Gregory K. Pierens

Direct Visualization of Disulfide Bonds through Diselenide Proxies Using 77Se NMR Spectroscopy

Se-ing is believing: Many proteins are cross-braced by disulfide bonds that frequently play key roles in protein structure, folding, and function. Unfortunately, the methods available for assignment of disulfide-bond connectivities in proteins are technically difficult and prone to misinterpretation. Now disulfide bond connectivities in native proteins can be visualized directly using 77Se NMR spectroscopy.

Determination of Analyte Concentration using the Residual Solvent Resonance in 1H NMR Spectroscopy

An NMR protocol that uses the residual proton signal from DMSO -d(6) (i.e., DMSO -d(5)) to determine the concentration of an analyte in a NMR sample was developed. This technique provides an alternative method for determining the molar concentration of compounds in solution without prior knowledge of their molecular weight. The method is particularly useful when submilligram quantities of compound are to be analyzed and is applicable to a variety of different research areas such as compound management, and natural product, combinatorial, and medicinal chemistry.

1H and 13C NMR scaling factors for the calculation of chemical shifts in commonly used solvents using density functional theory.

Calculation of NMR chemical shifts and coupling constants using quantum mechanical calculations [density functional theory (DFT)], has become a very popular tool for the determination of conformation and the assignment of stereochemistry within a molecule. We present the scaling factors (linear regression parameters) from 10 DFT methods for 10 commonly used NMR solvents using the same set of reference compounds. The results were compared with the corresponding gas‐phase calculations to assess the inclusion of the polarizable continuum model for solvent effects.

Secondary metabolites of the sponge-derived fungus Acremonium persicinum.

This study reports the isolation and characterization of six new acremine metabolites, 5-chloroacremine A (4), 5-chloroacremine H (5), and acremines O (6), P (7), Q (8), and R (9), together with the known acremines A (1), F (2), and N (3) from the fungus Acremonium persicinum cultured from the marine sponge Anomoianthella rubra. The relative configuration of acremine F (2) was determined by analyses of proton coupling constant values and NOESY data, and the absolute configuration confirmed as (1S, 4S, 6R) by X-ray crystallographic analysis of the borate ester derivative 15. Acremines O, P, and R were each shown to be of 8R configuration by ¹H NMR analyses of MPA esters. The relative configurations suggested for acremines P and Q were each deduced by molecular modeling together with NOESY and coupling constant data. The ³J(H-C) values in acremine P were measured using the pulse sequence EXSIDE, and the observed ³J(H8-C4) of 5.4 Hz and small ³J(H-C) values (<1.5 Hz) from H-8 to C-10 and C-11 were fully consistent with stereoisomer 7a. For acremine Q, NOESY data combined with molecular modeling established the preferred diastereomer 8a.

Selection of Multiple-Quantum Spectra of Molecules in Liquid-Crystalline Solution Using Pulsed Magnetic-Field Gradients

Herchel Smith Laboratory for Medicinal Chemistry, University of Cambridge School of Clinical Medicine, lfniversity Forvie Site, Robinson Way, Cambridge CB2 2PZ, United Kingdom; *Department of Chemistry and Biochemistry, Concordia University, 1455 de Maisonneuve Boulevard, WY. Montreal, Quebec, Canada H3G IMS; and t Department qf Organic chemistry, University qf

Rearranged Diterpenes and Norditerpenes from Three Australian Goniobranchus Mollusks

vdney, 2006 New South Wales, Aastralia

New Cytotoxic Norditerpenes from the Australian Nudibranchs Goniobranchus Splendidus and Goniobranchus Daphne

Three new norditerpenes (1, 6, and 7) and four diterpenes (2-5) with extensively rearranged carbon skeletons have been characterized from Australian nudibranchs. The relative configuration of the cyclopropyl-containing verrielactone (1) from Goniobranchus verrieri was suggested by spectroscopic analysis at 500 MHz informed by a combination of molecular modeling and DFT calculations. The nudibranchs G. splendidus and G. cf. splendidus provided 2-7, for which the structures and stereochemistry were deduced by 2D NMR studies at either 500 or 700 MHz. Each of the seven terpenoids exhibited a carbon skeleton modified from one of the tetrahydroaplysulphurin, spongionellin, or gracilane series of terpenes. A biosynthetic pathway to terpenes 1-7 from spongialactone is proposed.

Psammaplin Metabolites New and Old: An NMR Study Involving Chiral Sulfur Chemistry

This study reports the isolation and characterisation of six new metabolites with ‘gracilin’-type carbon skeletons and of aplytandiene-3 from the Australian nudibranch Goniobranchus splendidus. The structure of gracilin G is revised, and the C-6 configuration deduced by comparison of calculated 3JC/H values with values measured using the EXSIDE pulse sequence. A lactone isolated from Goniobranchus daphne contains a rearranged spongionellin-type skeleton. Screening of selected metabolites revealed significant cytotoxicity against a HeLa S3 cell line by five of the new terpenes.

Isolation of two phenylethanoid glycosides from Eremophila gilesii

The new metabolite psammaplin N (8) that contains a sulfoxide moiety has been isolated together with psammaplins A (1), I (4a), and J (2) from a specimen of the marine sponge Aplysinella rhax (order Verongida family Aplysinidae) collected in South East Queensland. An NMR study on psammaplin J reveals its facile conversion to psammaplins A and I when exposed to methanol.

Multiple-Quantum Nmr-Spectroscopy of Molecules Aligned in Liquid-Crystalline Solvents

The leaves of Eremophila gilesii have been used traditionally to treat colds, headaches, sores, and chest pains. Our previous screening of Australian native plants showed that the methanol extract of the aerial parts of E. gilesii demonstrated notable inhibition of ADP-induced human platelet aggregation and serotonin release. Subsequent fractionation on the methanol extract led to the isolation of two phenylethanoid glycosides, verbascoside (1) and poliumoside (2). This is the first study reporting the presence of phenylethanoid glycosides in E. gilesii.