2-(Acyloxy)ethylphosphonate analogues of prenyl pyrophosphates: synthesis and biological characterization

Synthesis of imidazole-containing analogues of farnesyl pyrophosphate and evaluation of their biological activity on protein farnesyltransferase

“…Reduction of the double bond with magnesium in dry methanol did not afford the desired compound 24 in sufficient yield. This derivative was finally obtained by a SN 2 reaction of the anion of ethyl acetate 22 on farnesyl bromide 23 [26]. Contrary to compounds 13, it was impossible to obtain compound 28 by alkylation of 24 with bromo acetate.…”

“…13 (26): A solution of diethyl 2-(diethoxyphosphoryl)succinate 25 (500 mg, 1.6 mmol, 1.5 equiv.) in anhydrous THF (0.7 mL) was added to a cooled (0°C) suspension of NaH (60% in oil, 155 mg, 3.9 mmol, 1.7 equiv.)…”

Oxygenated N-Acyl Alanine Methyl Esters (NAMEs) from the Marine Bacterium Roseovarius tolerans EL-164

“…After acidification with 2 N HCl to pH 2.0, the solution was extracted with EtOAc (3 × 50 mL). The organic layers were combined, dried with MgSO 4 , and concentrated in vacuo . Column chromatography (SiO 2 , pentane/EtOAc, 10:1) gave the product 15 (0.99 g, 4.36 mmol, 66%) as a yellowish oil: R f (SiO 2 , pentane/EtOAc, 10:1) 0.20; GC (ZB-5 MSi, MSTFA derivative) I 1857; IR (ATR) ν max 3005 (m), 2924 (s), 2855 (s), 2671 (w), 1707 (s), 1460 (m), 1413 (m), 1278 (m), 1227 (m), 935 (m), 725 (m) cm –1 ; 1 H NMR (CDCl 3 , 400 MHz) δ 7.19 (s, 1H, OH), 5.22–5.33 (m, 2H, HCCH), 2.28 (t, 2H, J = 7.7 Hz, CH 2 COOH), 1.92–1.99 (m, 4H, H 2 CHCCHC H 2 ), 1.54–1.61 (m, 2H, CH 2 CH 3 ), 1.13–1.37 (m, 12H, 6 × CH 2 ), 0.81 (t, 3H, J = 7.2 Hz, CH 3 ); 13 C NMR (CDCl 3 , 100 MHz) δ 180.3 (CO), 129.8 (HCCH), 34.1 ( C H 2 COOH), 31.8 (CH 2 ), 29.5 (2 × CH 2 ), 28.9 (2 × CH 2 ), 27.1 (H 2 C HCCH C H 2 ), 24.6 (CH 2 ), 22.6 ( C H 2 CH 3 ), 14.1 (CH 3 ); EIMS m / z (MSTFA derivative) 298 [M] + (21), 283 [M + -CH 3 ] (96), 255 (5), 227 (5), 199 (29), 183 (11), 166 (48), 145 (54), 117 (100), 96 (44), 73 (93), 55 (58), 39 (10).…”

“…The organic layers were combined, dried with MgSO 4 , and concentrated in vacuo. 46 Column chromatography (SiO 2 , pentane/EtOAc, 10:1) gave the product 15 (0.99 g, 4.36 mmol, 66%) as a yellowish oil: R f (SiO 2 , pentane/EtOAc, 10:1) 0.20; GC (ZB-5 MSi, MSTFA derivative) I 1857; IR (ATR) ν max 3005 (m), 2924 (s), 2855 (s), 2671 (w), 1707 (s), 1460 (m), 1413 (m), 1278 (m), 1227 (m), 935 (m), 725 (m) cm −1 ; 1 (5), 227 (5), 199 (29), 183 (11), 166 (48), 145 (54), 117 (100), 96 (44), 73 (93), 55 (58), 39 (10).…”

Synthesis, inhibitory and activation properties of prenyldiphosphate mimics for aromatic prenylations with ubiA-prenyl transferase

“…This methyl phosphonic ester was cleaved with trimethylsilyl bromide in the presence of 2,4,6-collidine as acid scavenger to afford the free hydroxyphosphonic acid 4. 14,15 An attempt to oxidize β-hydroxy phosphonate 3 to the β-keto phosphonate by Doering oxidation failed. Scheme 3.…”