title: Stereoselective facile synthesis of 2'-spiro pyrimidine pyranonucleosides via their key intermediate 2'-C-cyano analogues. Evaluation of their bioactivity.
abstract: A novel series of 2'-spiro pyrimidine pyranonucleosides has been designed and synthesized. Their precursors, 2'-C-cyano nucleosides 5a,b and 6a,b, were obtained by subjecting 1a,b to the sequence of selective protection of the primary hydroxyl group, acetalation, oxidation, and finally treatment with sodium cyanide. Deoxygenation at the 2'-position of cyanohydrins 5a,b or 6a,b led to the 2'-deoxy derivatives 9a,b. Fully deprotection of 5a,b, 6a,b, and 9a,b gave the desired 2'-C-cyano 7a,b, 8a,b, and 2'-C-cyano-2'-deoxy pyranonucleosides 10a,b, respectively. Mesylation of the corresponding cyanohydrins 5a,b and 6a,b afforded compounds 11a,b and 12a,b which after base treatment and subsequent deprotection furnished the spiro nucleosides 15a,b and 16a. The new analogues were evaluated for their potential cytostatic activities in cell culture.
authors.affiliation: Department of Biochemistry and Biotechnology, Laboratory of Bio-Organic Chemistry, University of Thessaly, 26 Ploutonos Str., 41221 Larissa, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Kiritsis
authors.affiliation: Department of Biochemistry and Biotechnology, Laboratory of Bio-Organic Chemistry, University of Thessaly, 26 Ploutonos Str., 41221 Larissa, Greece.
authors.forename: Stella
authors.initials: S
authors.lastname: Manta
authors.affiliation: Department of Biochemistry and Biotechnology, Laboratory of Bio-Organic Chemistry, University of Thessaly, 26 Ploutonos Str., 41221 Larissa, Greece.
authors.forename: Athina
authors.initials: A
authors.lastname: Dimopoulou
authors.affiliation: Department of Biochemistry and Biotechnology, Laboratory of Bio-Organic Chemistry, University of Thessaly, 26 Ploutonos Str., 41221 Larissa, Greece.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Parmenopoulou
authors.affiliation: Department of Chemistry, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece.
authors.forename: Petros
authors.initials: P
authors.lastname: Gkizis
authors.affiliation: Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.affiliation: Department of Biochemistry and Biotechnology, Laboratory of Bio-Organic Chemistry, University of Thessaly, 26 Ploutonos Str., 41221 Larissa, Greece. Electronic address: dkom@bio.uth.gr.
authors.forename: Dimitri
authors.initials: D
authors.lastname: Komiotis
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011714:Pyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000737:chemistry; D012966:Sodium Cyanide / Q000737:chemistry; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D009705:Nucleosides; D011714:Pyrans; D011743:Pyrimidines; D013141:Spiro Compounds; C030986:pyrimidine; D012966:Sodium Cyanide
keywords: 5-Fluorouracil; C-Cyano pyranonucleosides; Cytostatic agents; Spironucleosides