Absolute configuration of trixanolides from Trixis pallida.

The aerial parts of Trixis pallida afforded seven known trixanolides (18-24) together with 17 new trixanolides (1-17). Their structures were determined by 1D and 2D NMR techniques, while the absolute configuration of the trixane skeleton was determined using the Mosher method and turned out to be enantiomeric to that reported using the Horeau method. This result is further discussed from the biosynthetic point of view.

Antimicrobial activity of three Mexican Gnaphalium species.

The antibacterial activity of the hexane, ethyl acetate and methanol extracts of the flowers, leaves and stems of Gnaphalium oxyphyllum var. oxyphyllum, G. liebmannii var. monticola and G. viscosum was investigated. The hexane extracts showed in all cases the higher inhibitions, G. oxyphyllum flower extract exhibiting the wider spectrum of activity.

Total syntheses of five indole alkaloids from the marine bryozoan Flustra foliacea.

A general, efficient, and conceptually new approach to the total syntheses of marine-derived indole alkaloids, including (+/-)-flustramines A (1) and B (2), (+/-)-flustramides A (3) and B (4), and (+/-)-debromoflustramine B (5), is outlined. The key step in the syntheses involves the conjugated addition of an organomagnesium species derived from prenyl bromide to 2-hydroxyindolenines. Compounds 1, 2, and 5 have been synthesized in five steps with 23%, 17%, and 16% overall yield, respectively, whereas flustramides 3 and 4 have been synthesized in only four steps with 24% and 18% overall yield, respectively, on the basis of 2-hydroxyindolenines.

Cacalolides from Senecio madagascariensis.

14-Isovaleryloxy-O-methyl-1,2-dehydrocacalol (1) and cycloart-23-ene-3,25-diol, beta-sitosterol, and stigmasterol, along with five new cacalolides, 1-hydroxy-2-methoxy-1,2,3,4-dehydro-6-dehydroxycacalone (2), 1-hydroxy-2-methoxy-1,2,3,4-dehydrocacalone (3), 1,2-dimethoxy-1,2,3,4-dehydro-6-dehydroxycacalone (4), 1,2-dimethoxy-1,2,3,4-dehydrocacalone (5), and 2-methoxy-O-methyl-1-oxo-2,3-dehydrocacalol (6), were isolated from Senecio madagascariensis collected from Colombia. The structures of the new compounds were determined using one- and two-dimensional NMR techniques. In addition, the structure of 2 was corroborated by derivatizations and single-crystal X-ray diffraction studies.

Germacranolides and a new type of guaianolide from Acanthospermum hispidum.

The aerial parts of an Argentinian collection of Acanthospermum hispidum afforded 26 sesquiterpene lactones, including the two guaianolides (1 and 2) having a novel oxygen bridge between C-4 and C-14, three new cis,cis-germacranolides (4, 7, and 8), and two new melampolides (25 and 26). Guaianolides 1 and 2 seem to derive biosynthetically from the germacranolide 27 having the (1)D(14, 15)D(5) conformation. The structures were elucidated using extensive spectroscopic analysis.

A glycosidic eudesmanolide from Hyaloseris salicifolia.

The flowers of Hyaloseris salicifolia afforded known ivasperin, while the leaves afforded ivasperin and 2-O-(6'-O-acetyl-beta-D-glucopyranosyl)-ivasperin, whose structure was determined by spectroscopic methods.

Three new diterpenoids based on the novel sarcopetalane skeleton from Croton sarcopetalus.

The roots of Croton sarcopetalus afforded three new diterpenoids (2-4) with a novel carbon skeleton that seems to be derived biosynthetically from a pimarane precursor. The essential oil of the roots gave trans-methylisoeugenol as the main constituent, along with 22 further compounds.

Grindelane diterpenoids from Stevia subpubescens.

Four new 9R,13R-epoxylabdane diterpenes (1-4) and a known clerodane derivative, 3,4beta-epoxy-5beta,10beta-cis-17alpha, 20alpha-clerod-13(14)-en-15,16-olide, were isolated from the leaves of Stevia subpubescens. The structures, which correspond to the grindelane class of diterpenoids, were elucidated by NMR data, chemical correlation, and single-crystal X-ray diffraction analysis of monoacetate 5. The absolute configuration of 1-4 is based on the optical activity of ketone 3 as compared with data of closely related substances.

Longipinane derivatives from Stevia connata.

