Synthesis of 9‐(6‐Deoxy‐α‐L‐Talofuranosyl)‐6‐Methylpurine and 9‐(6‐Deoxy‐β‐D‐Allofuranosyl)‐6‐Methylpurine Nucleosides. Issue 1 (7th April 2020)

• Record Type: Journal Article
• Authors: Hassan, Abdalla E. A.; Abou‐Elkhair, Reham A. I.; Maaroof, Hend M.; Secrist, John A.
• Editors: Beaucage, Serge L.; Bergstrom, Donald E.; Herdewijn, Piet; Matsuda, Akira
• Is Part Of: Current protocols in nucleic acid chemistry. Volume 81:Issue 1(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-04-07
• Subjects: 6‐methylpurine -- D‐allofuranose -- L‐talofuranose -- purine nucleosides -- Vorbrüggen glycosylation; Nucleic acids -- Laboratory manuals; Nucleic Acids -- chemical synthesis; Nucleic acids; Laboratory Manuals; Electronic books; Laboratory manuals; 572.8028
• DOI: 10.1002/cpnc.105
• Languages: English
• ISSNs: 1934-9270

Abstract

Abstract: 6‐Methylpurine (MeP) is a cytotoxic adenine analog that does not exhibit selectivity when administered systemically and could be very useful in a gene therapy approach to cancer treatment involving Escherichia coli purine nucleoside phosphorylase (PNP). 9‐(6‐Deoxy‐β‐D ‐allofuranosyl)‐6‐methylpurine [methyl(allo)‐MePR, 18 ] and 9‐(6‐deoxy‐α‐L ‐talofuranosyl)‐6‐methylpurine [methyl(talo)‐MePR, 21 ] were synthesized as potential prodrugs for MeP in the E. coli PNP/prodrug cancer gene therapy approach. The detailed syntheses of [methyl(allo)‐MePR] and [methyl(talo)‐MePR] are described. The glycosyl donors, 1, 2‐di‐ O ‐acetyl‐3, 5‐di‐ O ‐benzyl‐α‐D ‐allofuranose (12 ) and 1‐ O ‐acetyl‐3‐ O ‐benzyl‐2, 5‐di‐ O ‐benzoyl‐α‐L ‐talofuranose (16 ) were prepared from 1, 2:5, 6‐di‐ O ‐isopropylidene‐α‐D ‐glucofuranose (4 ) in nine and eleven steps, respectively. Vorbrüggen coupling of the latter glycosyl donors with 6‐methylpurine (3 ), followed by deprotection of the sugar hydroxyl groups, gave the title compounds in good overall yields. © 2020 by John Wiley & Sons, Inc. Basic Protocol 1 : Preparation of 6‐methylpurine Basic Protocol 2 : Preparation of the D ‐allofuranose derivative (12 ) Basic Protocol 3 : Preparation of 6‐deoxy‐α‐L ‐talofuranoside Basic Protocol 4 : Preparation of methyl(allo)‐MePR (18 ) Basic Protocol 5 : Preparation of methyl(talo)‐MePR (21 )