Liquid–liquid and solid–liquid phase-transfer glycosylation of pyrrolo[2,3-d]pyrimidines: stereospecific synthesis of 2-deoxy-β-D-ribofuranosides related to 2′-deoxy-7-carbaguanosine

Abstract

The yield of phase-transfer glycosylation of 2-amino-4-methoxy-7H-pyrrolo[2,3-d]pyrimidine (3b) with 2-deoxy-3,5-di-O-(p-toluoyl)-α-D-erythro-pentofuranosyl chloride (4) is limited under liquid–liquid conditions (50% aq. NaOH, CH₂Cl₂, Bu₄NHSO₄) due to deprotection of alkali-labile protecting groups in the halogenose (4). Application of more lipophilic 2-amino-4-alkoxypyrrolo[2,3-d]pyrimidines such as compounds (3d) or (3e) decreases side reactions to some extent. To overcome these difficulties solid–liquid phase-transfer glycosylation employing an aprotic solvent, solid KOH, and the cryptand tris[2-(2-methoxyethoxy)ethyl]amine (TDA-1) has been developed. The new glycosylation method leads stereospecifically in high yield to 2-amino-4-alkoxy-(7a–c) or 2-amino-4-chloro-7H-pyrrolo[2,3-d]pyrimidine 2-deoxy-β-D-erythro-pentofuranosides (8b) which can be converted into 2′-deoxy-7-carbaguanosine (1) or other 7-carbapurine 2′-deoxy-erythro-pentofuranosides (‘2′-deoxyribonucleosides’).