- Synthesis and evaluation of 3′-fluorinated 7-deazapurine nucleosides as antikinetoplastid agents
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Kinetoplastid parasites are the causative agents of neglected tropical diseases with an unmet medical need. These parasites are unable to synthesize the purine ring de novo, and therefore rely on purine salvage to meet their purine demand. Evaluating purine nucleoside analogs is therefore an attractive strategy to identify antikinetoplastid agents. Several anti-Trypanosoma cruzi and anti-Trypanosoma brucei 7-deazapurine nucleosides were previously discovered, with the removal of the 3′-hydroxyl group resulting in a significant boost in activity. In this work we therefore decided to assess the effect of the introduction of a 3′-fluoro substituent in 7-deazapurine nucleosides on the anti-kinetoplastid activities. Hence, we synthesized two series of 3′-deoxy-3′-fluororibofuranosyl and 3′-deoxy-3′-fluoroxylofuranosyl nucleosides comprising 7-deazaadenine and -hypoxanthine bases and assayed these for antiparasitic activity. Several analogs with potent activity against T. cruzi and T. brucei were discovered, indicating that a fluorine atom in the 3′-position is a promising modification for the discovery of antiparasitic nucleosides.
- Bouton, Jakob,Caljon, Guy,Furquim d'Almeida, Arno,Hulpia, Fabian,Maes, Louis,Van Calenbergh, Serge
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- Total synthesis of mycalisine B
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The first total synthesis of the marine nucleoside Mycalisine B-a naturally occurring and structurally distinct 4,5-unsaturated 7-deazapurine nucleoside-has been accomplished in 10 linear steps with 27.5% overall yield from commercially available 1,2,3,5-tetra-O-acetyl-ribose and tetracyanoethylene. Key steps of the approach include: (1) I2 catalyzed acetonide formation from 1,2,3,5-tetra-O-acetylribose and acetone at large scale; (2) Vorbrüggen glycosylation using N4-benzoyl-5-cyano-6-bromo-7H-pyrrolo[2,3-d]pyrimidine as a nucleobase to avoid formation of N-3 isomer; (3) mild and scalable reaction conditions.
- Ding, Haixin,Ruan, Zhizhong,Kou, Peihao,Dong, Xiangyou,Bai, Jiang,Xiao, Qiang
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- CD73 INHIBITORS
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Described herein are CD73 inhibitors and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for the treatment of cancer, infections, and neurodegenerative diseases.
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Paragraph 00443
(2018/12/03)
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- A total synthesis of mycalisine A
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In this paper, we report a total synthesis of a naturally occurring pyrrolo[2,3-d]pyrimidine nucleoside, mycalisine A. Our synthetic strategy uses d-xylose as the starting material and Vorbrüggen glycosylation as the key step. Mycalisine A was synthesized in 11 steps with a 15% overall yield.
- Dou, Yan-Hui,Ding, Hai-Xin,Yang, Ru-Chun,Li, Wei,Xiao, Qiang
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p. 379 - 382
(2013/07/04)
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- Synthesis of different 3,5-diazidofuranoses: A new and general synthesis pathway
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Diamino- and diazidofuranoses represent useful precursors, for example, for the synthesis of substituted nucleosides and metal complexes, respectively. Known procedures for their synthesis lack the availability of cheap starting materials, adequate yields, and the access to all possible diastereomeres. Therefore, 3,5-diazido-3,5-dideoxy- and -2,3,5-trideoxyfuranoses both with ribo- and xylo-configuration were prepared using different approaches.
- Koth, Daniel,Fiedler, Andrea,Scholz, Sandy,Gottschaldt, Michael
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p. 267 - 278
(2008/02/12)
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- Aplysia californica mediated cyclisation of novel 3′-modified NAD+ analogues: A role for hydrogen bonding in the recognition of cyclic adenosine 5′-diphosphate ribose
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Cyclic ADP-ribose mobilizes intracellular Ca2+ in a variety of cells. To elucidate the nature of the interaction between the C3′ substituent of cADP-ribose and the cADPR receptor, three analogues of NAD + modified in the adenosine ri
- Mort, Christopher J. W.,Migaud, Marie E.,Galione, Antony,Potter, Barry V. L.
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p. 475 - 487
(2007/10/03)
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- Synthesis of methyl 2-O-allyl-(and 3-O-allyl-)5-O-benzyl-β-D-ribofuranoside
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D-Ribose was converted into methyl 5-O-benzyl-β-D-ribofuranoside and this, on tin-mediated allylation, gave a mixture of the 2-O-allyl and 3-O-allyl derivatives which were separated by chromatography. The more polar isomer was characterised as the 3-O-allyl derivative after conversion via 3-O-allyl-5-O-benzyl-1,2-O-isopropylidene-α-D-ribofuranose (which was also synthesised from 3-O-allyl-1,2:5,6-di-O-isopropylidene-α-D-allofuranose) into the known 5-O-benzyl-1,2-O-isopropylidene-α-D-ribofuranose. Methyl 3-O-allyl-5-O-benzyl-β-D-ribofuranoside was converted into methyl 2-O-allyl-5-O-benzyl-β-D-ribofuranoside via methyl 2-O-allyl-5-O-benzyl-3-O(prop-1-enyl)-β-D-ribofuranoside.
- Desai,Gigg,Gigg
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p. 209 - 221
(2007/10/03)
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- 1,2-Di-O-acetyl-5-O-benzoyl-3-deoxy-3-fluoro-D-xylofuranose. A versatile precursor for the synthesis of 3-deoxy-3-fluoro-β-D-xylofuranosyl nucleosides as potential antiviral agents
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The title compound has been synthesized from D-xylose for use in the preparation of 3-deoxy-3-fluoro-β-D-xylofuranosyl nucleoside analogues and their 2-deoxy derivatives, as exemplified in the guanine and thymine series. The title compound has been synthe
- Gosselin,Puech,Genu-Dellac,Imbach
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- SYNTHESIS OF 9-(3-DEOXY- AND 2,3-DIDEOXY-3-FLUORO-β-D-XYLOFURANOSYL)GUANINES AS POTENTIAL ANTIVIRAL AGENTS
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The first synthesis of the title compounds 8 and 10 was accomplished by a multi-step approach involving prior preparation of a suitably protected fluorosugar 6.
- Puech, Frederic,Gosselin, Gilles,Imbach, Jean-Louis
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p. 3171 - 3174
(2007/10/02)
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- REGIOSELECTIVE O-DEACYLATION OF FULLY ACYLATED GLYCOSIDES AND 1,2-O-ISOPORPYLIDENEALDOFURANOSE DERIVATIVES WITH HYDRAZINE HYDRATE
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On hydrazinolyis in 1:4 acetic acid-pyridine, and in pyridine, partisl O-deacylation of fully acylated methyl glycosides and some other glycosyl compounds ( 23 compounds ) was found to be induced, to give, in good yields, products bearing one free hydroxy
- Ishido, Yoshiharu,Sakairi, Nobuo,Sekiya, Masao,Nakazaki, Nobuo
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