Abstract
The electrophilic fluorination of 4‐chloropyrrolo[2,3‐d]pyrimidine (1) was studied culminating a 59% conversion of compound 1 to 4‐chloro‐5‐fluoropyrrolo[2,3‐d]pyrimidine (2) using Selectfluor. This transformation proceeded via the 4‐chloro‐5,6‐dihydro‐5‐fluoro‐6‐hydroxypyrrolo[2,3‐d]pyrimidine (3) in a 9:1 trans:cis ratio. The trans isomer of compound 3 was studied by 1H NMR and 19F NMR, and the 5‐H tautomer (4) was observed as another intermediate. A modified Vorbruggen procedure of compound 2 and tetra‐O‐acetylribose gave 4‐chloro‐5‐fluoro‐7‐(2,3,5,‐tri‐O‐benzoyl‐β‐d‐ribofuranosyl)pyrrolo[2,3‐d]pyrimidine (6) in a 65% yield. Treatment of compound 6 with ammonia (l) in dioxane gave 5‐fluorotubercidin (7). No antibacterial activity was observed. An MTT assay (Promega) against Huh‐7 liver cells, normal mouse spleen cells stimulated with Con A (a T‐cell mitogen), and normal mouse spleen stimulated with LPS (a B‐cell mitogen) showed no significant toxicity. Increased activity of 7 over tubercidin was observed against L‐1210 cells and toxicity in fibroblast cells was reduced.
†In honor and celebration of the 70th birthday of Professor Leroy B. Townsend.
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Acknowledgments
Dr. Swayze and Dr. Migawa thank Prof. Leroy B. Townsend for his mentorship and guidance, and are grateful for the lessons in life and science that were learned in his laboratory. We also thank Lisa Risen for the T/T and MIC experiments.
Notes
†In honor and celebration of the 70th birthday of Professor Leroy B. Townsend.