Design and efficient synthesis of new stable 1α,25-dihydroxy-19-norvitamin D3 analogues containing amide bond

Synthesis and Structure-Activity Relationship Study of 1,12-Dicarba-closo-dodecaborane-based Triol Derivatives as Nonsecosteroidal Vitamin D Analogs

“…Suhara et al also reported that introduction of an amide group as the linking moiety in secosteroid derivatives resulted in the complete loss of activity. 12 The rigid nature of the amide substructure may prevent the molecule from adopting a suitable conformation for binding to the receptor.…”

Synthetic Approaches to Phosphasugars (2-oxo-1,2-oxaphosphacyclanes) Using the Anomeric Alkoxyl Radical β-Fragmentation Reaction as the Key Step

“…To a solution of 1- O -benzoyl-2,3- O -isopropylidene-α- d -mannofuranose 25 (188 mg, 0.58 mmol) in dry DMF (2 mL) were added imidazole (79 mg, 1.16 mmol), DMAP (1 mg, 0.008 mmol), and TBDPSiCl (200 μL, 0.769 mmol) at room temperature under nitrogen. The mixture was then stirred for 2 h, poured into water, and extracted with CH 2 Cl 2 .…”

“…A solution of 5 (8.5 mg, 0.014 mmol) in NaOEt/EtOH 0.01 M (0.12 mL, 1.2 × 10 −3 mmol) was stirred at room temperature under nitrogen for 24 h. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Chromatotron chromatography (hexanes−EtOAc, 40:60) to give compound 38 (5.2 mg, 0.01 mmol, 70%) as a crystalline solid: mp 134.4−135.6 °C (from n-hexane− EtOAc); [α] D +11.9 (c, 0.27, CHCl 3 ); IR (CHCl 3 ) 2996, 1428, 1243, 1229, 1113 cm −1 ; 1 H NMR (500 MHz, CDCl 3 , simulated coupling constants using DAISY) δ H 1.07 (9H, s), 1.37 (3H, s), 1.39 (3H, s), 2.36 (1H, ddd, 2 J PH = 17.8 Hz, J = 16.3, 4.5 Hz, H2α), 2.59 (1H, ddd, 2 J PH = 7.9 Hz, J = 16.3, 4.5 Hz, H2β), 3.96 (1H, dd, J = 9.8, 6.0 Hz, H6a), 4.05 (1H, dd, J = 9.8, 7.6 Hz, H6b), 4.52 (1H, ddd, 3 J PH = 0.8 Hz, J = 6.9, 1.9 Hz, H4), 4.72 (1H, dddd, 3 J PH = 6.3 Hz, J = 7.6, 6.0, 1.9 Hz, H5), 4.81 (1H, dddd, 3 J PH = 24.6 Hz, J = 6.9, 4.5, 4. (39). A solution of 6 (4.8 mg, 0.0079 mmol) in NaOEt/EtOH 0.01 M (0.07 mL, 0.7 × 10 −3 mmol) was stirred at room temperature under nitrogen for 24 h. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Chromatoron chromatography (hexanes−EtOAc, 40:60) to give 39 (3.2 mg, 6.0 × 10 3 mmol, 75%) as a crystalline solid: mp 171.8−173.2 °C (from n-hexane−EtOAc); [α] D +10.8 (c, 0.12, CHCl 3 ); IR (CHCl 3 ) 2997, 1229, 1113 cm −1 ; 1 H NMR (500 MHz, CDCl 3 , simulated coupling constants using DAISY) δ H 1.08 (9H, s), 1.35 (3H, s), 1.63 (3H, s), 2.11 (1H, ddd, 2 J PH = 6.6 Hz, J = 15.9, 4.0 Hz, H2α), 2.62 (1H, ddd, 2 J PH = 14.8 Hz, J = 15.9, 4.…”

Recent Results on A-Ring Modification of 1α,25-Dihydroxyvitamin D3: Design and Synthesis of VDR-Agonists and Antagonists with High Biological Activity

“…Analogs of 19-nor-1, prepared by replacing C5-C6 with an amide function and C2 with hydroxy and hydroxypropoxy groups as in 48a-c, did not bind to the VDR, even at a high concentrations [116].…”