A library of neutral, hydrophobic reagents was synthesized for use as derivatizing agents in order to increase the ion abundance of N-linked glycans in electrospray ionization mass spectrometry (ESI MS). The glycans are derivatized via hydrazone formation and are shown to increase the ion abundance of a glycan standard more than 4-fold. Additionally, the data show that the systematic addition of hydrophobic surface area to the reagent increases the glycan ion abundance, a property that can be further exploited in the analysis of glycans. The results of this study will direct the future synthesis of hydrophobic reagents for glycan analysis using the correlation between hydrophobicity and theoretical non-polar surface area calculation to facilitate the development of an optimum tag for glycan derivatization. The compatibility and advantages of this method are demonstrated by cleaving and derivatizing N-linked glycans from human plasma proteins. The ESI-MS signal for the tagged glycans are shown to be significantly more abundant, and the detection of negatively charged sialylated glycans is enhanced.

A concise synthesis of (S)-macrostomine has been accomplished in five steps from natural nicotine in 19% overall yield via a pyridyne Diels-Alder cycloaddition reaction as the key step. A Kumada cross-coupling reaction on a 1-chloroisoquinoline intermediate provided the natural product.

Please cite this article as: Enamorado, M.F., Connelly, C.M., Deiters, A., Comins, D.L., A concise synthesis of the Lycopodium alkaloid cermizine D, Tetrahedron Letters (2015), doi: http://dx.ABSTRACT: A racemic and asymmetric synthesis of cermizine D (1) was accomplished in six steps from 4-methoxypyridine or 4-methoxy-3-TIPS-pyridine in 12% and 13% overall yield, respectively. A key step is a stereoselective 1,4-addition of a 2-((trimethylsilyl)methyl)pyridine-derived cuprate to a bicyclic 2,3-dihydro-4-pyridone. Racemic and (-)-cermizine D failed to exhibit cytotoxicity against four different cell lines.

The syntheses of seven novel amido nicotine derivatives 12-18 from (S)-nicotine are presented. (S)-Nicotine and (S)-6-chloronicotine derivatives were cross-coupled with the corresponding amides 6-10 at the C-4 position of the pyridine ring via copper(I)-mediated reactions. Derivatives 16-18 were also obtained via copper(II)-mediated reactions from (S)-nicotine containing a C-4 boronic acid pinacol ester group. The optimization of reaction conditions for both routes provided a useful method for preparing C-4 amide-containing nicotine analogs.