Diterpenoids of terrestrial origin.

Covering January to December 2017; previous review Nat. Prod. Rep., 2017, 34, 1233-1243. This review covers the isolation and chemistry of diterpenoids from terrestrial as opposed to marine sources and includes labdanes, clerodanes, abietanes, pimaranes, kauranes, cembranes and their cyclization products. There are 228 references.

Structural and biosynthetic studies on eremophilenols related to the phytoalexin capsidiol, produced by Botrytis cinerea.

A thorough study of the fermentation broth of three strains of Botrytis cinerea which were grown on a modified Czapek-Dox medium supplemented with 5 ppm copper sulphate, yielded five undescribed metabolites. These metabolites possessed a sesquiterpenoid (+)-4-epi-eremophil-9-ene carbon skeleton which was enantiomeric to that of the phytoalexin, capsidiol. The isolation of these metabolites when the fungus was stressed, suggests that they may be potential effectors used by B. cinerea to circumvent plant chemical defences against phytopathogenic fungi. The biosynthesis of these compounds has been studied using 2H and 13C labelled acetate.

Relevance of the deletion of the Tatri4 gene in the secondary metabolome of Trichoderma arundinaceum.

The fungus Trichoderma arundinaceum (Ta37) has a significant biocontrol application which has been related to the production of the trichothecene, harzianum A (2). Previous studies with a strain of T. arundinaceum which was blocked for the production of 2, revealed the existence of a chemical cross-regulation between the biocontrol fungus and its target organism. A study of the secondary metabolome of a single culture of a mutant of T. arundinaceum TaΔTri4 which produces trichothecene biosynthetic intermediates, has now been carried out. The production of secondary metabolites in a co-culture with the phytopathogen, Botrytis cinerea, was then analyzed. The mutant produced a larger quantity of the aspinolides B (6) and C (7) and other derivatives when compared to the wild type Ta37. Ten new metabolites were isolated: three aspinolides 12-14, the γ-lactones 15 and 16, two hemi-ketals 17 and 18 and three aspinolide degradation products, 19, 21 and 22. In the confrontation cultures involving the TaΔTri4 and the B. cinerea B05.10 strains, there was a higher production of the aspinolides B and C by the TaΔTri4 mutant while the production of the botryanes and botcinins by B. cinerea was reduced in the area of interaction between the cultures. These results shed light on the chemical cross-talk and ecological interactions between these fungi.

Diterpenoids of terrestrial origin.

Covering: January to December, 2016 previous review Nat. Prod. Rep., 2016, 33, 1227-1238This review covers the isolation and chemistry of diterpenoids from terrestrial as opposed to marine sources and includes labdanes, clerodanes, abietanes, pimaranes, kauranes, cembrenes and their cyclization products. There are 205 references.

A hundred years in the elucidation of the structures of natural products.

The development in the strategies for elucidating the structures of natural products from 1916 to 2016 are reviewed revealing the transition from chemical to spectroscopic methods and using examples drawn from the chemistry of terpenoids and steroids.

Some contributions of organic chemistry to the study of the biosynthesis of natural products.

The development over the last 100 years of organic chemists' contributions to the understanding of the biosynthesis of natural products is reviewed. The transitions from speculation to labelling experiments and to the current role of genomics are exemplified, particularly from terpenoid biosynthesis.

The formation of sesquiterpenoid presilphiperfolane and cameroonane metabolites in the Bcbot4 null mutant of Botrytis cinerea.

Botrytis cinerea is a polyphagous fungal parasite which causes serious damage to more than 200 plant species and consequent economic losses for commercial crops. This pathogen produces two families of phytotoxins, the botryanes and botcinins, which are involved in the infection mechanism. The B. cinerea genome has provided a complete picture of the genes involved in the biosynthesis of its secondary metabolites. The botrydial biosynthetic gene cluster has been identified. This cluster consists of seven genes, where the genes BcBOT1, BcBOT3 and BcBOT4 encode three mono-oxygenases. A study of the Bcbot4Δ null mutant revealed that this mono-oxygenase was involved in the hydroxylation at C-4 of the probotryane skeleton (C-11 of the presilphiperfolane skeleton). A detailed study of the Bcbot4Δ null mutant has been undertaken in order to study the metabolic fate of the presilphiperfolan-8-ol intermediate biosynthesized by this organism and in particular by this strain. As a result three new presilphiperfolanes and three new cameroonanes have been identified. The results suggest that the absence of the oxygen function at C-11 of the presilphiperfolane skeleton permits rearrangement to a cameroonane whilst hydroxylation at C-11 precludes this rearrangement. It is possible that the interactions of the C-11 hydroxylated derivatives perturb the stereo-electronic requirements for the migration of the C-11:C-7 sigma bond to C-8.

Mild Epoxidation of Allylic Alcohols Catalyzed by Titanium(III) Complexes: Selectivity and Mechanism.

A novel methodology for the epoxidation of a broad range of primary, secondary, and tertiary allylic alcohols is described using tert-butyl hydroperoxide as oxidant and Ti(III) species generated by reduction of Ti(IV) complexes, with manganese (0) in 1,4-dioxane under mild reaction conditions. The reaction proceeded with wide substrate scope and high chemo- and diastereoselectivity. A mechanistic pathway for the reaction is also discussed.

Efficient O-Acylation of Alcohols and Phenol Using Cp2TiCl as a Reaction Promoter.

A method has been developed for the conversion of primary, secondary, and tertiary alcohols, and phenol, into the corresponding esters at room temperature. The method uses a titanium(III) species generated from a substoichiometric amount of titanocene dichloride together with manganese(0) as a reductant, as well as methylene diiodide. It involves a transesterification from an ethyl ester, or a reaction with an acyl chloride. A radical mechanism is proposed for these transformations.

