William Lee Seibel

The synthesis of aza-β-lactams via tandem Petasis-Ugi multi-component condensation and 1,3-diisopropylcarbodiimide (DIC) condensation reaction

Abstract The synthetic utility of a tandem Petasis–Ugi multi-component condensation and 1,3-diisopropylcarbodiimide condensation reactions have been employed to efficiently prepare two to four-dimensional libraries of aza-β-lactams.

Applications of solid supported azide anion: a one-pot, two-step preparation of functionalized 1,2,3-triazoles

Functionalized 1,2,3-triazoles were prepared in a one-pot, two-step synthesis from alkyl halides and alkynes using a polymer supported azide. Two different base resins were examined. The chemistry is suitable for the preparation of combinatorial libraries.

Novel Petasis boronic acid–Mannich reactions with tertiary aromatic amines

Tertiary aromatic amines can serve as amine substrates for the Petasis boronic acid–Mannich reaction, providing a practical synthetic route for the CC bond formation of α-(4-N,N-dialkylamino-2-alkyloxyphenyl)carboxylic acids. The scope and limitations of this method have been examined.

A novel method for the efficient synthesis of 2-arylamino-2-imidazolines

Abstract A novel method for the efficient synthesis of 2-arylamino-2-imidazolines is described.

Highly sensitive high-performance liquid chromatographic-tandem mass spectrometric method for the analysis of dextromethorphan in human plasma

A stable-isotope-dilution HPLC-tandem mass spectrometry-based method was developed for the determination of dextromethorphan in human plasma. Plasma samples were prepared for analysis by solid-phase extraction on octadecylsilane extraction cartridges. Dextromethorphan and the deuterium-labeled dextromethorphan internal standard were chromatographed on a short reversed-phase column and detected by a selected-reaction-monitoring scheme. Linear standard curves were obtained over three orders of magnitude and the limit of quantitation for dextromethorphan was 50 pg/ml, using a 1-ml plasma sample. The combination of HPLC and electrospray tandem mass spectrometry resulted in a rapid, selective and sensitive method for the analysis of dextromethorphan in plasma. The method was applied for the evaluation of the pharmacokinetic profile of dextromethorphan in human volunteers following peroral administration.

Serendipitous discovery of novel bacterial methionine aminopeptidase inhibitors

In this article we describe the application of structural biology methods to the discovery of novel potent inhibitors of methionine aminopeptidases. These enzymes are employed by the cells to cleave the N‐terminal methionine from nascent peptides and proteins. As this is one of the critical steps in protein maturation, it is very likely that inhibitors of these enzymes may prove useful as novel antibacterial agents. Involvement of crystallography at the very early stages of the inhibitor design process resulted in serendipitous discovery of a new inhibitor class, the pyrazole‐diamines. Atomic‐resolution structures of several inhibitors bound to the enzyme illuminate a new mode of inhibitor binding. Proteins 2007.

A simple method for the preparation and selective functionalization of 4,5-diaminopyrazoles

Abstract A simple procedure for the synthesis and further functionalization of 4,5-diaminopyrazoles using mild conditions is reported herein. The desired products were obtained in good yield, and the structures have been confirmed by X-ray crystallography.

Positional isomerization of quinine and quinidine via rhodium on alumina catalysis: practical one-step synthesis of Δ3,10-isoquinine and Δ3,10-isoquinidine

Abstract The synthesis of Δ 3,10 -isoquinine ( 5 Z , 5 E ) and Δ 3,10 -isoquinidine ( 6 Z , 6 E ) was achieved in one-step through positional isomerization of the terminal alkene in the parent cinchona alkaloids using catalytic amounts of 5% Rh/Al 2 O 3 and excess hydrochloric acid in refluxing 50% aqueous EtOH. The products were obtained in good yields as a mixture of E and Z geometric isomers and fully characterized using spectroscopic methods.