Andrew Edmund Taggi

NMR-spectroscopic screening of spider venom reveals sulfated nucleosides as major components for the brown recluse and related species

Extensive chemical analyses of spider venoms from many species have revealed complex mixtures of biologically active compounds, of which several have provided important leads for drug development. We have recently shown that NMR spectroscopy can be used advantageously for a direct structural characterization of the small-molecule content of such complex mixtures. Here, we report the application of this strategy to a larger-scale analysis of a collection of spider venoms representing >70 species, which, in combination with mass spectrometric analyses, allowed the identification of a wide range of known, and several previously undescribed, small molecules. These include polyamines, common neurotransmitters, and amino acid derivatives as well as two additional members of a recently discovered family of natural products, the sulfated nucleosides. In the case of the well studied brown recluse spider, Loxosceles reclusa, sulfated guanosine derivatives were found to comprise the major small-molecule components of the venom.

Sequential Column Asymmetric Catalysis

Since the introduction of catalysts and reagents on solid-support, researchers have developed new reaction systems to take advantage of their insoluble nature by designing multistep reaction sequences, high-throughput purification techniques, and combinatorial synthesis methods. The continuous flow system is one of these advancements and represents the foundation of a new technique termed sequential column asymmetric catalysis (CAC). In this strategy, reagents and catalysts are attached to a solid-phase support and loaded onto sequentially-linked columns. The substrates are present in the liquid phase that flows through the column. As a substrate encounters each successive column, it grows in complexity. Consequently, one can imagine a number of flow systems that consist of columns attached in series and/or in parallel that synthesize a fairly complex molecule. Herein, we discuss the development of the sequential CAC technique, beginning with the most relevant antecedents.

Molecular mechanics calculations as predictors of enantioselectivity for chiral nucleophile catalyzed reactions

We present molecular mechanics (MM) calculations as models of activated complexes for the β-lactam forming [2+2] cycloaddition between imino ester 4 and the zwitterionic intermediates derived from ketenes and various chiral nucleophilic catalysts. Our method employs the use of Monte Carlo conformational searches utilizing the MMFF force field contained within the Macromodel program. These models accurately predict the sense of stereochemical induction observed experimentally. Also, the predicted energetic differences for minima leading to (R) or (S)-derived ketene facial selectivity correlate in a general sense with the magnitude of the enantioselectivity. This work establishes that our approach represents a viable method for the design of new nucleophilic catalysts a priori using MM calculations.

Tubulin modulating antifungal and antiproliferative pyrazinone derivatives

A novel class of synthetic tubulin polymerization disruptors, based on a substituted pyrazin-2-one core, has been discovered. These molecules have proven to be potent broad spectrum fungicides, with activity on agriculturally important ascomycete and basidiomycete pathogens. They have also been found to be particularly potent against human rhabdomyosarcoma cells. Using an efficient synthetic route, the agricultural and medicinal activity was explored.