New Synthetic Approaches to Multifunctional Phenazinium Salt Derivatives

Two different approaches are offered for the synthesis under mild conditions of disubstituted phenazinium and benzo[a]phenazinium salts. Direct nucleophilic substitutions by primary and secondary amines in quaternary phenazinium salts containing an additional positive charge in the aliphatic part of the molecule were carried out. The substitution proceeds successively in positions 2 and 7, which allows selective introduction of different substituents into the heterocycle. Direct nucleophilic substitution in quaternary 2-N-alkyl-acetamidophenazinium and 5-alkoxy-benzo[a]phenazinium salts with different amines can also serve as a convenient method for the introduction of two different substituents

New Synthetic Approaches to Multifunctional Phenazinium Salt Derivatives

Abstract: Two different approaches are offered for the synthesis under mild conditions of disubstituted phenazinium and benzo[a]phenazinium salts. Direct nucleophilic substitutions by primary and secondary amines in quaternary phenazinium salts containing an additional positive charge in the aliphatic part of the molecule were carried out. The substitution proceeds successively in positions 2 and 7, which allows selective introduction of different substituents into the heterocycle. Direct nucleophilic substitution in quaternary 2-N-alkyl-acetamidophenazinium and 5-alkoxy-benzo[a]phenazinium salts with different amines can also serve as a convenient method for the introduction of two different substituents

Novel oligonucleotide analogues based on morpholino nucleoside subunits – Antisense technologies: New chemical possibilities

1721-1726 Even several decades after pioneer publications there is continued interest in the construction and synthesis of a variety of novel oligonucleotide analogues. The first oligonucleotide analogues which had a regular, predetermined structure containing nucleoside units joined with carbonate, carbamate, hydroxyacetate and hydroxyacetamide tethers have been developed in the 1970s. Further progress in oligonucleotide synthetic methods during the 1980s stimulated the development of a variety of oligonucleotide analogues containing modified carbohydrate and phosphate backbones. Particular attention has been given to the PNA (peptide nucleic acids), morpholino, and negatively charged PNA oligonucleotide analogues, which showed the most promise in a number of biological applications, such as diagnostics, nucleic acid analyses, and gene expression. The cost of parent compounds and oligonucleotide analogue synthesis is one of the most limiting factors to broad application. Studies that succeed in resolving this cost problem in the most effective way would be beneficial. Herein is presented a short review on oligonucleotide analogues that can be synthesized from inexpensive parent compounds — ribonucleosides — with or without the protection of heterocyclic bases, and with minimal protection of other reactive functions. </smarttagtype

Solid-phase-supported synthesis of morpholinoglycine oligonucleotide mimics

An efficient solid-phase-supported peptide synthesis (SPPS) of morpholinoglycine oligonucleotide (MorGly) mimics has been developed. The proposed strategy includes a novel specially designed labile linker group containing the oxalyl residue and the 2-aminomethylmorpholino nucleoside analogues as first subunits

Synthesis of nucleotide–amino acid conjugates designed for photo-CIDNP experiments by a phosphotriester approach

Conjugates of 2’-deoxyguanosine, L-tryptophan and benzophenone designed to study pathways of fast radical reactions by the photo Chemically Induced Dynamic Nuclear Polarization (photo-CIDNP) method were obtained by the phosphotriester block liquid phase synthesis. The phosphotriester approach to the oligonucleotide synthesis was shown to be a versatile and economic strategy for preparing the required amount of high quality samples of nucleotide–amino acid conjugates

Novel Convenient Approach to the Solid-Phase Synthesis of Oligonucleotide Conjugates

A novel and convenient approach for the solid-phase 5&prime;-functionalization of oligonucleotides is proposed in this article. The approach is based on the activation of free 5&prime;-hydroxyl of polymer support-bound protected oligonucleotides by N,N&prime;-disuccinimidyl carbonate followed by interaction with amino-containing ligands. Novel amino-containing derivatives of closo-dodecaborate, estrone, cholesterol, and &alpha;-tocopherol were specially prepared. A wide range of oligonucleotide conjugates bearing closo-dodecaborate, short peptide, pyrene, lipophilic residues (cholesterol, &alpha;-tocopherol, folate, estrone), aliphatic diamines, and propargylamine were synthesized and characterized to demonstrate the versatility of the approach. The developed method is suitable for the conjugate synthesis of oligonucleotides of different types (ribo-, deoxyribo-, 2&prime;-O-methylribo-, and others)

Multicomponent synthesis of artificial nucleases and their RNase and DNase activity

The synthesis of new, artificial ribonucleases containing two amino acid residues connected by an aliphatic linker has been developed. Target molecules were synthesized via a catalytic three-component Ugi reaction from aliphatic diisocyanides. Preliminary investigations proved unspecific nuclease activity of the new compounds towards single-stranded RNA and double-stranded circular DNA

Homocystamide Conjugates of Human Serum Albumin as a Platform to Prepare Bimodal Multidrug Delivery Systems for Boron Neutron Capture Therapy

Boron neutron capture therapy is a unique form of adjuvant cancer therapy for various malignancies including malignant gliomas. The conjugation of boron compounds and human serum albumin (HSA)—a carrier protein with a long plasma half-life—is expected to extend systemic circulation of the boron compounds and increase their accumulation in human glioma cells. We report on the synthesis of fluorophore-labeled homocystamide conjugates of human serum albumin and their use in thiol-‘click’ chemistry to prepare novel multimodal boronated albumin-based theranostic agents, which could be accumulated in tumor cells. The novelty of this work involves the development of the synthesis methodology of albumin conjugates for the imaging-guided boron neutron capture therapy combination. Herein, we suggest using thenoyltrifluoroacetone as a part of an anticancer theranostic construct: approximately 5.4 molecules of thenoyltrifluoroacetone were bound to each albumin. Along with its beneficial properties as a chemotherapeutic agent, thenoyltrifluoroacetone is a promising magnetic resonance imaging agent. The conjugation of bimodal HSA with undecahydro-closo-dodecaborate only slightly reduced human glioma cell line viability in the absence of irradiation (~30 μM of boronated albumin) but allowed for neutron capture and decreased tumor cell survival under epithermal neutron flux. The simultaneous presence of undecahydro-closo-dodecaborate and labeled amino acid residues (fluorophore dye and fluorine atoms) in the obtained HSA conjugate makes it a promising candidate for the combination imaging-guided boron neutron capture therapy