ABSTRACT
A total of 12 compounds were synthesized from the natural sesquiterpene (-) drimenol (compounds 4 to 15). The synthesized compounds corresponded to N-phenyl-driman-9-carboxamide derivatives, similar to some fungicides that inhibit the electron-transport chain. Their structures were characterized and confirmed by 1H NMR, 13C NMR spectroscopy, and mass spectrometry. Compounds 5 to 15 corresponded to novel compounds. The effect of the compounds on the mycelial growth of Botrytis cinerea was evaluated. Methoxylated and chlorinated compounds in the aromatic ring (compounds 6, 7, 12, and 13) exhibited the highest antifungal activity with IC50 values between 0.20 and 0.26 mM. On the other hand, the effect on conidial germination of B. cinerea of one methoxylated compound (6) and one chlorinated compound (7) was analyzed, and no inhibition was observed. Additionally, compound 7 decreased 36% the rate of oxygen consumption by germinating conidia.
ABSTRACT
Several reviews have been published on sesquiterpenes, and on drimane-type sesquiterpenes, going through drimenol and related compounds among others. However, to our knowledge, this is the first review exclusively on drimenol. Although, the main focus is on drimenol as a synthon for other drimane-type compounds, synthetic routes to obtain racemic and (-)-drimenol are summarized, as well as its isolation and determination of its configuration, in the early fifties. The reviewed synthetic routes start from natural (-)-drimenol as chiral synthon in most of cases, nevertheless total syntheses are considered as well. The strategies where racemic drimenol is involved begin with biomimetic cyclization of trans-farnesol. Microbiological procedures to functionalize the A ring of drimenol are also commented. The revision is classified according to the chemical structure of the final product, which mainly correspond to structures of natural occurrence, although other related derivatives are also analyzed.
Subject(s)
Terpenes/chemical synthesis , Biomimetics , Farnesol/chemistry , Hydroxylation , Polycyclic Sesquiterpenes , Terpenes/chemistry , Terpenes/metabolismABSTRACT
Polygodial (1) and its derivatives acetal 2 (propylene) and 3 (ethylene) were prepared and their antifeedant activity and toxic effects evaluated on several insect species with different feeding ecologies (Spodoptera littoralis, Leptinotarsa decemlineata, Myzus persicae and Rhopalosiphum padi) along with that of polygonone (4). We also tested their selective cytotoxic effects on insect-derived (Spodoptera frugiperda ovarian Sf9 cells) and mammalian Chinese hamster ovary (CHO) cells. The antifeedant activity of these compounds was consistent with the proposed mode of action for antifeedant drimanes, i. e. adduct formation with amino groups for M. persicae and R. padi (dialdehyde > ketoaldehyde > aldehydeacetal). This was not the case for L. decemlineata, and the cytotoxic effects on insect-derived Sf9 and mammalian CHO cells (aldehydeacetal > dialdehyde > ketoaldehyde).
Subject(s)
Insecta/growth & development , Larva/drug effects , Sesquiterpenes/pharmacology , Animal Feed , Animals , Appetite Depressants/chemistry , Appetite Depressants/pharmacology , Insecta/drug effects , Models, Molecular , Molecular Conformation , Plants/parasitology , Sesquiterpenes/chemistryABSTRACT
13C chemical shift assignment of several methyl substituted heterocyclic naphtho- and anthraquinones, including dihydronaphthofuranquinones, azaanthraquinones, benzopyrroloquinolinediones and benzothiophenoquinolinediones, are described. A deshielding effect due to a methyl group was observed over the neighbouring carbonyl carbon, in every case studied. 13C assignments were based on 2D experiments.
Subject(s)
Anthraquinones/chemistry , Carbon/chemistry , Magnetic Resonance Spectroscopy , Naphthoquinones/chemistry , Anthraquinones/chemical synthesis , Carbon Isotopes , Naphthoquinones/chemical synthesisABSTRACT
Derivatives of natural quinones with biological activities, such as lapachol, alpha- and beta-lapachones, have been synthesized and their trypanocidal activity evaluated in vitro in Trypanosoma cruzi cells. All tested compounds inhibited epimastigote growth and trypomastigote viability. Several compounds showed similar or higher activity as compared with current trypanocidal drugs, nifurtimox and benznidazole. The results presented here show that the anti-T. cruzi activity of the alpha-lapachone derivatives can be increased by the replacement of the benzene ring by a pyridine moiety. Free radical production and consequently oxidative stress through redox cycling or production of electrophilic metabolites are the potential biological mechanism of action for these synthetic quinones.
Subject(s)
Naphthoquinones/chemical synthesis , Naphthoquinones/pharmacology , Trypanocidal Agents/chemical synthesis , Trypanocidal Agents/pharmacology , Trypanosoma cruzi/drug effects , Animals , Molecular Structure , Naphthoquinones/chemistry , Oxidation-Reduction , Stereoisomerism , Trypanocidal Agents/chemistryABSTRACT
Epoxidation of argentilactone (1) with m-chloroperbenzoic acid gave a diasteromeric mixture of 2 and 3 in a ratio 1.8 : 1, with total yield 60%. The configuration of 7,8-oxirane ring for both diasteromers was determined by NMR analysis. Reaction of 1 with urea hydrogen peroxide gave the 3,4-epoxide (4) in 65% yield. The in vitro activity of 2, 3, 4 and argentilactone against Leishmania amazonensis was tested, only epoxides (2) and (3) showed leishmanicidal effect.
Subject(s)
Antiprotozoal Agents/pharmacology , Epoxy Compounds/chemistry , Epoxy Compounds/pharmacology , Lactones/chemistry , Lactones/pharmacology , Leishmania/drug effects , Animals , Molecular StructureABSTRACT
An efficient and highly stereoselective synthesis of cytotoxic 8-epipuupehedione (1b) was achieved starting from natural (-)-drimenol (6). The key step to obtain stereoselectivity was the simultaneous demethylation and oxidation of the dihydrobenzopyran methoxy derivatives 10a and 10b.
