Phosphoramidite → Propargylamine

HRID 552881

反応式

HRID 552881 の反応式
[P:1]([NH2:4])([O-:3])[O-:2].CO[C:7](OC)([O:19][C:20]([C:33]1[CH:38]=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[CH:8]1[CH2:13]CC(CP(=O)([O-])O)CC1.C([NH+:43](CC)CC)C>C(Cl)(Cl)(Cl)Cl>[CH2:13]([NH2:43])[C:8]#[CH:7].[P:1]([NH2:4])(=[O:2])([O-:3])[O:19][CH2:20][C:33]#[CH:38]

参加物

5

反応物 2

HCID 10080320PhosphoramiditeHCID 131728937Triethylammonium [4-(dimethoxytrityloxymethyl)cyclohexyl]methyl Hydrogen Phosphonate

生成物 2

HCID 239041PropargylamineHCID 86630210HCID 86630210、化合物

試薬・触媒・溶媒 1

HCID 5943Carbon Tetrachloride溶媒

実験手順

We first prepared a cyanoethyl-protected dodecathymidine (T12*) on solid support using well established phosphoramidite chemistry (Beaucage, S. L.; Caruthers, M. H. Tetrahedron Lett. 1981, 22, 1859-1862). Then three H-phosphonate diester linkages were introduced using H-phosphonate monoester 1 to yield the modified supported oligonucleotide 2 (FIG. 8). An amidative oxidation with CCl4 in the presence of propargylamine afforded the alkyne-functionalized oligonucleotide 3 with three propargyl phosphoramidate linkages. An aliquot was treated with aqueous ammonia and analyzed by HPLC/MS to determine the efficiency of these synthetic steps (i.e. three H-phosphonate couplings and amidative oxidation). The first H-phosphonate coupling was not complete (86-94%) while the two subsequent couplings were higher yielding. The resulting mixture was composed of 3 (˜75%), unreacted T12 (˜14%) and intermediates with one (˜3%) and two propargyl groups (˜4%) as determined by MALDI-TOF MS analyses.

後処理

  1. customto yield the

出典と根拠

ORDレコード
ord-4d16f6c5492b4b73b5ec4b84a86d611e
出典データセット
uspto-grants-2011_05
特許番号
US07951926B2

関連ノート

読み込み中…