title: Regioselective 1-N-Alkylation and Rearrangement of Adenosine Derivatives.
abstract: Several methods for the preparation of some N(6)-substituted adenosines based on selective 1-N-alkylation with subsequent Dimroth rearrangement were developed. The proposed methods seem to be effective for the preparation of natural N(6)-isopentenyl- and N(6)-benzyladenosines, which are known to possess pronounced biological activities. Direct 1-N-alkylation of 2',3',5'-tri-O-acetyladenosine and 3',5'-di-O-acetyl-2'-deoxyadenosine with alkyl halides in N,N-dimethylformamide (DMF) in the presence of BaCO3 and KI gave 1-N-substituted derivatives with quantitative yields, whereas 1-N-alkylation of adenosine was accompanied by significant O-alkylation. Moreover, the reaction of trimethylsilyl derivatives of N(6)-acetyl-2',3',5'-tri-O-acetyladenosine and N(6)-acetyl-3',5'-di-O-acetyl-2'-deoxyadenosine with alkyl halides leads to the formation of the stable 1-N-substituted adenosines. Dimroth rearrangement of 1-N-substituted adenosines in aqueous ammonia yields pure N(6)-substituted adenosines.
authors.affiliation: a Engelhardt Institute of Molecular Biology , Russian Academy of Sciences , Moscow , Russian Federation.
authors.forename: Vladimir E
authors.initials: VE
authors.lastname: Oslovsky
authors.forename: Mikhail S
authors.initials: MS
authors.lastname: Drenichev
authors.forename: Sergey N
authors.initials: SN
authors.lastname: Mikhailov
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry; D000478:Alkylation; D003839:Deoxyadenosines / Q000737:chemistry*
chemical_list: D003839:Deoxyadenosines; C025325:2',3',5'-tri-O-acetyladenosine; D000241:Adenosine
keywords: 1-N-substituted adenosines; Dimroth rearrangement; N6-substituted adenosines; TMS derivatives; alkylation; regioselectivity