501431-56-7

Upstream product

• 114694-12-1 (5Z,7E)-(1S,3R,20S)-1,3-bis<(tert-butyldimethylsilyl)oxy>-9,10-seco-22,23-dinor-5,7,10(19)-cholatrien-24-ol 
• 75-16-1 methylmagnesium bromide 
• 501431-51-2 ethyl (5Z,7E,23aE)-(1S,3R)-1,3-bis[(t-butyldimethylsilyl)oxy]-22-phenylsulfonyl-23-hydroxy-23a-methyl-23a,23b-dihomo-9,10-secochola-5,7,10⁽¹⁹⁾,23-tetraene-24-oate 
• 223538-02-1 (5Z,7E)-(1S,3R)-1,3-bis[(t-butyldimethyl-silyl)oxy]-24-phenylsulfonyl-22,23-dinor-9,10-secochola-5,7,10⁽¹⁹⁾-triene 
• 114694-13-2 (5Z,7E)-(1S,3R,20S)-1,3-bis<(tert-butyldimethylsilyl)oxy>-9,10-seco-22,23-dinor-5,7,10(19)-cholatrienol 22-p-toluenesulfonate 
• 18162-48-6 tert-butyldimethylsilyl chloride 
• 501431-52-3 (5Z,7E,24E)-(1S,3R)-1,3-bis[(t-butyldimethylsilyl)oxy]-22-phenylsulfonyl-24-methyl-24a-homo-9,10-secocholesta-5,7,10⁽¹⁹⁾,24-tetraen-23,25-diol 

Relevant academic research and scientific papers

Synthesis and evaluation of geometric analogs of 1α,25-dihydroxyvitamin D2 as potential therapeutics

An improved convergent strategy was developed for the synthesis of the previously obtained side-chain extended and rigidified analogs of 1α,25-dihydroxyvitamin D2, PRI-1906 and PRI-1907. New (24Z) geometric isomers of the analogs, PRI-1916 and PRI-1917, were also obtained and identified. These side-chain isomers were separable by flash chromatography, as C-25 alcohols, from the synthetic precursors of PRI-1906 and PRI-1907, respectively. The structures of new analogs were determined by advanced techniques of 1H and 13C NMR, including COSY, HSQC and HMBC sequences. Binding affinities of the geometric analogs PRI-1906 and PRI-1916 and their respective C-26, C-27 homologs PRI-1907 and PRI-1917 for the full-length human vitamin D receptor were determined by a fluorescence polarization competition assay. The binding affinity of (24Z) methyl analog PRI-1906 was much higher than that of (24E) analog PRI-1906, while the affinity of (24Z) ethyl analog PRI-1917 was lower than that of the respective PRI-1907. Investigation of the metabolism of these compounds by human CYP24A1 revealed they are much more resistant to CYP24A1 than 1α,25-dihydroxyvitamin D2, indicating they could have longer-term biological effects on target tissues.

Synthesis and antiproliferative activity of side-chain unsaturated and homologated analogs of 1,25-dihydroxyvitamin D(2). (24E)-(1S)-24-Dehydro-24a-homo-1,25-dihydroxyergocalciferol and congeners.

A series of analogs of 1,25-dihydroxyergocalciferol (1-4) was synthesized and screened for their antiproliferative activity in vitro. The structure of new analogs was designed based on biological activity of the previously obtained side-chain modified analogs of vitamin D(2) and D(3). The analogs were obtained by the Julia olefination of C(22)-vitamin D sulfone 11 with side-chain aldehyde 15. The analogs were tested for their antiproliferative activity against the cells of human breast cancer lines T47D and MCF7 as well as human and mouse leukemia lines, HL-60 and WEHI-3, respectively. Analog 2 (PRI-1907) showed the strongest antiproliferative activity out of the present series of analogs of 1,25-dihydroxyvitamin D(2) with the mono homologated and double unsaturated side chain. The activity of 2 was 3-150 times stronger, depending on the cell line, than that of 1,25-dihydroxycholecalciferol (calcitriol), used as standard. Copyright 2002 Elsevier Science Inc.