Nucleotide chemistry. XX. Use of the azido group in the synthesis of 5'-terminal aminodeoxythymidine oligonucleotides

Abstract

ether, affording 504 mg of crude material containing some unreacted starting material. The desired thioether 16 was isolated by column chromatography on silica gel using 30% ether-benzene.To a solution of 367 mg (1.07 mmol) of chromatographed thioether 16 in 5 ml of methylene chloride at 0°was added a solution of 190 mg (1.10 mmoles) of m-chloroperoxybenzoic acid in 5 ml of methylene chloride dropwise over 2.0 min. The solution was stirred for 2.0 hr at 0°and the solvent was removed by distillation at reduced pressure. The residue was taken up in ether and washed with two portions of saturated sodium bicarbonate solution to give the crude sulfoxide 17 as a white foam (276 mg).This material was directly converted to the methylene lactone 10 according to the procedure of Trost and Salzmann.14 A solution of 276 mg (0.77 mmol) of crude sulfoxide 17 in 8.0 ml of toluene was heated at reflux for 4.0 hr. The solution was cooled, diluted with ether, and washed with two portions of saturated sodium bicarbonate solution to afford 175 mg (98%) of crude product. Preparative thin layer chromatography on silica gel using 5% etherbenzene gave 4-deoxydamsin (Rf 0.39) as a white, crystalline solid:

Synthesis of Sphingosine‐1‐phosphonate and Homosphingosine‐1‐phosphonate

“…The same compound could be directly obtained from 3-O-unprotected 16 in a Mitsunobu reaction [27] by activation with (triphenylphosphane)/diisopropyl azodicarboxylate (DIAD) and then reaction with the zinc azideϪpyridine complex [28] in toluene at 50°C, however, in lower overall yield. Liberation of the amino group in 18 by azide reduction with triphenylphosphane in pyridine/water [29] (Ǟ 19), and then O-debenzylation with lithium in liquid ammonia at low temperature, furnished unprotected homosphingosine 20. [16,30] The structural assignment of 20 was supported by per-acetylation affording triacetyl derivative 21, which showed the expected downfield shifts in the 1 H NMR spectrum for 1-H, 3-H, and 4-H.…”

Synthesis and properties of oligonucleotides containing aminodeoxythymidine units

“…We describe in this paper (a) some useful modifications in methods for incorporating 5 Preparation of Dimers I and IV (Solution Phase) Compound IV was prepared in solution and converted to the hydrogen phosphonate (I) as previously described. '5 The properties for Dimer IV are: 3'P NMR (in pyridine-d5), 6 (VIIa) was taken up in anhydrous acetonitrile (6 ml) and treated with 5'-O-trityl-3'-amino-3'-deoxythymidine25 (270 mg, 0.56 mmole) in carbon tetrachloride (6 ml) and triethylamine (1 ml 4.75 (m, lH, H3'), 5.92 (m, lH, Hl'), 6.29 (t, lH, Hl'), 7.82 (s, 1H, H6), 7.85 (s, 1H, H6). Finally, the phosphoramidate salt hydrolyzed cleanly to 3'-aminodeoxythymidine (RP HPLC 9.0 min, positive ninhydrin test) and thymidine 5'-phosphate (RP HPLC 6.7 min) when treated with 80% aqueous acetic acid (16 h, room temp).…”

Oligonucleotides Containing Disaccharide Nucleosides

“…Treatment with PPh 3 followed by alkaline hydrolysis [23] was inconvenient due to the presence of acylprotecting groups in the disaccharide nucleoside 9. The reaction with H 2 S in pyridine [24] [25] was incomplete and resulted in low yield.…”