The hexane extracts of the roots of Stevia connata afforded three new longipinene derivatives, longipinane-7beta,8alpha, 9alpha-triol-1-one 7-angelate-8-methylbutyrate (1), longipin-2-ene-7beta,8alpha,9alpha-triol-1-one 8,9-diangelate (6), and longipin-2-ene-7beta,8alpha,9alpha-triol-1-one 8-angelate-9-methylbutyrate (8), together with the known longipinane-7beta,8alpha,9alpha-triol-1-one 8,9-diangelate (2), longipinane-7beta,8alpha,9alpha-triol-1-one 7,9-diangelate (3), longipinane-7beta,8alpha,9alpha-triol-1-one 7,8-diangelate (4), longipin-2-ene-7beta,8alpha,9alpha-triol-1-one 7,8-diangelate (5), longipin-2-ene-7beta,8alpha,9alpha-triol-1-one 7-angelate-8-methylbutyrate (12), and stigmasterol. The structures of the new compounds were determined by chemical transformations and spectral methods including 2D NMR measurements. Spontaneous intramolecular transesterifications starting from the 8-angelate-9-methylbutyrate 8 provided an equilibrated mixture of the 7-angelate-9-methylbutyrate 10, the 7-angelate-8-methylbutyrate 12 and the starting material when stored in MeOH-H(2)O solution, while the 8,9-diangelate 6 only provided a binary mixture of the 7, 9-diangelate 7 and the starting material under the same conditions. The structures of 6-8, 10, and 12 and those of the nonisolable reaction intermediates 9, 11, and 14 were further evaluated by AM1 semiempirical calculations.

Mass spectral studies of methoxynaphthoflavones

The electron impact induced fragmentations of seven methoxynaphthoflavones have been studied with the aid of low- and high-resolution measurements, metastable decompositions and isotope labelling using carbon-13 atoms. The retro Diels-Alder cleavage of the methoxynaphthoflavones is strongly influenced by the substituent position providing in most cases intact A- and B-ring fragments. The intensity ratio of these ring fragments appears to be very sensitive to the charge distribution within the parent ion. Copyright -Copyright 1999 John Wiley & Sons, Ltd.

Synthesis and absolute configuration of (S)-(-)- and (R)-(+)-2, 3-dihydro-2-(1-methylethenyl)-6-methoxybenzofuran

Resolution of racemic 2,3-dihydro-2-carboxy-6-methoxybenzofuran (2) by recrystallizations of diastereomeric salts prepared with (S)-(-)-alpha-methylbenzylamine and (R)-(+)-alpha-methylbenzylamine gave the starting materials for the four-step total syntheses of (S)-(-)-2,3-dihydro-2-(1-methylethenyl)-6-methoxybenzofuran (1a) and (R)-(+)-2,3-dihydro-2-(1-methylethenyl)-6-methoxybenzofuran (1b). Their absolute configuration was established by chemical correlation.

Isolation, total synthesis, and relative stereochemistry of a dihydrofurocoumarin from dorstenia contrajerva

The roots of Dorstenia contrajerva afforded the dihydrofurocoumarin 1b whose identity was determined from NMR spectral data of the derived acetate 7b combined with the total syntheses of 1a and 1b, which were carried out in five steps with 19% overall yield, starting from 2,3-dihydro-2-isopropenyl-6-methoxybenzofuran (2). The relative stereochemistry of 7b was determined from a single-crystal X-ray diffraction study as (2S,1'S)-2, 3-dihydro-2-(1'-hydroxy-1'-acetyloxymethylethyl)-7H-furo[3, 2g][1]benzopyran-7-one.

Synthesis of 3-amino-2-(3-indolyl)propanol and propanoate derivatives and preliminary cardiovascular evaluation in rats.

A series of tryptamine analogues has been prepared and tested for their 5-HT1 receptor agonist properties. The incorporation of an alkoxy group at the C-5 position of the indole nucleus resulted in a short-lived and dose-dependent immediate antihypertensive and bradycardic response in anaesthetized spontaneously hypertensive rats (SHR). In addition, a carbomethoxy function at the beta-position of the side-chain of the tryptamines significantly increased the mean resting arterial blood pressure (MAP) in pithed rats and also produced contraction of the canine basilar artery in a dose-dependent fashion. Structure-activity relationships (SAR) suggest that the 5-alkoxy group is an important pharmacophore in the production of the antihypertensive effect and that the introduction of a hydroxymethylene group on the side-chain, instead of the carbomethoxy group, changed the receptor affinity profile.

Depression of fast axonal transport in axons demyelinated by intraneural injection of a neurotoxin from K. humboldtiana.

