Transformações químicas, caracterizações e estudo de modelagem molecular do clerodano bioativo trans-desidrocrotonina

In this work it were developed synthetic and theoretical studies for clerodane-type diterpenes obtained from Croton cajucara Benth which represents one of the most important medicinal plant of the Brazil amazon region. Specifically, the majoritary biocompound 19-nor-clerodane trans-dehydrocrotonin (t-DCTN) isolated from the bark of this Croton, was used as target molecule. Semi-synthetic derivatives were obtained from t-DCTN by using the followed synthetic procedures: 1) catalytic reduction with H2, 2) reduction using NaBH4 and 3) reduction using NaBH4/CeCl3. The semi-synthetic 19-nor-furan-clerodane alcohol-type derivatives were denominated such as t-CTN, tCTN-OL, t-CTN-OL, t-DCTN-OL, t-DCTN-OL, being all of them characterized by NMR. The furan-clerodane alcohol derivatives t-CTN-OL and tCTN-OL were obtained form the semi-synthetic t-CTN, which can be isolated from the bark of C. cajucara. A theoretical protocol (DFT/B3LYP) involving the prevision of geometric and magnetic properties such as bond length and angles, as well as chemical shifts and coupling constants, were developed for the target t-DCTN in which was correlated NMR theoretical data with structural data, with satisfactory correlation with NMR experimental data (coefficients ranging from 0.97 and 0.99) and X-ray diffraction data. This theoretical methodology was also validated for all semi-synthetic derivatives described in this work. In addition, topological data from the Quantum Theory of Atoms in Molecules (QTAIM) showed the presence of H-H and (C)O--H(C) intramolecular stabilized interactions types for t-DCTN e t-CTN, contributing to the understanding of the different reactivity of this clerodanes in the presence of NaBH4.

Tetranorclerodanes and clerodane-type diterpene glycosides from Dicranopteris dichotoma

The acetone extract of Dicranopteris dichotoma afforded two new tetranorclerodanes, 18-hydroxyaylthonic acid (1) and 18-oxo-aylthonic acid (2), and four new clerodane-type diterpene glycosides, (6S,13S)-6-O-[6-O-acetyl-beta-D-glucopyranosyl-(1 -> 4)-alpha

Salvia divinorum: an hallucinogenic mint which might become a new recreational drug in Switzerland.

Salvia divinorum Epling & Jativa is an hallucinogenic mint traditionally used for curing and divination by the Mazatec Indians of Oaxaca, Mexico. Young people from Mexican cities were reported to smoke dried leaves of S. divinorum as a marijuana substitute. Recently, two S. divinorum specimens were seized in a large-scale illicit in-door and out-door hemp plantation. Salvinorin A also called divinorin A, a trans-neoclerodane diterpene, was identified in several organic solvent extracts by gas chromatography-mass spectrometry. The botanical identity of the plant was confirmed by comparing it to an authentic herbarium specimen. More plants were then discovered in Swiss horticulturists greenhouses. All these data taken together suggest that many attempts exist in Switzerland to use S. divinorum as a recreational drug. This phenomenon may be enhanced because neither the magic mint, nor its active compound are banned substances listed in the Swiss narcotic law.

Rearranged (4 -> 2)-abeo-clerodane and clerodane diterpenes from Aristolochia chamissonis

From stems of Aristolochia chamissonis Duch., five new diterpenes, one rearranged (4 --> 2)-abeo-clerodane and four ent-clerodanes, were isolated. Their structures were determined to be (+)-(4 --> 2)-abeo-kolavelool-3-oic acid, (-)-13-epi-2-oxokolavelool, (-)-2 beta-hydroxykolavelool, (-)-2 beta-hydroperoxykolavelool and (+)- 13-epi-2 alpha-hydroxykolavelool. In addition, lignans, sesquiterpenes, steroids and two known ent-clerodane diterpenes were isolated. (C) 1998 Elsevier B.V. Ltd. All rights reserved.

