Nucleolipids of the Cancerostatic 5‐Fluorouridine: Synthesis, Adherence to Oligonucleotides, and Incorporation in Artificial Lipid Bilayers. Issue 2 (February 2014)

• Record Type: Journal Article
• Authors: Malecki, Edith; Ottenhaus, Vanessa; Werz, Emma; Knies, Christine; Montilla Martinez, Malayko; Rosemeyer, Helmut
• Is Part Of: Chemistry & biodiversity. Volume 11:Issue 2(2014:Feb.)
• Page Start: 217
• Page End: 232
• Publication Date: 2014-02
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Biodiversity -- Periodicals; 572
• DOI: 10.1002/cbdv.201300127
• Languages: English
• ISSNs: 1612-1872

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>5‐Fluorouridine (<bold>1a</bold>) was converted to its <italic>N(3)</italic>‐farnesylated nucleoterpene derivative <bold>8</bold> by direct alkylation with farnesyl bromide (<bold>4</bold>). Reaction of the cancerostatic <bold>1a</bold> with either acetone, heptan‐4‐one, nonadecan‐10‐one, or hentriacontan‐16‐one afforded the 2′, 3′‐<italic>O</italic>‐ketals <bold>2a</bold>–<bold>2d</bold>. Compound <bold>2b</bold> was then first farnesylated (→<bold>5</bold>) and subsequently phosphitylated to give the phosphoramidite <bold>6</bold>. The ketal <bold>2c</bold> was directly 5′‐phosphitylated without farnesylation of the base to give the phosphoramidite <bold>7</bold>. Moreover, the recently prepared cyclic 2′, 3′‐<italic>O</italic>‐ketal <bold>11</bold> was 5′‐phosphitylated to yield the phosphoramidite <bold>12</bold>. The 2′, 3′‐<italic>O</italic>‐isopropylidene derivative <bold>2a</bold> proved to be too labile to be converted to a phosphoramidite. All novel derivatives of <bold>1a</bold> were unequivocally characterized by NMR and UV spectroscopy and ESI mass spectrometry, as well as by elemental analyses. The lipophilicity of the phosphoramidite precursors were characterized by both their retention times in <italic>RP‐18</italic> HPLC and by calculated log <italic>P</italic> values. The phosphoramidites <bold>6, 7</bold>, and <bold>12</bold> were exemplarily used for the preparation of four terminally lipophilized oligodeoxynucleotides carrying a cyanine‐3 or a cyanine‐5 residue at the 5′‐(<italic>n</italic>–1) position (<italic>i.e.</italic>, <bold>14</bold>–<bold>17</bold>). Their incorporation in an artificial lipid bilayer was studied by single‐molecule fluorescence spectroscopy and fluorescence microscopy.</p> </abstract>