Genetic and Molecular Basis of Botrydial Biosynthesis: Connecting Cytochrome P450-Encoding Genes to Biosynthetic Intermediates.

Over two hundred species of plants can be infected by the phytopathogenic fungus Botrytis cinerea under a range of different environmental conditions. In response to these, the fungus produces unique terpenoid and polyketide metabolites. Parts of the plants may be killed by the phytotoxin botrydial, enabling the fungus to feed on the dead cells. In this paper, we describe the genetic and molecular basis of botrydial biosynthesis and the function of the five genes of the genome of B. cinerea that together constitute the botrydial biosynthetic gene cluster. Genes BcBOT3 and BcBOT4, encoding two cytochrome P450 monooxygenases, were inactivated by homologous recombination and were shown to catalyze regio- and stereospecific hydroxylations at the carbons C-10 and C-4, respectively, of the presilphiperfolan-8ß-ol skeleton. The null mutants, bcbot3Δ and bcbot4Δ, accumulated key intermediates in the botrydial biosynthesis enabling the complete genetic and molecular basis of the botrydial biosynthetic pathway to be established. Furthermore, the bcbot4Δ mutant overproduced a significant number of polyketides, which included, in addition to known botcinins, botrylactones and cinbotolide A, two new botrylactones and two new cinbotolides, cinbotolides B and C.

Diterpenoids of terrestrial origin.

Covering January to December 2015. Previous review; Nat. Prod. Rep., 2015, 32, 1654-1663.This review covers the isolation and chemistry of diterpenoids from terrestrial as opposed to marine sources and includes labdanes, clerodanes, abietanes, pimaranes, kauranes, cembranes and their cyclization products. There are 214 references.

Rosemary, the beneficial chemistry of a garden herb.

The major natural products that are present in the garden herb, rosemary (Rosmarinus officinalis) including the mono di- and triterpenoid, flavonoid and phenolic constituents together with their biological activity as anti-microbial, anti-oxidant, anti-inflammatory, memory-enhancing and tumour-inhibitory agents, are reviewed.

Chemically Induced Cryptic Sesquiterpenoids and Expression of Sesquiterpene Cyclases in Botrytis cinerea Revealed New Sporogenic (+)-4-Epieremophil-9-en-11-ols.

The sequencing of the genomes of the B05.10 and T4 strains of the fungus Botrytis cinerea revealed an abundance of novel biosynthetic gene clusters, the majority of which were unexpected on the basis of the previous analyses of the fermentation of these and closely related species. By systematic alteration of easy accessible cultivation parameters, using chemical induction with copper sulfate, we have found a cryptic sesquiterpenoid family with new structures related to eremophil-9-ene, which had the basic structure of the sesquiterpene (+)-5-epiaristolochene ((+)-4-epieremophil-9-ene). An expression study of the sesquiterpene cyclase genes present in the Botrytis cinerea genome, under culture conditions, is reported. In general, a 3 day delay and a higher BcSTC genes expression were observed when copper (5 ppm) was fed to the fermentation broth. In addition, to the observed effect on the BcBOT2 (BcSTC1) gene, involved in the biosynthesis of the botrydial toxin, a higher expression level for BcSTC3 and BcSTC4 was observed with respect to the control in the strain B05.10. Interestingly, under copper conditions, the BcSTC4 gene was the most expressed gene in the Botrytis cinerea UCA992 strain. In vitro evaluation of the biological role of these metabolites indicates that they contributed to the conidial development in B. cinerea and appear to be involved in self-regulation of the production of asexual spores. Furthermore, they promoted the formation of complex appressoria or infection cushions.

From Caá-ehé to a commercial sweetener - the diterpenoid glycosides of Stevia rebaudiana.

The isolation, structure elucidation, chemistry, biosynthesis and biological activity of the sweet steviol glycosides from Stevia rebaudiana, are reviewed.

From 'mad honey' to hypotensive agents, the grayanoid diterpenes.

The toxicity of Rhododendron species and other members of the Ericaceae which is due to the grayanoid diterpenes, is described. Their structures, biogenesis and biological activity is reviewed.

Sir John and Lady Rita Cornforth: a distinguished chemical partnership.

This review describes the life of Sir John Cornforth AC CBE FRS, who was awarded the Nobel Prize for Chemistry in 1975. It covers his early life in Australia, his work in Oxford, the National Institute for Medical Research, the Milstead Laboratory of Chemical Enzymology and the University of Sussex, together with the contributions made by his wife, Lady Rita Cornforth.

Sir John Cornforth AC CBE FRS: his synthetic work.

Sir John Cornforth work on the synthesis of cholesterolandpenicillamine, on the chemistry of oxazoles, the stereochemistry of the synthesis of alkenes, the synthesis of abscisic acid and of dibenzophospholes as mimics of enzyme action, is reviewed.

Sir John Cornforth AC CBE FRS: his biosynthetic work.

Sir John Cornforth's work on the stereochemistry of enzyme reactions involved in the biosynthesis of squalene and cholesterol and in the formation and metabolism of a chiral methyl group in acetyl co-enzyme A, is reviewed.

Diterpenoids of terrestrial origin.

Covering January to December 2014. Previous review, Nat. Prod. Rep., 2015, 32, 76-87 This review covers the isolation and chemistry of diterpenoids from terrestrial as opposed to marine sources and includes, labdanes, clerodanes, abietanes, pimaranes, kauranes, cembranes and their cyclization products. There are 200 references.

Current strategies for the elucidation of the structures of natural products.

The application of the results from various physical methods to the isolation, characterisation and elucidation of the structures and stereochemistry of natural products is reviewed.