ChemInform Abstract: Synthesis of 1,7‐Dideaza‐2′‐deoxyadenosine and Related Pyrrolo(2,3‐b)pyridine 2′‐Deoxy‐β‐D‐ribonucleosides: Stereoselective Phase‐Transfer Glycosylation via the Nucleobase Anion.

Seela, Frank; Gumbiowski, R.

doi:10.1002/chin.198942322

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“…To the best of our knowledge, this is the first extensive report on a practical glycosylation protocol for substituted pyrrolo [2,3-b]pyridines under Vorbruggen reaction conditions. Previous studies only concerned two substrates, 19 employed anion glycosylation 20 or acid-catalyzed fusion. 21 We initially envisioned to substitute the 4-chlorine of 45 with sodium azide, but found that this could only be effected at 110 °C in the presence of 15-crown-5.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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Discovery of Pyrrolo[2,3-b]pyridine (1,7-Dideazapurine) Nucleoside Analogues as Anti-Trypanosoma cruzi Agents

et al. 2019

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Trypanosoma cruzi is the causative pathogen of Chagas disease and the main culprit for cardiac-related mortality in Latin-America triggered by an infective agent. Incapable of synthesizing purines de novo, this parasite depends on acquisition and processing of host-derived purines, making purine (nucleoside) analogues a potential source of antitrypanosomal agents. In this respect, hitherto 7-deazaadenosine (tubercidin) analogues attracted most attention. Here, we investigated analogues with an additional nitrogen (N1) removed. Structure−activity relationship investigation showed that C7 modification afforded analogues with potent antitrypanosomal activity. Halogens and small, linear carbon-based substituents were preferred. Compound 11 proved most potent in vitro, showed full suppression of parasitemia in a mouse model of acute infection, and elicited 100% animal survival after oral dosing at 25 mg/kg b.i.d. for 5 and 15 days. Cyclophosphamide-induced immunosuppression led to recrudescence. Washout experiments demonstrated a lack of complete clearance of infected cell cultures, potentially explaining the in vivo results.

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Section: ■ Results and Discussionmentioning

confidence: 99%

“…HRMS (ESI): calcd for C 14 H 16 N 3 O 4 ([M + H] + ), 290.1135; found, 290.1121. 3-Phenylethynyl-4-amino-N1-(β-D-ribofuranosyl)-pyrrolo[2,3-b]pyridine(20). 11 (0.16 g, 0.4 mmol, 1 equiv) was added to a 10 mL round bottom flask, after which CuI (0.015 g, 0.080 mmol, 0.2 equiv), h i b i t e d .…”

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confidence: 99%