Tullidinol, a neurotoxin extracted from the Karwinskia humboldtiana fruit, dissolved in peanut oil was injected into the right sciatic nerve of adult cats. The contralateral sciatic nerve received an equivalent volume of peanut oil alone. The fast axonal transport of labeled ([3H]Leucine) protein was studied in sensory and motor axons of both sciatic nerves. The radioactive label was pressure injected either into the L7 dorsal root ganglion or the ventral region of the same spinal cord segment. Several days after the toxin injection, the cat limped and the Achilles tendon reflex was nearly absent in the right hind limb. The amount of transported label was decreased distal to the site of toxin injection. Proximal to this site, the transported material was damned. Sensory and motor axons showed similar changes. In addition, the toxin produced demyelination and axonal degeneration. Axonal transport and the structure of the axons were normal in the contralateral nerve. Both, Schwann cells and axons of the right sciatic nerve showed globular inclusions, presumably oil droplets containing the toxin. We conclude that Schwann cells and axons as well are tullidinol targets.

Efficacy of a putative GABA analog on synaptic transmission in the cat spinal cord.

4-Hydroxy-4-phenylcaproamide (HPhCA), at high doses or rates of IV injection depressed the ventral root reflexes elicited by nerve or dorsal root stimulation. The D (direct) and I (synaptic) ventral root waves and the antidromic (A) dorsal root wave evoked by intraspinal stimulation were also depressed. Similar effects were produced when HPhCA was applied topically on the cord dorsum. At 80 mg/kg and 8 mg/kg/min, the spinal reflexes and the I wave were facilitated for 4 to 6 h, but the D and A waves were depressed. Intracellular recordings from motoneurons showed that HPhCA injection produced: hyperpolarization that lasted several hours, short lasting (< 20 min) facilitation of both EPSPs and IPSPs as well as spike-like potentials (SLPs) that were triggered by EPSPs even though the neuron was hyperpolarized. SLPs may reach the threshold for full spikes. Our results suggest that the spinal depression results from hyperpolarization of motoneurons and the initial facilitation appears to be presynaptic. The late facilitation may be produced by SLPs. HPhCA does not appear to mimic the actions of GABA in primary afferents fibers and motoneurons.

Synthesis and 1H and 13C nuclear magnetic resonance of 16-methylene-17 alpha-hydroxypregna-1,4,9(11)-triene-3,20-dione.

A three-step synthesis of 16-methylene-17 alpha-hydroxypregna-1,4,9(11)- triene-3,20-dione, which has been previously obtained by microbial transformation, was achieved from 3 beta-hydroxy-16 alpha, 17-epoxy-16 beta-methyl-5 alpha-pregn-9(11)-en-20-one in an overall yield of 35%. All compounds involved in the process were characterized spectroscopically and their 13C NMR shielding effects are briefly discussed.

Antitumor effect and toxicity of two new active-site-directed irreversible ornithine decarboxylase and extrahepatic arginase inhibitors.

The irreversible ornithine decarboxylase and extrahepatic arginase inhibitors (+)-S-2-amino-5-iodoacetamidopentanoic acid (2-AIPA) and (+)-S-2-amino-6-iodoacetamidohexanoic acid (2-AIHA) were evaluated. The LD50 tests were made in rats and mice using both compounds. Rats and mice were treated with either 2-AIPA or 2-AIHA i.p. for a period of 180 days. The treated animals showed a decrease of total serum proteins and increased ALT and AST levels. CK was also modified but inversely related to dose. Protection tests were carried out using L5178Y mouse lymphosarcoma. The mean survival time for each treated group was calculated and the percentage T/C was determined. For 2-AIPA it was 170 and for 2-AIHA it was 210 at 15 mg/kg.

Coordination compounds derived from the interaction of streptomycin and cobalt, nickel, copper, and calcium salts characterized by 13C NMR and spectroscopic studies. Structure and bonding properties of the streptidine fraction.

The coordination compounds of streptomycin (St), Co2(St)Cl4.13H2O (2), Co2(St)(NO3)4.7H2O (3), Ni2(St)Cl4.14H2O (4), Ni2(St)(NO3)4.14H2O (5), Cu2(St)Cl4.6H2O (6), and Ca(St)Cl2.8H2O (7) have been synthesized by the reaction of streptomycin sulfate (1) with three equivalents of the corresponding inorganic salt. The compounds (2)-(7) were characterized by electronic spectroscopy (in the solid state and in solution) by conductivity measurements and by 13C NMR in solution. The reaction of streptomycin with CuCl2 in water hydrolyzed the molecule giving the copper complex of the streptidine fraction (Std), Cu(Std)Cl.H2O (8). This compound was characterized by the same techniques. Detailed x-ray diffraction and 13C NMR studies of streptidine sulfate (9) were carried out.