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Publications (5)4.55 Total impact

  • ChemInform 04/2005; 36(15). DOI:10.1002/chin.200515200
  • Simon Eppacher · Markus Christen · Andrea Vasella
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    ABSTRACT: The D-allo- and L-talo-hept-6-ynofuranosyluracil-derived phosphoramidites 11A and 11T were prepared in 9–10% yield over eight steps from the previously described propargylic alcohols 1A and 1T, respectively. The corresponding nucleotides were incorporated into rU14 by standard solid-phase synthesis. While the duplex consisting of rU14 with one L-talo-hept-6-ynofuranosyluracil in the middle of the strand and rA14 (IV) had the same melting point as the reference duplex rU14rA14 (III), the duplex with one D-allo-hept-6-ynofuranosyluracil in the middle of rU14 and rA14 (IIII) melted 1.5° lower than the reference duplex. The duplex IVI consisting of rU14 with six L-talo-hept-6-ynofuranosyluracils distributed over the entire strand and rA14 showed a melting point that is 11° lower than the reference duplex. The corresponding duplex IIV of rU14 possessing six D-allo-hept-6-ynofuranosyluracils and rA14 showed a melting point which is more than 20° below the one of the reference duplex. These results are in qualitative agreement with the predictions based on the conformational analysis of the nucleosides and the interference of the ethynyl moiety with the hydration of the oligonucleotides.
    Helvetica Chimica Acta 12/2004; 87(12):3004 - 3020. DOI:10.1002/hlca.200490271 · 1.14 Impact Factor
  • Simon Eppacher · Bruno Bernet · Andrea Vasella
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    ABSTRACT: A linear and a convergent synthesis of uridine-derived backbone-base-dedifferentiated (backbone including) oligonucleotide analogues were compared. The Sonogashira cross-coupling of the alkyne 1 and the iodide 2 gave the dimer 4 that was C-desilylated and again coupled with 2 to give the trimer 6 (Scheme 1). Repeating this linear sequence led to the pentamer 10. Coupling yields were satisfactory up to formation of the trimer 6, but decreased for the coupling to higher oligomers. Similarly, coupling of the alkynes 5, 7, and 9 with the iodouridine 3 gave, in decreasing yields, the trimer 12, tetramer 13, and pentamer 14, respectively. The dimeric iodouracil 20 was synthesized by coupling the alkyne 17 with the iodide 16 to the dimer 18, followed by iodination at C(6/I) to 19 and O-silylation (Scheme 2). The iodinated dimer 23 was prepared by iodinating and O-silylating the known dimer 21. Coupling of 20 and 23 with the dimer 5, trimer 7, and tetramer 9 gave the tetramers 8 and 13, the pentamers 10 and 14, and the hexamer 15, respectively (Scheme 3). The oligomers up to the pentamer 14 were deprotected to provide the trimer 24, tetramer 25, and pentamer 26 (Scheme 4). There was no evidence for the heteropairing of the pentamer 26 and rA7 , nor for the pairing of rU5 and rA7, while a UV melting experiment showed the beginning of a sigmoid curve for the interaction of rU7 with rA7. Therefore, the pentamer 26 does not pair more strongly with rA7 than rU5.
    Helvetica Chimica Acta 11/2004; 87(12):2969-2986. DOI:10.1002/hlca.200490269 · 1.14 Impact Factor
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    ABSTRACT: In contradistinction to the corresponding Grignard reagent, bis[(trimethylsilyl)ethynyl]zinc reacted with the 5'-oxoadenosine 3 diastercoselectively to the beta-D-allo-hept-6-ynofuranosyladenine 5. Lithiation/iodination of the monomeric propargyl alcohol 5 and of the dimeric propargyl alcohol 22 provided the 8-iodoadenosines 7 and 18, respectively, considerably shortening the synthesis of the dimeric O-silylated 8-iodoadenosine 25. The mixed uridine- and adenosine-derived tetramers 21 and 32 were synthesised. The tetramer 21 was prepared by a linear sequence. Sonogashira coupling of 9 and 13 yielded the trimer 16 that was C-desilylated to 17 A second Sonogashira coupling of 17 and 19 yielded the tetramer 21. Tetramer 32 was prepared in higher yields by a convergent route, coupling the acetylene 29 and the iodide 30. The uridine-derived iodides proved more reactive than the adenosine-derived analogues, and the N-6-unprotected adenosine-derived alkynes were more reactive than their N-6-benzoylated analogues
    Helvetica Chimica Acta 01/2004; 87:2969-2986. · 1.14 Impact Factor
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    ABSTRACT: A new type of oligonucleosides has been devised to investigate the potential of oligonucleosides with a nucleobase-including backbone to form homo- and/or heteroduplexes (cf. Fig. 2). It is characterised by ethynyl-linkages between C(5′) and C(6) of uridine, and between C(5′) and C(8) of adenosine. Force-field calculations and Maruzen model studies suggest that such oligonucleosides form autonomous pairing systems and hybridize with RNA. We describe the syntheses of uridine-derived monomers, suitable for the construction of oligomers, and of a dimer. Treatment of uridine-5′-carbaldehyde (2) with triethylsilyl acetylide gave the diastereoisomeric propargylic alcohols 6 and 7 (1 : 2, 80%; Scheme 1). Their configuration at C(5′) was determined on the basis of NOE experiments and X-ray crystal-structure analysis. Iodination at C(6) of the (R)-configured alcohol 7 by treatment with lithium diisopropylamide (LDA) and N-iodosuccinimide (NIS) gave the iodide 17 (62%), which was silylated at O−C(5′) to yield 18 (89%; Scheme 2). C-Desilylation of 7 with NaOH in MeOH/H2O led to the alkyne 10 (98%); O-silylation of 10 at O−C(5′) gave 16 (84%). Cross-coupling of 18 and 16 yielded 63% of the dimer 19, which was C-desilylated to 20 in 63% yield. Cross-coupling of 10 and the 6-iodouridine 13 (70%), followed by treatment of the resulting dimer 14 with HF and HCl in MeCN/H2O, gave the deprotected dimer 15 (73%).
    Helvetica Chimica Acta 07/2000; 83(7):1311 - 1330. DOI:10.1002/1522-2675(20000705)83:7<1311::AID-HLCA1311>3.0.CO;2-2 · 1.14 Impact Factor