Clerodane diterpenes from Aristolochia species

The investigation of Aristolochia brasiliensis and A. esperanzae afforded 12 clerodane derivatives, including the following six novel ones: rel (5S, 8R, 9S, 10R)-2-oxo-ent-3-cleroden-15-oic acid, rel (5S, 8R, 9S, 10R)-2-oxo-ent-clerod-3,13-dien-15-oic acid methyl ester, (5R, 8R, 9S, 10R)-ent-3-cleroden-15-oic acid, rel (5S, 8R, 9S, 10R)-ent-clerod-3,13-dien-15-oic acid, (2S, 5R, 8R, 9S, 10R)-2-hydroperoxy-ent-3-cleroden-15-oic acid methyl ester and (2S, 5R, 8R, 9S, 10R)-2-hydroperoxy-ent-clerod-3,13-dien-15-oic acid methyl ester. The structures were assigned on the basis of spectral data and derivatization by chemical reactions. The occurrence of this type of diterpene has not previously been reported in Aristolochiaceae. © 1987.

Desorption electrospray ionisation mass spectrometry reveals in situ modification of a hindered amine light stabiliser resulting from direct N–OR bond cleavage

Detection and characterisation of structural modifications of a hindered amine light stabiliser (HALS) directly from a polyester-based coil coating have been achieved by desorption electrospray ionisation mass spectrometry (DESI-MS) for the first time. In situ detection is made possible by exposing the coating to an acetone vapour atmosphere prior to analysis. This is a gentle and non-destructive treatment that allows diffusion of analyte to the surface without promoting lateral migration. Using this approach a major structural modification of the HALS TINUVIN®123 (bis(1-octyloxy-2,2,6,6-tetramethyl-4-piperidyl) sebacate) was discovered where one N-ether piperidine moiety (N-OC8H17) is converted to a secondary piperidine (N–H). With the use of 2-dimensional DESI-MS imaging the modification was observed to arise during high curing temperatures (ca. 260 °C) and under simulated physiological conditions (80 °C, full solar spectrum). It is proposed that the secondary piperidine derivative is a result of a highly reactive aminyl radical intermediate produced by N–O homolytic bond cleavage. The nature of the bond cleavage is also suggested by ESR spin-trapping experiments employing α-phenyl-N-tert-butyl nitrone (PBN) in toluene at 80 °C. The presence of a secondary piperidine derivative in situ and the implication of N–OR competing with NO–R bond cleavage suggest an alternative pathway for generation of the nitroxyl radical—an essential requirement in anti-oxidant activity that has not previously been described for the N-ether sub-class of HALS.

Conformational flexibility in androgenic steroids - the structure of a new form of (+)-17-beta-hydroxy-19-nor-4-androsten-3-one (19-nortestosterone), c18h26o2

The structure and conformation of a second crystalline modification of 19-nortestosterone has been determined by X-ray methods. M r = 274, monoclinic P2 l, a=9.755(2), b= 11.467(3), c= 14.196(3)/L fl=101.07(2) ° , V=1558.4 (8) A 3, Z=4, Ox= I. 168 g cm -3, Mo Ka, 2 = 0.7107 ,/k, ~ = 0.80 cm -l, F(000) = 600, T= 300 K. R = 0.060 for 2158 observed reflections. The two molecules in the asymmetric unit show significant differences in the A-ring conformation from that of the previously reported form of the title compound [Precigoux, Busetta, Courseille & Hospital (1975). Acta Cryst. B31, 1527-1532]. The l a,2fl-half-chair conformation of the A ring increases its conformational freedom compared with testosterone.

Nitrification (DMPP) and urease (NBPT) inhibitors had no effect on pasture yield, nitrous oxide emissions nor nitrate leaching under irrigation in a hot-dry climate

Modern dairy farming in Australia relies on substantial inputs of fertiliser nitrogen (N) to underpin economic production. However, N lost from dairy systems represents an opportunity cost and can pose a number of environmental risks. Nitrogen cycle inhibitors can be co-applied with N fertilisers to slow the conversion of urea to NH4+ to reduce losses via volatilisation, and slow the conversion of NH4+ to NO3- to minimize leaching of NO3- and gaseous losses via nitrification and denitrification. In a field campaign in a high input ryegrass-kikuyu pasture system we compared the soil N pools, losses and pasture production between a) urea coated with the nitrification inhibitor (3,4-dimethyl pyrazole phosphate - DMPP) b) urea coated with the urease inhibitor (N-(n-butyl) thiophosphoric triamide - NBPT) and c) standard urea. There was no treatment effect (P>0.05) on soil mineral N, pasture yield, N2O flux nor leaching of NO3- cf. standard urea. We hypothesise that at our site, because gaseous losses were highly episodic (rainfall was erratic and displayed no seasonal rainfall nor soil wetting pattern) that there was a lack of coincidence of N application and conditions conducive to gaseous losses, thus the effectiveness of the inhibitor products was minimal and did not result in an increase in pasture yield. There remains a paucity of knowledge on N cycle inhibitors in relation to their effective use in field system to increase N use efficiency. Further research is required to define under what field conditions inhibitor products are effective in order to be able to provide accurate advice to managers of nitrogen in production systems.

