Laszlo Varady

Fimbriated stationary phases for proteins

This paper describes synthetic procedures for preparing fimbriated stationary phases on poly(styrene-divinylbenzene) (PS-DVB) packing materials. The synthesis consists of a five-step procedure in which the order in which the steps are carried out may be varied. These steps are (i) polymerization of monomers to form an amphiphilic copolymer or oligomer, (ii) adsorption of either monomers, or polymer onto the PS-DVB surface, (iii) solvent induction of functional group orientation at the PS-DVB-polymer interface and polymer-water interface, (iv) a cross-linking reaction that forms a hydrophilic surface layer, and (v) derivatization of the surface layer with stationary phase.

Thermodynamic model for electrostatic-interaction chromatography of proteins

A thermodynamic model derived by Record et al. [M. T. Record, Jr., Biopolymers, 14 (1975) 2137 and M. T. Record, Jr., C. F. Anderson and T. M. Lohman, Q. Rev. Biophys., 11 (1978) 103] from Wymans linkage theory [J. Wyman, Adv. Protein Chem., 19 (1964) 223] using Mannings condensation model [J. Manning, J. Chem. Phys., 51 (1969) 924] was extended to electrostatic interaction chromatography. Mixed, electrostatic and hydrophobic interactions of a model protein, ovalbumin were characterized by ion and water release.

Alternative base matrices for solid phase quenching reagents

Abstract In this paper we describe the use of macroporous, highly cross-linked poly(styrene-divinylbenzene) as a base matrix for solid phase scavengers. We demonstrate that this matrix is superior to the more traditional Merrifield resins when non-swelling solvents like acetonitrile are used. A small library of sulfonamides is generated in high purity as an example.

Synthesis of a novel, recyclable, solid-phase acylating reagent.

In this paper, we describe the synthesis of N-(6-cyano-1,3-dimethyl-2,4-dioxo-5-substituted-1,3-dihydropyridino[2,3-d] pyrimidin-7-yl)imides 1. We will show the synthesis of 1 using both conventional heating and microwave techniques. In addition, the imide was attached to polystyrene and this immobilized imide was equally as effective at acylating various primary and secondary amines as its solution-phase counterpart.

A concise, total synthesis and antibacterial evaluation of 2-hydroxy-1-(1H-indol-3-yl)-4-methylpentan-3-one

Treatment of racemic 2-hydroxy-3-(1H-indol-3yl)propionic acid methyl ester (5) with isopropyl magnesium chloride provided the title compound 1 and its isomer, 3-hydroxy-1-(indol-3-yl)-4-methylpentan-2-one (9). Both enantiomers (>96% ee) of each component were obtained via semi-preparative chiral supercritical fluid chromatography (SFC). In contrast to previous reports, these compounds, as well as their acetate derivatives, were not active or very weakly active against 16 bacterial strains, including Escherichia coli, Bacillus subtilis and Staphylococcus aureus.

Fast and quantitative high-performance liquid chromatography method for the determination of 9-fluorenylmethoxycarbonyl release from solid-phase synthesis resins

Base catalyzed cleavage of 9-fluorenylmethoxycarbonyl (FMOC) group and subsequent analysis by UV spectrophotometry is a commonly used technique for measuring the loading of functional groups on solid supports. Recent works suggest that using 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU) instead of piperidine makes it possible to use gas chromatography for quantitation, but due to the long deprotection time used, the method is not high-throughput. We observed that the dibenzofulvene released after DBU deprotection could be measured by reversed-phase (RP) HPLC. We have optimized the concentration of DBU as well as the time of the deprotection and coupled with a fast RP-HPLC separation results in a highly reproducible, high-throughput method. The measured loading correspond well with the manufacturers data on several commercial resins. Using this method we have quantitated the amine loading on several polystyrene resins and we have found that the total amount of functional group can be more than twice the amount of the available ones. We concluded that the differences were the function of the resin loading as well as the level of crosslinking.

Synthesis of 4-pentenoic and 5-hexenoic acids on polystyrene resin and their use as cleavable linkers

Direct synthesis of 4-pentenoic and 5-hexenoic acid derivatives on polystyrene resin was achieved and their use as cleavable linkers in solid phase organic synthesis has been demonstrated.

2-(3-Aminopropyl)-4-pentenoic acid as a bio-compatible/cleavable linker for solid-phase organic synthesis

Abstract 2-(3-Aminopropyl)-4-pentenoic acid lithium salt ( 1 ) was prepared and used as a bio-compatible, cleavable linker in solid-phase organic synthesis. The products were released from solid support through cycloelimination.