Transition Metal Derivatives of Peptide Nucleic Acid (PNA) OligomersSynthesis, Characterization, and DNA Binding

This work describes the first automated solid-phase synthesis of metal derivatives of peptide nucleic acid (PNA) oligomers and their interaction with DNA and PNA. PNA constitutes a relatively young and very promising class of DNA analogues with excellent DNA and RNA binding properties. However, PNA lacks a suitable handle that would permit its sensitive detection on its own as well as when hybridized with complementary oligonucleotides. Metal complexes, on the other hand, offer high potential as markers for biomolecules. In this paper, we describe the synthesis of PNA heptamers (tggatcg-gly, where gly is a C-terminal glycine carboxylic acid amide) with two covalently attached metal complexes at the PNA N-terminus, namely a ferrocene carboxylic acid derivative and a tris(bipyridine)ruthenium(II) derivative. We show how all synthesis steps may be carried out with high yield on a DNA synthesizer, including attachment of the metal complexes. The conjugates were characterized by HPLC (>90% purity) and ESI-MS. Binding studies of the purified Ru-PNA heptamer to complementary DNA and PNA and comparison to the isosequential metal-free acetyl PNA heptamer proves that the attached metal complex has an influence on the stability (UV-Tm) and structure (CD spectroscopy) of the conjugates, possibly by disruption of the nearby A:T base pair

Binding of Daunorubicin to β-d-Glucosylated DNA Found in Protozoa <i>Tryponosoma brucei </i>Studied by X-ray Crystallography

Binding of Daunorubicin to β-d-Glucosylated DNA Found in Protozoa Tryponosoma brucei Studied by X-ray Crystallograph

Effective, High-Yielding, and Stereospecific Total Synthesis of d-<i>e</i><i>rythro</i>-(2<i>R</i>,3<i>S</i>)-Sphingosine from d-<i>r</i><i>ibo</i>-(2<i>S</i>,3<i>S</i>,4<i>R</i>)-Phytosphingosine

The synthesis of naturally occurring d-erythro-(2R,3S,4E)-sphingosine from commercially available d-ribo-(2S,3S,4R)-phytosphingosine is described. The key step in the reaction sequence comprises TMSI/DBN promoted regio- and stereoselective oxirane opening of intermediate 2-phenyl-4-(S)-[(1S,2S)-1,2-epoxyhexadecyl]-1,3-oxazoline followed by the in situ trans-elimination of 2-phenyl-4-(S)-[(1S,2R)-1,2-dideoxy-2-iodo-1-trimethylsilyloxyhexadecyl]-1,3-oxazoline

Stereoselective Transformations on d-Glucose-Derived Eight-Membered Ring Carbocycles

The cyclooctenol derivative 1 can be transformed into the nine-membered ring lactone 3, as well as the amino-containing carbocycles 4 and 5. The corresponding ketone 2 gives access to the conformationally locked azasugar 6

The Use of a Mannitol-Derived Fused Oxacycle as a Combinatorial Scaffold

An efficient and high-yielding solid-phase synthesis of a small library of compounds containing a cis-fused pyranofuran structural motive is descibed. With use of the cheap and readily available d-(+)-mannitol, a highly functionalized sugar template was synthesized and immobilized on a solid support via an olefinic linker. Modification of this two-point molecular scaffold and subsequent ring-closing metathesis/cleavage gave access to a series of functionalized conformationally constrained fused oxacycles

The Use of a Mannitol-Derived Fused Oxacycle as a Combinatorial Scaffold

An efficient and high-yielding solid-phase synthesis of a small library of compounds containing a cis-fused pyranofuran structural motive is descibed. With use of the cheap and readily available d-(+)-mannitol, a highly functionalized sugar template was synthesized and immobilized on a solid support via an olefinic linker. Modification of this two-point molecular scaffold and subsequent ring-closing metathesis/cleavage gave access to a series of functionalized conformationally constrained fused oxacycles

Sequential One-Pot Glycosylations Using 1-Hydroxyl and 1-Thiodonors

A novel sequential glycosylation procedure is described that combines the use of 1-hydroxyl and thiodonors. The Ph2SO/Tf2O-mediated dehydrative condensation of 1-hydroxyl donors with thioglycosides affords in good yield the thiodisaccharides, which in turn can be activated by the same activator system to furnish trisaccharides. The α-Gal epitope and a hyaluronan trisaccharide were efficiently assembled in a one-pot procedure

A Short Route toward Chiral, Polyhydroxylated Indolizidines and Quinolizidines

In this paper, a rapid route toward functionalized bicyclic alkaloids is presented. In only three steps, an easily accessible carbohydrate derivative was converted into iodomethyl indolizidine 13, which can equilibrate to the corresponding iodoquinolizidine 15. We provide strong evidence that this equilibration proceeds via an aziridinium ion intermediate. Furthermore, nucleophilic substitution of the iodomethyl indolizidine as well as the aziridinium intermediate gives access to highly functionalized indolizidine and quinolizidine alkaloids

Radical Cyclization of Sugar-Derived β-(Alkynyloxy)acrylates: Synthesis of Novel Fused Ethers

Tributyltin radical mediated cyclization of carbohydrate-derived β-(alkynyloxy)acrylates leading to highly functionalized cis- and trans-fused bicyclic ethers of various ring sizes is described. The efficacy of the radical cyclization is nicely illustrated in the iterative construction of a trans-fused tricyclic tetrahydropyran

A Modular Strategy Toward the Synthesis of Heparin-like Oligosaccharides Using Monomeric Building Blocks in a Sequential Glycosylation Strategy

A novel flexible assembly strategy is described for the modular synthesis of heparin and heparan sulfates. The reported strategy uses monomeric building bocks to construct the oligosaccharide chain to attain a maximum degree of flexibility. In the assembly, 1-hydroxyl glucosazido- and 1-thio uronic acid donors are combined in a sequential glycosylation protocol using sulfonium triflate activator systems. The key 1-thio uronic acids were obtained in an efficient manner from diacetone glucose employing a chemo- and regioselective oxidation of partially protected glucose and idose thioglycosides