Enantiospecific synthesis of ABC-ring system of A-nor and abeo 4(3 -> 2) tetra and pentacyclic triterpenes

Enantiospecific synthesis of ABC-ring systems of A-nor and abeo 4(3 -> 2) tetra and pentacyclic triterpenes has been accomplished starting from the readily available monoterpene (R)-carvone. (R)-Carvone was used as the B-ring of the target molecules. A lithium-liquid ammonia mediated cyclisation of delta,epsilon-unsaturated ester was employed for the cyclopentannulation at the C-5 and C-6 carbons of carvone and an RCM reaction was employed for the cyclohexannulation to generate the ABC-ring system of A-nor tetra and pentacyclic triterpenes. The strategy has been extended for the synthesis of the ABC-ring system of abeo 4(3 -> 2) tetra and pentacyclic triterpenes. (C) 2009 Elsevier Ltd. All rights reserved.

Syntheses of the trans,meso- and racemic C11 acids, degradation products of diterpene acids

Syntheses of the isomers of the C11 acid, 1(a),3(a)- dimethylcyclohexane-1 (e),2(e),3(e)-tricarboxylic acid (A) and 1(a),3(e)-dimethylcyclohexane-1(e),2(e),3(a)-tricarboxylic acid (B), the latter by two different routes, are reported. Two of the four possible isomers of the precursor triester, trimethyl 1-methylcyclohexane-1,2,3-tricarboxylate, on individual methylation followed by hydrolysis, gave the trans,meso-acid (A), identified by comparison with an authentic sample, and the cis,trans-form (B) whose structure and configuration were proved by comparison with a specimen obtained by the unambiguous and highly stereoselective second synthesis. This demonstrated that methylation of the triester isomers occurs stereospecifically and exclusively at C-3. In the second sequence, it has been possible to assign definite conformations to four key intermediates and the final product, directly from n.m.r. spectra, from changes in these spectra accompanying specific steps, and from chemical evidence. Comparison of the n.m.r. spectra of the isomeric triesters (A) and (B) has provided unequivocal proof of the accepted trans,meso configuration for the abietic acid degradation product (A).

Synthesis based on cyclohexadienes: Part 30 - Syntheses of 2-nor-cedrene and some analogues of funebrene

A novel method for the construction of tricyclo[5.3.1.0(1,5)]undecane and tricyclo[6.3.1.0(1,6)]dodecane frame work has been developed. Thus the alcohols 6, 18, 21 and 29 undergo Lewis acid-catalysed rearrangement to the tricyclic ketones 5, 19, 22 and 30. Dehydrogenation of 22 to the enone 23 proves the synchronous anti-migration of the methanobridge during the skeletal rearrangement. Finally, one carbon homologation of the ketones 5 and 19 leads to the syntheses of 2-norcedrene 4 and some analogues of funebrene 20 and 30.

On the existence of a nickel hydroxide phase which is neither alpha nor beta

A novel phase of nickel hydroxide with an average interlayer spacing 5.4-5.6 Angstrom has been synthesized which is neither ct nor beta type but is an interstratification of both. It ages to the beta form in strong alkali. These observations have implications on the dissolution-reprecipitation mechanism suggested for the alpha-->beta transformation of nickel hydroxide.

An Enantiospecific Formal Total Synthesis of the 5-8-5 Tricyclic Diterpene ent-Fusicoauritone

An enantiospecific formal total synthesis of the 5-8-5 tricyclic diterpene fusicoauritone has been accomplished, starting from 5-isopropyl-2-methylcyclopent-1-enemethanol [available in three steps from (R)-dihydrolimonene] employing two ring-closing-metathesis reactions for the construction of the eight- and five-membered rings.