Synthesis of Thymidine, Uridine, and 5‐Methyluridine Nucleolipids: Tools for a Tuned Lipophilization of Oligonucleotides. Issue 5 (17th May 2013)

• Record Type: Journal Article
• Authors: Werz, Emma; Viere, Rebecca; Gassmann, Gina; Korneev, Sergei; Malecki, Edith; Rosemeyer, Helmut
• Is Part Of: Helvetica chimica acta. Volume 96:Issue 5(2013:May)
• Page Start: 872
• Page End: 888
• Publication Date: 2013-05-17
• Subjects: Chemistry -- Periodicals; Chemistry, Analytical -- periodicals; Chimie -- Périodiques; 540
• DOI: 10.1002/hlca.201200573
• Languages: English
• ISSNs: 0018-019X

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Three pyrimidine nucleosides, uridine (<bold>1</bold>), 5‐methyluridine (<bold>6</bold>), and 2′‐deoxythymidine (<bold>11</bold>), were converted to amphiphilic nucleolipids. Compounds <bold>1</bold> and <bold>6</bold> were lipophilized by introduction of symmetric ketal moieties with various carbon chain lengths (<italic>i.e.</italic>, 5–17). Two ketal derivatives, <bold>2b</bold> and <bold>7a</bold>, were additionally further hydrophobized by <italic>N</italic>(3)‐farnesylation. 2′‐Deoxythymidine was alkylated at N(3) with a cetyl (=hexadecyl) residue, either directly or, after complete orthogonal protection of the sugar OH groups, by <italic>Mitsunobu</italic> reaction with hexadecan‐1‐ol. Some of the nucleolipids were subsequently converted to their 2‐cyanoethyl phosphoramidites (5′ or 3′), one of which was used for an exemplary synthesis of a lipo‐oligonucleotide. The sequence of this lipo‐oligonucleotide is an encoded manifestation of <italic>Pythagoras</italic>' law, created with a key table in which the letters of the alphabet, the numbers from 0 to 9 as well as the mostly used mathematical symbols are allocated to a ribonucleic acid triplet of the genetic code.</p> </abstract>