A new route to some enantiomerically pure substituted morpholines from d-ribono- and d-gulono-1,4-lactones

Discovery and Structure–Activity Relationships of Novel Template, Truncated 1′-Homologated Adenosine Derivatives as Pure Dual PPARγ/δ Modulators

“…Protection of the primary hydroxyl group of 20 with trityl (Tr) followed by reduction with NaBH 4 afforded the diol 21 . Regioselective tosylation of the primary alcohol of 21 smoothly converted the mono tosylate into 4-oxo sugar 22 . Removal of the Tr group of 22 was achieved by treating with Et 2 AlCl in CH 2 Cl 2 at −40 °C to produce the glycosyl donor 23 .…”

“…Found: C,39.52;H,3.35;N,13.58;S,6. 1, 152.3, 148.9, 142.9, 141.0, 135.7, 135.3, 130.4, 126.6, 118.9, 94.7, 76.8, 73.5, 48.7, 46.8, 42.2, 32.8 4.83;N,18.65;S,8.54. Found: C,54.32;H,4.96;N,18.77;S,8. 21). To a stirred solution of 20 (2.01 g, 10.56 mmol) in pyridine (36 mL, 0.3 M) were added trityl chloride (3.24 g, 11.62 mmol) and 4-dimethylaminopyridine (258 mg, 2.11 mmol) at 0 °C, and the mixture was stirred with heating at 80 °C under a N 2 atmosphere.…”

“…The residue was purified by flash silica gel column chromatography (n-hexanes/EtOAc = 8:1) to give 7 (453.0 mg, 78%) as a syrup: 1 H NMR (CDCl 3 , 400 MHz): δ 4.92 (dt, J = 1.8, 5.6 Hz, 1H), 4.72 (dd, J = 2.0, 6.0 Hz, 1H), 4.26−4.30 (m, 1H), 4.04 (s, 1H), 3.79 (t, J = 3.8 Hz, 1H), 3.31−3.32 (m, 1H), 3.19 (dd, J = 5.4, 12.0 Hz, 1H), 2.84 (dd, J = 1.6, 12.0 Hz, 1H), 1.51 (s, 3H), 1.43 (s, 3H), 1.32 (dd, J = 8.4 Hz, 6 H); 13 C NMR (CDCl 3 ): δ 111. 5, 109.8, 87.3, 84.0, 78.0, 68.3, 56.3, 56.2, 38.8, 26.8, 26.3, 25.8, 24.9; [α] (8). A solution of 7 (21.78 g, 83.66 mmol) in 60% aqueous AcOH (250 mL) was stirred at rt for 2 h. The reaction mixture was evaporated under reduced pressure, and the resulting residue was purified by flash silica gel column chromatography (nhexanes/EtOAc = 1:2) to give the diol 8 (14.85 g, 81%) as a white solid, and 6.15 g of the starting material 13 was recovered after being repeated for three times: mp 100.7−101.8 °C; 1 H NMR (CDCl 3 , 400 MHz): δ 4.93 (dt, J = 1.8, 5.6 Hz, 1H), 4.76 (dd, J = 2.0, 5.6 Hz, 1H), 3.76−3.80 (m, 1H), 3.70−3.74 (m, 1H), 3.64−3.68 (m, 1H), 3.40 (dd, J = 1.6, 5.2 Hz, 1H), 3.16 (dd, J = 5.0, 12.8 Hz, 1H), 2.90 (dd, J = 1.6, 12.8 Hz, 1H), 1.52 (s, 3H), 1.33 (s, 3H); 13 C NMR (CDCl 3 , 100 MHz): δ 111.6, 87.…”

“…40−7.46 (m, 6 H), 7.28−7.34 (m, 6 H), 7.22−7.28 (m, 3H), 4.29−4.36 (m, 1H), 4.10 (dd, J = 5.8, 9.6 Hz, 1H), 3.70−3.90 (m, 3H), 3.47 (dd, J = 3.0, 9.8 Hz, 1H), 3.31 (dd, J = 6.8, 9.8 Hz, 1H), 3.01 (dd, J = 5.0, 8.7 Hz, 1H), 2.89 (d, J = 3.9 Hz, 1H), 1.309 (s, 3H), 1.30 (s, 3H); 13 C NMR (CDCl 3 , 100 MHz): δ 149. 8,147.6,143.6,135.9,128.6,127.9,127.2,123.7,108.5,87.1,69.0,65.0,60.7,27.8,25.3;Anal. Calcd for C 27 H 30 O 5 : C,74.63;H,6.96.…”

Chemoselective Synthesis of β-Ketophosphonates Using Lithiated α-(Trimethylsilyl)methylphosphonate

“…5-{[(3aR,4R,6aR)-2,2-dimethyl-6-oxo-tetrahydro-2H-furo [3,4-d]- [1,3]dioxol-4-yl]methoxy}-5-oxopentanoic Acid (5m). To a solution of 2,3-O-isopropylidene-D-ribono-1,4-lactone 28 (720 mg, 3.83 mmol, 1 equiv) and glutaric anhydride (873 mg, 7.65 mmol, 2 equiv) in CH 2 Cl 2 (8 mL) were added Et 3 N (1.07 mL, 7.65 mmol, 2 equiv) and DMAP (47 mg, 0.38 mmol, 0.1 equiv). The mixture was stirred overnight at rt and acidified to pH 1−2 with a 1 M HCl solution, and CH 2 Cl 2 was added.…”