproliferative activity than vitamin D 3 receptor.…”

4-Hydroxy-1α,25-Dihydroxyvitamin D3: Synthesis and Structure–Function Study

“…Compounds 1,4α,25D 3 (1a) and 1,4β,25D 3 (1b) were synthesized as follows: the A-ring precursors enyne 2a and 2b were synthesized from methyl α-D-glucopyranoside by our reported procedures [17], and stereochemistry at the C4-position (4R) of major product 2b was determined by the modified Mosher's method (Scheme 1) [16,24]. Triethylamine (1.9 mL) and Pd(PPh 3 ) 4 (21 mg, 190 µmol) were added to a solution of the enyne mixture (without the separation of 2a and 2b, 95 mg, 190 µmol, 2a/2b = 1/3) and bromoolefin 3 (81 mg, 230 µmol) in toluene (1.9 mL) at room temperature.…”

“…The only available biological data concern synthetic 1,4α,25D3 and 1,4β,25D3 ligands (Figure 1B) and the results of luciferase reporter assays in transfected human osteosarcoma cells indicate that both isomers are less active than 1,25D3 [15,16]. Interestingly, significant differences in CYP24A1-induced 1,4,25D3 metabolism have been observed between the two isomers, and only the 4α isomer has been shown to be glucuronidated by certain hepatic UGT(s) [16,17]. In addition, 4β,25D3 has been shown to have greater metabolic stability and resistance to CYP24A1 than 4α,25D3 [18].…”

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

“…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. [4][5][6][7] Despite considerable research into vitamin D 3 derivatives, efficient methods for the synthesis of 1β-OH-D 3 and 2β-OH-D 3 are rarely reported. DeLuca's group first reported a facile three-step method for preparation of 1β-OH-D 3 via oxidation of 1α-OH-D 3 , followed by the reduction of the formed 1-oxo-previtamin D 3 and finally by thermal isomerization, to yield the product 1β-…”