title: The Reactivity of Thymine and Thymidine 5,6-Epoxides with Organometallic Reagents - A Route to Thymidine (6-4) Photoproduct Analogues.
abstract: This report describes an efficient procedure for the generation and isolation of various thymine and thymidine 5,6-epoxides from the corresponding trans-5,6-bromohydrins by reaction with triethylamine. The quantitative isolation of the epoxides, accomplished by solvent precipitation of triethylamine hydrobromide, enabled their regiospecific ring-opening at C6 position by organometallic nucleophiles. The reaction was amenable to a broad range of alkyl, aryl, alkenyl, and alkynyl organomagnesium, -zinc, -aluminum, or -boron reagents, although the reactivity was strongly affected by the electronic effects of N3 protecting group. Additionally, the reaction featured excellent cis-diastereoselectivity providing access to C6-carbon-functionalized dihydrothymidine cis-alcohols, which are synthetic derivatives of UV-induced DNA lesions, namely, thymidine (6-4) photoproducts.
authors.affiliation: Department of Chemistry, †Laboratory of Inorganic Chemistry and ‡Laboratory of Organic Chemistry, University of Helsinki , P.O. Box 55, Helsinki FIN-00014, Finland.
authors.forename: Pauli
authors.initials: P
authors.lastname: Wrigstedt
authors.affiliation: Department of Chemistry, †Laboratory of Inorganic Chemistry and ‡Laboratory of Organic Chemistry, University of Helsinki , P.O. Box 55, Helsinki FIN-00014, Finland.
authors.forename: Jari
authors.initials: J
authors.lastname: Kavakka
authors.affiliation: Department of Chemistry, †Laboratory of Inorganic Chemistry and ‡Laboratory of Organic Chemistry, University of Helsinki , P.O. Box 55, Helsinki FIN-00014, Finland.
authors.forename: Sami
authors.initials: S
authors.lastname: Heikkinen
authors.affiliation: Department of Chemistry, †Laboratory of Inorganic Chemistry and ‡Laboratory of Organic Chemistry, University of Helsinki , P.O. Box 55, Helsinki FIN-00014, Finland.
authors.forename: Martin
authors.initials: M
authors.lastname: Nieger
authors.affiliation: Department of Chemistry, †Laboratory of Inorganic Chemistry and ‡Laboratory of Organic Chemistry, University of Helsinki , P.O. Box 55, Helsinki FIN-00014, Finland.
authors.forename: Minna
authors.initials: M
authors.lastname: Räisänen
authors.affiliation: Department of Chemistry, †Laboratory of Inorganic Chemistry and ‡Laboratory of Organic Chemistry, University of Helsinki , P.O. Box 55, Helsinki FIN-00014, Finland.
authors.forename: Timo
authors.initials: T
authors.lastname: Repo
mesh_terms: D000438:Alcohols / Q000737:chemistry*; D001896:Boron Compounds / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D004852:Epoxy Compounds / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*; D013237:Stereoisomerism; D013936:Thymidine / Q000737:chemistry*; D013941:Thymine / Q000031:analogs & derivatives / Q000737:chemistry*
chemical_list: D000438:Alcohols; D001896:Boron Compounds; D004852:Epoxy Compounds; D009942:Organometallic Compounds; C023963:bromohydrins; D004247:DNA; D013941:Thymine; D013936:Thymidine