https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

A review of sterol markers for marine and terrigenous organic matter

: The unpolarized absorption and circular dichroism spectra of the fundamental vibrational transitions of the chiral molecule, 4-methyl-2-oxetanone, are calculated ab initio. Harmonic force fields are obtained using Density Functional Theory (DFT), MP2, and SCF methodologies and a 5S4P2D/3S2P (TZ2P) basis set. DFT calculations use the Local Spin Density Approximation (LSDA), BLYP, and Becke3LYP (B3LYP) density functionals. Mid-IR spectra predicted using LSDA, BLYP, and B3LYP force fields are of significantly different quality, the B3LYP force field yielding spectra in clearly superior, and overall excellent, agreement with experiment. The MP2 force field yields spectra in slightly worse agreement with experiment than the B3LYP force field. The SCF force field yields spectra in poor agreement with experiment.The basis set dependence of B3LYP force fields is also explored: the 6-31G* and TZ2P basis sets give very similar results while the 3-21G basis set yields spectra in substantially worse agreements with experiment. jg

Ab initio calculation of vibrational absorption and circular dichroism spectra using density functional force fields

NMR spectroscopy in the structural elucidation of oligosaccharides and glycosides.

Natural products and their structural analogues have historically made a major contribution to pharmacotherapy, especially for cancer and infectious diseases. Nevertheless, natural products also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization, which contributed to a decline in their pursuit by the pharmaceutical industry from the 1990s onwards. In recent years, several technological and scientific developments — including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances — are addressing such challenges and opening up new opportunities. Consequently, interest in natural products as drug leads is being revitalized, particularly for tackling antimicrobial resistance. Here, we summarize recent technological developments that are enabling natural product-based drug discovery, highlight selected applications and discuss key opportunities. Natural products have historically made a major contribution to pharmacotherapy, but also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization. This Review discusses recent technological developments — including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances — that are enabling a revitalization of natural product-based drug discovery.

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Natural products in drug discovery: advances and opportunities.

Despite the inherently low sensitivity of 15N NMR because of its low gyromagnetic ratio (γN) and its relatively low natural abundance (0.37%), this important nuclide still has useful potential as a structural probe even at natural abundance. Inverse-detected NMR methods coupled with major advances in NMR probe designs have made it possible to acquire long-range 1H−15N heteronuclear shift correlation data on samples as small as a micromole overnight. Chemical shift referencing schemes for 15N and the range of 15N shifts are discussed, followed by a discussion of the currently available pulse sequences, pulse calibration, parametrization and processing of long-range 1H−15N data, and the implications of probe selection. These topics are followed by a review of the applications contained in the literature that have utilized 1H−15N heteronuclear shift correlation experiments at natural abundance, with emphasis placed on the observed long-range coupling pathways.

Long-Range 1H−15N Heteronuclear Shift Correlation at Natural Abundance

Two new indoloquinoline alkaloids from cryptolepis sanguinolenta: Cryptosanguinolentine and cryptotackieine

Inverse-detected two-dimensional nmr methods : applications in natural products chemistry

HMBC is one of the most often used and vital NMR experiments for the structure elucidation of organic and inorganic molecules. We have developed a new, high sensitivity NMR pulse sequence that overcomes the typical 2,3JCH limitation of HMBC by extending the visualization of long-range correlation data to 4-, 5-, and even 6-bond long-range nJCH heteronuclear couplings. This technique should prove to be an effective experiment to complement HMBC for probing the structure of proton-deficient molecules. The LR-HSQMBC NMR experiment can, in effect, extend the range of HMBC to provide data similar to that afforded by 1,n-ADEQUATE even in sample-limited situations. This is accomplished by optimizing responses for very small nJCH coupings as opposed to relying on the markedly less sensitive detection of long-range coupled 13C–13C homonuclear pairs at natural abundance. DFT calculations were employed to determine whether the very long-range correlations observed for cervinomycin A2 were reasonable on the basis of ...

LR-HSQMBC: A Sensitive NMR Technique To Probe Very Long-Range Heteronuclear Coupling Pathways

A further refinement of the recently reported IMPEACH-MBC long-range heteronuclear shift correlation experiment is described. The new experiment, CIGAR-HMBC (constant time inverse-detected gradient accordion rescaled long-range heteronuclear multiple bond correlation), modifies the constant time variable delay of the IMPEACH-MBC experiment to allow user-determined scaling of F1 modulation. The refinement offered in the CIGAR-HMBC experiment allows the investigator to reintroduce whatever degree of F1 modulation is desired to authenticate weak long-range responses. Results obtained with the CIGAR-HMBC experiment using a range of values for Jscale are compared with results obtained with identically optimized ACCORD-HMBC and IMPEACH-MBC experiments. Copyright © 2000 John Wiley & Sons, Ltd.

Gary E. Martin

Papers

Long-Range 1H−15N Heteronuclear Shift Correlation at Natural Abundance

Two new indoloquinoline alkaloids from cryptolepis sanguinolenta: Cryptosanguinolentine and cryptotackieine

Inverse-detected two-dimensional nmr methods : applications in natural products chemistry

LR-HSQMBC: A Sensitive NMR Technique To Probe Very Long-Range Heteronuclear Coupling Pathways

Constant time inverse-detection gradient accordion rescaled heteronuclear multiple bond correlation spectroscopy: CIGAR-HMBC