title: C-C cross-coupling reactions of O6-alkyl-2-haloinosine derivatives and a one-pot cross-coupling/O6-deprotection procedure.
abstract: Reaction conditions for the CC cross-coupling of O(6)-alkyl-2-bromo- and 2-chloroinosine derivatives with aryl-, hetaryl-, and alkylboronic acids were studied. Optimization experiments with silyl-protected 2-bromo-O(6)-methylinosine led to the identification of [PdCl(2)(dcpf)]/K(3)PO(4) in 1,4-dioxane as the best conditions for these reactions (dcpf=1,1'-bis(dicyclohexylphosphino)ferrocene). Attempted O(6)-demethylation, as well as the replacement of the C-6 methoxy group by amines, was unsuccessful, which led to the consideration of Pd-cleavable groups such that C-C cross-coupling and O(6)-deprotection could be accomplished in a single step. Thus, inosine 2-chloro-O(6)-allylinosine was chosen as the substrate and, after re-evaluation of the cross-coupling conditions with 2-chloro-O(6)-methylinosine as a model substrate, one-step C-C cross-coupling/deprotection reactions were performed with the O(6)-allyl analogue. These reactions are the first such examples of a one-pot procedure for the modification and deprotection of purine nucleosides under C-C cross-coupling conditions.
authors.affiliation: Medicinal Chemistry Division, GVK Biosciences Pvt. Ltd. 28A, IDA Nacharam, Hyderabad 500076, Andhra Pradesh, India.
authors.forename: Venkateshwarlu
authors.initials: V
authors.lastname: Gurram
authors.forename: Narender
authors.initials: N
authors.lastname: Pottabathini
authors.forename: Ramesh
authors.initials: R
authors.lastname: Garlapati
authors.forename: Avinash B
authors.initials: AB
authors.lastname: Chaudhary
authors.forename: Balaram
authors.initials: B
authors.lastname: Patro
authors.forename: Mahesh K
authors.initials: MK
authors.lastname: Lakshman
mesh_terms: D002244:Carbon / Q000737:chemistry*; D002384:Catalysis; D056831:Coordination Complexes / Q000737:chemistry; D004146:Dioxanes / Q000737:chemistry; D007288:Inosine / Q000031:analogs & derivatives*; D010165:Palladium / Q000737:chemistry; D011684:Purine Nucleosides / Q000737:chemistry
chemical_list: D056831:Coordination Complexes; D004146:Dioxanes; D011684:Purine Nucleosides; D007288:Inosine; D010165:Palladium; D002244:Carbon; C025223:1,4-dioxane