Synthesis of dopamine and serotonin derivatives for immobilization on a solid support

The two important neurotransmitters dopamine and serotonin are synthesized with short PEG tethers and immobilized on a magnetic solid support. The tether is attached to the aromatic moiety of the neurotransmitters to conserve their original functional groups. This approach causes minimal alteration of the original structure with the aim of optimizing the immobilized neurotransmitters for aptamer selection by SELEX. For the dopamine derivative, the tether is attached to the aromatic core of a dopamine precursor by the Sonogashira reaction. For serotonin, a link to the indole core is introduced by a Claisen rearrangement from the allylated phenol moiety of serotonin. The tethers are azide-functionalized, which enables coupling to alkyne-modified magnetic beads. The coupling to the magnetic beads is quantified by UV spectroscopy using Fmoc-monitoring of the immobilized dopamine and serotonin derivatives.     

Simple strategy for the immobilization of dirhodium tetraprolinate catalysts using a pyridine-linked solid support

Dirhodium tetracarboxylates are readily immobilized on agitation in the presence of highly cross-linked polystyrene resins with a pyridine attachment. A systematic study demonstrates that the polymer backbone, the linker, the terminal pyridine group, and the catalyst structure all contribute to the efficiency of dirhodium catalyst immobilization. The immobilization is considered to be due to the combination of ligand coordination and encapsulation. The dirhodium tetraprolinate catalysts, Rh2(S-DOSP)4 (1a), Rh2(S-TBSP)4 (1b), and Rh2(S-biTISP)2 (2), are all efficiently immobilized. The resulting heterogeneous complexes are very effective catalysts for asymmetric cyclopropanation between methyl phenyldiazoacetate and styrene, and under optimized conditions they can be recycled five times with virtually no loss in enantioselectivity. The three-phase test studies indicated that a very slow reaction occurs when both the catalyst and the diazo compound were immobilized, but the slow rate precluded the likelihood that the cyclopropanation was predominately occurring by a release-and-capture mechanism.     

Imidazole synthesis on a solid support

Imidazole synthesis has been demonstrated using polymer supported O-carboxamido -5-aminoimidazole and hypoxanthine.     

Facile method for the synthesis of triazole- and tetrazole-containing peptoids on a solid support

The late-stage functionalization of a biomimetic foldamer such as a peptoid is a useful tool to achieve structural diversity. Herein, a facile method for the synthesis of triazole- or tetrazole-containing peptoids using post-synthetic modifications has been reported. On a resin-bound peptoid with a chloroalkyl side chain(s), substitution with nucleophiles (azide or cyanide) and the subsequent [3?+?2]-cycloaddition reaction were optimized. Peptoids with azide, triazole, and tetrazole functional groups could be readily synthesized and could potentially be utilized further for orthogonal bioconjugation or metal recognition.     

A new procedure for the synthesis of peptide-derived Amadori products on a solid support

A new and straightforward solid-phase synthesis of a series of site-specific Amadori-modified peptides is described. The method involves reductive alkylation of the ε-amino groups of lysine with 2,3:4,5-di-O-isopropylidene-β-d-arabino-hexos-2-ulo-2,6-pyranose in the presence of sodium cyanoborohydride on a solid support.     

A novel solid support for the synthesis of 3-aminoalkylated oligonucleotides

A novel improved controlled pore glass (CPG) support based on the 2-(hydroxymethyl)-6-nitrobenzoyl (HMNB) protecting group was developed for the synthesis of 3^′-aminoalkylated oligonucleotides. The release of oligonucleotides with free 3^′-amino groups from the support is complete within 2 h at 55 °C in concentrated ammonia.     

Protease-catalyzed peptide synthesis on solid support

The direct enzymatic synthesis of peptides from amino acids is widely used as a useful alternative to chemical synthesis. However, good yields of such enzyme-catalyzed reactions require altered reaction conditions to overcome the bias for hydrolysis in aqueous medium. We argue that the synthesis/hydrolysis equilibrium can be shifted toward synthesis in aqueous medium by immobilizing the amine on solid support. In this report, we show the first examples of solid-phase peptide synthesis catalyzed by a protease in bulk aqueous buffer.     

Total synthesis of laulimalide: assembly of the fragments and completion of the synthesis of the natural product and a potent analogue

Herein, we present a full account of our efforts to couple the northern and the southern building blocks, the synthesis of which were described in the preceding paper, along with the modifications required to ultimately lead to a successful synthesis of laulimalide. Key highlights include an exceptionally efficient and atom-economical intramolecular ruthenium-catalyzed alkene-alkyne coupling to build the macrocycle, followed by a highly stereoselective 1,3-allylic isomerization promoted by a rhenium complex. Interestingly, the designed synthetic route also allowed us to prepare an analogue of the natural product that possesses significant cytotoxic activity. We also report a second generation route that provides a more concise synthesis of the natural product.     

