Reaktionsgleichung
C1(=O)OCC=C1.[P:7]([CH2:11][O:12][CH2:13][CH2:14][N:15]1[C:23]2[C:18](=[N:19][CH:20]=[N:21][C:22]=2[NH2:24])[N:17]=[CH:16]1)([OH:10])([OH:9])=[O:8].P([O:29][CH2:30][C@H:31]1[O:35][C@@H:34]([N:36]2[C:45]3[N:44]=[CH:43][N:42]=[C:40]([NH2:41])[C:39]=3[N:38]=[CH:37]2)[C@H:33]([OH:46])[C@@H:32]1[OH:47])(O)(O)=O>>[C@@H:34]1([N:36]2[C:45]3[N:44]=[CH:43][N:42]=[C:40]([NH2:41])[C:39]=3[N:38]=[CH:37]2)[O:35][C@H:31]([CH2:30][OH:29])[C@@H:32]([OH:47])[C@H:33]1[OH:46].[P:7]([CH2:11][O:12][CH2:13][CH2:14][N:15]1[C:23]2[C:18](=[N:19][CH:20]=[N:21][C:22]=2[NH2:24])[N:17]=[CH:16]1)([OH:10])([OH:9])=[O:8]Komponenten
Versuchsvorschrift
Dinucleotide 24 afforded phosphonate 20 and adenosine 5′-monophosphate 21 in about 60% yield. 9-(β-D-Furanosyl)adenine-3′-[[1-(adenin-7-yl-ethoxy)methyl]-phosphonate] gave adenosine (40% yield) and 20 (60% yield). Dinucleotide analog 25, having a butenolide ester unit, was found to be stable to the enzyme.Compound 24, possessing both the skeletons of phosphonate 20 and 5′-adenosine monophosphate 21, was dephosphorylated at the 5′-position by snake venom in 80% yield after 8 h. The resultant 9-(b-D-furanosyl)adenine-3′-[[1-(adenin-7-yl-ethoxy)methyl]phosphonate] was hydrolyzed further in the presence of spleen phosphodiesterase to afford adenosine and phosphonate 20 in about 40-60% yield after 8 h. See, Hakimelahi et al. (1995) J. Med. Chem. 38: 4648-4659 and references cited therein. Spleen phosphodiesterase also degraded compound 24 to give 5′-adenosine monophosphate 21 and phosphonate 20 in an overall yield of 60% after 8 h. These results indicate that the phosphodiesterases recognized dinucleotide analog 24 as a normal substrate. In addition, it was found that nucleotide-containing butenolide 25 was completely resistant to snake venom and spleen enzymes.
Aufarbeitung
- customafter 8 h
Quellen und Nachweise
- ORD-Eintrag
- ord-c485b7f69abe4eb69696dc7984c25ade
- Quelldatensatz
- uspto-grants-2004_11
- Patentnummer
- US06825348B2
Verknüpfte Notizen
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