Tetramethylsuccinimide as a Directing/Protecting Group in Purine Glycosylations

Tetramethylsuccinic anhydride can be used to protect the exocyclic amine of 6-aminopurine derivatives by forming the corresponding tetramethysuccinimide. X-ray crystallography confirms that the imide carbonyl and the methyl groups are positioned to sterically block the N7 nitrogen so that glycosylations occur with very high regiochemical control at N9. This approach is particularly effective for 3-substituted purines where the substituent tends to block access to N9 and inhibit glycosylation at that site.