2-Bromoethyl glycosides for synthesis of glycoconjugates on solid support

2-Bromoethyl glycosides can easily and in high yields be transformed into sulfones by treatment with a suitable thiol followed by oxidation with mCPBA. The observation that the so formed sulfones were cleaved by treatment with NaOMe/MeOH was used to design a new safety catch linker for synthesis of glycoconjugates on solid support.     

Efficient synthesis of antisense phosphorothioate oligonucleotides using a universal solid support

It is demonstrated that solid support containing a novel universal linker could be efficiently used to synthesize both phosphorothioate oligodeoxyribonucleotides and second-generation 2′-O-methoxyethyloligoribonucleotides with high yield and quality as judged by ion-pair-liquid chromatography-electrospray mass spectroscopy, ³¹P NMR and reversed phase HPLC. Analysis of oligonucleotides shows quality being superior to that produced with standard succinyl-linker solid supports, without contamination of materials resulting from linker or support backbone decomposition.     

A conformationally preorganized universal solid support for efficient oligonucleotide synthesis

A novel, conformationally preorganized nonnucleosidic universal solid support for oligonucleotide synthesis was developed. The solid support featured two chemically equivalent hydroxy groups locked in syn-periplanar orientation and orthogonally protected with 4,4'-dimethoxytrityl and acetyl groups. The solid support was extensively tested in the preparation of oligonucleotides and their phosphorothioate analogues containing 2'-deoxy, 2'-O-methyl, and 2'-O-methoxyethylnucleoside residues at the 3'-terminus. Upon completion of oligonucleotide chain assembly, the support-bound oligonucleotide material was treated with concentrated ammonium hydroxide, which removed the O-acetyl protection. The deprotected hydroxy group then effected the transesterification of a phosphate linkage between the solid support and the 3'-terminal nucleoside residue to result in a facile release of the oligonucleotide to solution. The kinetics of the release process was studied in a continuous flow of concentrated aqueous ammonium hydroxide at a temperature of 300.15 K. Optimal conditions for the release of oligonucleotides depending on the chemistry of the backbone and 3'-terminal nucleoside residue were formulated.     

Oriented immobilization of chymotrypsin by use of suitable antibodies coupled to a nonporous solid support.

In order to eliminate the kinetic limitation of chymotryptic hydrolysis of proteins due to diffusion, nonporous hydroxyalkyl methacrylate solid support was developed and used for oriented immobilization of chymotrypsin by means of suitable polyclonal antibodies. Nonporous microspheres were prepared by dispersion copolymerization of 2-hydroxyethyl methacrylate and ethylene dimethacrylate in an alcohol-toluene mixture stabilized with cellulose acetate butyrate. The resulting particles were 1.2 microm in diameter and possessed narrow size distribution. After modification with adipic acid dihydrazide they contained 2 micromol of reactive groups available for coupling of anti-chymotrypsin antibodies. Prepared immunosorbent adsorbed 166.7 microg of chymotrypsin per 1 g of dry carrier. Immobilized chymotrypsin retained practically 100% of its native proteolytic activity. Kinetic parameters of catalysis by chymotrypsin immobilized via this way were improved due to the good steric accessibility of the enzyme active site for high-molecular-mass substrates, when digestion of proteins in batch experiments was used.     

Enzymatic synthesis of beta-mannosyl phosphates on solid support

Synthetic bifunctional analogues 4a, b and 14 of dolichol phosphate 1 were attached to solid support and were shown to be substrates for Dol-P-Man synthase.     

Silica gel as solid support in the synthesis of oligoribonucleotides

A method is described for the synthesis of ribonucleotides using silica gel as a polymer support. Yields were > 85% at each step in the synthesis of a hexanucleotide containing all four common ribonucleosides.     

Optimization of glutaraldehyde activation of a support for enzyme immobilization

The influence of several parameters (support porosity, glutaraldehyde concentration, time of action, pH) on the activation reaction of an amine porous silica (Spherosil) with glutaraldehyde has been studied. Glutaraldehyde binding onto the support was followed by measuring the carbon content of the activated silica.We established comparisons between the quantity of glutaraldehyde retained on the support after activation and the capacity of the activated silica to bind trypsin. We have defined the optimal conditions for Spherosil activation and prepared derivatives with high enzymatic activity.Our results are in agreement with a reaction mechanism with glutaraldehyde in a polymeric form resulting from aldol condensation, rather than in a monomeric form.