Phosphoramidite → Propargylamine

HRID 552881

Reaktionsgleichung

Reaktionsgleichung von HRID 552881
[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]

Komponenten

5

Edukt 2

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

Produkt 2

HCID 239041PropargylamineHCID 86630210HCID 86630210, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 5943Carbon TetrachlorideLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  1. customto yield the

Quellen und Nachweise

ORD-Eintrag
ord-4d16f6c5492b4b73b5ec4b84a86d611e
Quelldatensatz
uspto-grants-2011_05
Patentnummer
US07951926B2

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