title: Mitsunobu reactions of 5-fluorouridine with the terpenols phytol and nerol: DNA building blocks for a biomimetic lipophilization of nucleic acids.
abstract: The cancerostatic 5-fluorouridine (5-FUrd; 1) was sequentially sugar-protected by introduction of a 2',3'-O-heptylidene ketal group (→2), followed by 5'-O-monomethoxytritylation (→3). This fully protected derivative was submitted to Mitsunobu reactions with either phytol ((Z and E)-isomer) or nerol ((Z)-isomer) to yield the nucleoterpenes 4a and 4b. Both were 5'-O-deprotected with 2% Cl2 CHCOOH in CH2 Cl2 to yield compounds 5a and 5b, respectively. These were converted to the 5'-O-cyanoethyl phosphoramidites 6a and 6b, respectively. Moreover, the 2',3'-O-(1-nonyldecylidene) derivative, 7a, of 5-fluorouridine was resynthesized and labelled at C(5') with an Eterneon-480 fluorophor(®) (→7b). The resulting nucleolipid was studied with respect to its incorporation in an artificial bilayer, as well as to its aggregate formation. Additionally, two oligonucleotides carrying terminal phytol-alkylated 5-fluorouridine tags were prepared, one of which was studied concerning its incorporation in an artificial lipid bilayer.
authors: Organic Materials Chemistry and Bioorganic Chemistry, Institute of Chemistry of New Materials, University of Osnabrück, Barbarastrasse. 7, D-49069 Osnabrück.
authors: Edith
authors: E
authors: Malecki
authors: Christine
authors: C
authors: Knies
authors: Emma
authors: E
authors: Werz
authors: Helmut
authors: H
authors: Rosemeyer
mesh_terms: D000080462:Acyclic Monoterpenes; D001672:Biocompatible Materials / Q000737:chemistry* / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D007536:Isomerism; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D009841:Oligonucleotides / Q000737:chemistry / Q000378:metabolism; D010836:Phytol / Q000737:chemistry*; D013729:Terpenes / Q000737:chemistry*; D014529:Uridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D000080462:Acyclic Monoterpenes; D001672:Biocompatible Materials; D008051:Lipid Bilayers; D009841:Oligonucleotides; D013729:Terpenes; D010836:Phytol; C001943:5-fluorouridine; D004247:DNA; C007836:geraniol; D014529:Uridine
keywords: Lipophilization; Mitsunobu reaction; Nerol; Nucleolipids; Phytol; Uridine, 5-fluoro-