- An expeditious total synthesis of 50-Deoxy-toyocamycin and 50-Deoxysangivamycin
-
In present paper, an expeditious total synthesis of naturally occurring 50-deoxytoyocamycin and 50-deoxysangivamycin was accomplished. Because of the introduction of a benzoyl group at N-6 of 4-amino-5-cyano-6-bromo-pyrrolo[2,3-d]pyrimidine, a Vorbrüggen glycosylation with 1,2,3-tri-O-acetyl-5-deoxy-β-D-ribofuranose afforded a completely regioselective N-9 glycosylation product, which is unambiguously confirmed by X-ray diffraction analysis. All of the involved intermediates were well characterized by various spectra.
- Dong, Xiangyou,Tang, Jie,Hu, Chen,Bai, Jiang,Ding, Haixin,Xiao, Qiang
-
-
- Synthesis and cytokine modulation properties of pyrrolo[2,3.d]-4- pyrimidone nucleosides
-
A series of pyrrolo[2,3-d]pyrimidone nucleosides were synthesized and evaluated for their ability to enhance Type 2 cytokines and to suppress Type 1 cytokines in human T cells activated in vitro. Compounds 16b, 16c, 16d, 18c, and 19b induced substantial enhancement of IL-4 (a Type 2 cytokine) levels while three compounds (16b, 16c, and 16f) showed significant suppression of IFNγ (a Type 1 cytokine) levels. The results revealed a strict structural requirement for the nucleoside-mediated enhancement of IL- 4. Modifications of the ribofuranose moiety of the nucleosides either abolished or dramatically reduced the activity. Both the 5'-hydroxy and 5- carboxamidine are crucial for the activity. Of the few nucleoside analogues that demonstrated enhancement on Type 2 cytokine production, 7-(β-D- ribofuranosyl)pyrrolo[2,3d]-4-pyrimidone-5-carboxamidine (16c) showed a dramatic enhancement (> 200%) of IL-4 levels and a significant enhancement (36%) of IL-5 levels. Moreover, this compound showed substantial suppression of the Type 1 cytokines, IFNγ (42%), IL-2 (54%), and TNFα (55%). Similarly, compound 16b showed a substantial enhancement of IL-4 (46%) and suppression of IL-2 (35%), IFNγ (30%), and TNFα (26%). To our knowledge, these are the first nucleoside analogues that induce a Type 2 cytokine bias in T cells. The cytokine modulation property of 16c and 16b merits the therapeutic evaluation of these compounds in treating diseases in which immunopathology is associated with polarized Type 1 cytokine responses.
- Wang, Guangyi,Tam, Robert C.,Gunic, Esmir,Du, Jinfa,Bard, Josie,Pai, Bharati
-
p. 2566 - 2574
(2007/10/03)
-
- Deoxy sugar analogues of triciribine: Correlation of antiviral and antiproliferative activity with intracellular phosphorylation
-
Triciribine (TCN) and triciribine monophosphate (TCN-P) have antiviral and antineoplastic activity at low micromolar or submicromolar concentrations. In an effort to improve and better understand this activity, we have conducted a structure - activity rel
- Porcari, Anthony R.,Ptak, Roger G.,Borysko, Katherine Z.,Breitenbach, Julie M.,Vittori, Sauro,Wotring, Linda L.,Drach, John C.,Townsend, Leroy B.
-
p. 2438 - 2448
(2007/10/03)
-