Biomedical subjects

Lise Keinicke

Publications and source records attributed to Lise Keinicke.

6 recordsLinked to original sources

PubMed2005

Nonradical zinc-Barbier reaction for diastereoselective synthesis of vicinal amino alcohols.

A new protocol for the synthesis of vicinal amino alcohols is described. The method employs a Barbier-type reaction between an imine and 3-benzoyloxyallyl bromide in the presence of zinc metal. The addition products are debenzoylated to afford amino alcohols in good yields and with diastereomeric ratios greater than 85:15 in favor of the anti isomer. A Hammett study has been performed which strongly indicates that the allylation does not follow a radical mechanism, but instead an organometallic reagent is formed which subsequently reacts with the imine. A computational study based on this mechanism reproduces the observed diastereoselectivity with high accuracy, but only when a sufficiently large portion of the substrate is included.

Journal Article↗

PubMed2005

A concise synthetic route to the conduritols from pentoses.

A short synthetic strategy for preparation of the conduritols is described. The key step employs a zinc-mediated fragmentation of protected methyl 5-deoxy-5-iodo-d-pentofuranosides followed by an allylation of the intermediate aldehyde in the same pot. The allylation is performed with 3-bromopropenyl benzoate and occurs with good diastereoselectivity. An amino group can be introduced in the product by trapping the intermediate aldehyde as the imine prior to the allylation. The functionalised 1,7-octadienes, thus obtained, are converted into protected conduritols by ring-closing olefin metathesis.

Cyclization↗

PubMed2005

Combinatorial libraries - from solution to 2D microarrays.

Enzymatic modifications of split and mix libraries were followed by "pulling down" onto a 2-dimensional DNA microarray, via PNA tagging; this allowed complete library interrogation of all members of the split and mix library.

Combinatorial Chemistry Techniques↗

PubMed2003

2'-Spiro ribo- and arabinonucleosides: synthesis, molecular modelling and incorporation into oligodeoxynucleotides.

We have synthesized four conformationally restricted bicyclic 2'-spiro nucleosides via 2'-C-allyl nucleosides as key intermediates. The ribo-configured 2'-spironucleosides 9b and 14b were obtained by a convergent strategy starting from 2-ketofuranose 1 whereas the arabino-configured 2'-spironucleosides 21 and 27 were obtained by a linear strategy with a 2'-ketouridine derivative as starting material. The furanose ring of 9b/14b adopts N-type conformations whereas the furanose ring of 21/27 exists as an N<==>S equilibrium. These compounds showed no anti-HIV-1 activity or cytotoxicity. Incorporation of the four 2'-spironucleosides (as monomers X4 and X5) into oligodeoxynucleotides was accomplished using the phosphoramidite approach on an automated DNA synthesizer. Irrespective of monomeric configuration, hybridization studies revealed that these 2'-spironucleotide monomers (X4 and X5) induce decreased duplex thermostabilities compared with the corresponding DNA:DNA and DNA:RNA duplexes. Molecular modelling indicated that steric constraints are a possible reason for the lowered binding affinities of the modified oligodeoxynucleotides towards complementary single-stranded DNA and single-stranded RNA complements.

Anti-HIV Agents↗

PubMed2002

Alpha-L-RNA (alpha-L-ribo configured RNA): synthesis and RNA-selective hybridization of alpha-L-RNA/alpha-L-LNA chimera.

Synthesis of the novel alpha-L-ribofuranosyl phosphoramidite derivative was accomplished via the alpha-L-ribofuranosyl thymine nucleoside. Amidite was used in automated syntheses of chimeric oligonucleotides composed of mixtures of the novel alpha-L-RNA nucleotide monomer ((alphaL)T, alpha-L-ribo configured RNA), and DNA, LNA (T(L), locked nucleic acid) or alpha-L-LNA ((alphaL)T(L), alpha-L-ribo configured locked nucleic acid) nucleotide monomers. For alpha-L-RNA/DNA and alpha-L-RNA/alpha-L-LNA chimeras, RNA-selective hybridization was obtained, for alpha-L-RNA/alpha-L-LNA chimera we found increased binding affinity compared to the corresponding DNA:RNA reference duplex. In addition, alpha-L-RNA/alpha-L-LNA chimera displayed significant stabilization towards 3'-exonucleolytic degradation. These results indicate that alpha-L-RNA/alpha-L-LNA chimeras deserve further evaluation as antisense molecules.

Nucleic Acid Conformation↗

PubMedDate not supplied

Synthesis of 2'-spiro ribo- and arabinonucleosides.

Four conformationally restricted bicyclic 2'-spiro nucleosides were synthesised and incorporated into oligonucleotides. These spiro nucleotides induced decreased duplex thermostabilities.

Arabinonucleosides↗