Mitsunobu Reactions of 5‐Fluorouridine with the Terpenols Phytol and Nerol: DNA Building Blocks for a Biomimetic Lipophilization of Nucleic Acids. Issue 12 (December 2013)

• Record Type: Journal Article
• Authors: Malecki, Edith; Knies, Christine; Werz, Emma; Rosemeyer, Helmut
• Is Part Of: Chemistry & biodiversity. Volume 10:Issue 12(2013:Dec.)
• Page Start: 2209
• Page End: 2220
• Publication Date: 2013-12
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Biodiversity -- Periodicals; 572
• DOI: 10.1002/cbdv.201300107
• Languages: English
• ISSNs: 1612-1872

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>The cancerostatic 5‐fluorouridine (5‐FUrd; <bold>1</bold>) was sequentially sugar‐protected by introduction of a 2′, 3′‐<italic>O</italic>‐heptylidene ketal group (→<bold>2</bold>), followed by 5′‐<italic>O</italic>‐monomethoxytritylation (→<bold>3</bold>). This fully protected derivative was submitted to <italic>Mitsunobu</italic> reactions with either phytol ((<italic>Z</italic> and <italic>E</italic>)‐isomer) or nerol ((<italic>Z</italic>)‐isomer) to yield the nucleoterpenes <bold>4a</bold> and <bold>4b</bold>. Both were 5′‐<italic>O</italic>‐deprotected with 2% Cl₂CHCOOH in CH₂Cl₂ to yield compounds <bold>5a</bold> and <bold>5b</bold>, respectively. These were converted to the 5′‐<italic>O</italic>‐cyanoethyl phosphoramidites <bold>6a</bold> and <bold>6b</bold>, respectively. Moreover, the 2′, 3′‐<italic>O</italic>‐(1‐nonyldecylidene) derivative, <bold>7a</bold>, of 5‐fluorouridine was resynthesized and labelled at C(5′) with an <italic>Eterneon‐480</italic> fluorophor^® (→<bold>7b</bold>). 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.</p> </abstract>