Metal-catalysed C–H bond functionalisation has had a significant impact on how chemists make molecules. Translating the methodological developments to their use in the assembly of complex natural products is an important challenge for the continued advancement of chemical synthesis. In this tutorial review, we describe selected recent examples of how the metal-catalysed C–H bond functionalisation has been able to positively affect the synthesis of natural products.

Recent developments in natural product synthesis using metal-catalysed C–H bond functionalisation

Spectroscopy is the study of matter interacting with electromagnetic radiation (e.g., light). The electromagnetic spectrum in Figure 1 illustrates the many different types of electromagnetic radiation, including gamma rays (γ-rays), X-rays, ultraviolet (UV) radiation, visible light, infrared (IR) radiation, microwaves, and radio waves. The frequency (ν) and wavelength (λ) ranges associated with each form of radiant energy are also indicated in Figure 1.

Introduction to Spectroscopy

In this critical review the applications of gold catalysed reactions in total synthesis during the years since our last article are reviewed. At the end of this article a literature analysis is conducted to evaluate the progress in this field.

Gold catalysis in total synthesis – recent achievements

GIAO NMR shift calculation has been applied to the challenging task of reliably assigning stereochemistry with quantifiable confidence when only one set of experimental data are available. We have compared several approaches for assigning a probability to each candidate structure and have tested the ability of these methods to distinguish up to 64 possible diastereoisomers of 117 different molecules, using NMR shifts obtained in rapid and computationally inexpensive single-point calculations on molecular mechanics geometries without time-consuming ab initio geometry optimization. We show that a probability analysis based on the errors in each 13C or 1H shift is significantly more successful at making correct assignments with high confidence than are probabilities based on the correlation coefficient and mean absolute error parameters. Our new probability measure, which we have termed DP4, complements the probabilities obtained from our previously developed CP3 parameter, which applies to the case of assig...

Assigning Stereochemistry to Single Diastereoisomers by GIAO NMR Calculation: The DP4 Probability

The Lycopodium alkaloids

Two new isocoumarin glucosides, haworforbins A (1) and B (2), and a new chromone, haworforbin C (3), have been isolated from Haworthia cymbiformis. Their structures and absolute configurations were elucidated on the basis of NMR and CD data. Haworforbin C (3) exhibited moderate inhibition of nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cell line.

Haworforbins A–C, new phenolics from Haworthia cymbiformis

Six new diterpenoids, sabiperones A—F (1—6) have been isolated from the aerial part of Juniperus sabina. Their structures were elucidated by spectroscopic methods including 2D NMR techniques. Sabiperone F showed moderate cell growth inhibitory activities against five human cancer cell lines.

Sabiperones A-F, new diterpenoids from Juniperus sabina.

A new Cephalotaxus alkaloid, cephastigiamide A (1), has been isolated from the leaves of Cephalotaxus harringtonia forma fastigiata and the structure was elucidated by 2D NMR analysis and chemical degradation. Harringtonine, deoxyharringtonine, and homodeoxyharringtonine showed pronounced antiplasmodial activity against Plasmodium falciparum 3D7 but not against Leishmania major. Structure-activity relationship for antiplasmodial activity of isolated Cephalotaxus alkaloids was also discussed.

Cephastigiamide A, and antiplasmodial activity of Cephalotaxus alkaloids from Cephalotaxus harringtonia forma fastigiata

Two new taxoids, taxezopidines M (1) and N (2), have been isolated from seeds of the Japanese yew, Taxus cuspidata, and new structures were elucidated on the basis of spectroscopic data. The absolute configuration of a 3-N,N-(dimethylamino)-3-phenylpropanoyl group in 1 and 2 was determined to be R in each case by chiral HPLC analysis. The effect of 1 and 2 on the CaCl(2)-induced depolymerization of microtubules was investigated.

Taxezopidines M and N, taxoids from the Japanese yew, Taxus cuspidata.

Bioactivity guided separation of Reinwardtiodendron cinereum barks methanol extract led to the isolation of two new onocerane triterpenoids, reinereins A and B (1 and 2), together with three known onocerane triterpenoids. Their structures were elucidated on the basis of NMR spectroscopic data. In vitro cytotoxic activities of the isolated compounds against several type of cancer cells were evaluated.

Yusuke Hirasawa

Papers

Haworforbins A–C, new phenolics from Haworthia cymbiformis

Sabiperones A-F, new diterpenoids from Juniperus sabina.

Cephastigiamide A, and antiplasmodial activity of Cephalotaxus alkaloids from Cephalotaxus harringtonia forma fastigiata

Taxezopidines M and N, taxoids from the Japanese yew, Taxus cuspidata.

Reinereins A and B, new onocerane triterpenoids from Reinwardtiodendron cinereum