Manfred G. Reinecke

Ecdysteroids and other constituents from Sida spinosa L.

Two compounds (3 and 10) were isolated from the aerial parts of Sida spinosa L. Their structures have been established as glyceryl-1-eicosanoate and 20-hydroxy, 24-hydroxymethylecdysone by 1D and 2D-NMR techniques. In addition 12 known compounds (1, 2, 4-9 and 11-14) have been isolated and identified.

Thermolysis of thiophenedicarboxylic acid anhydrides as a route to five-membered hetarynes

Flow vacuum thermolysis (FVT) of the anhydrides of thiophene-2,3(5) and -3,4-dicarboxylic acid (6) and of thianaphthene-2,3-dicarboxylic acid (7) in the presence of thiophene, 1,3-cyclohexadiene, or benzene gave thianaphthene (Ma), presumably by aromatization of an intermediate Diels-Alder adduct of the diene traps and the aryne 2,3-didehydrothiophene (8). A similar rationale explains the formation of dibenzothiophene from 7 and thiophene, the four monomethylthianaphthenes 22-25 from 5 and cyclopentadiene, 5,6-dimethylthianaphthene (150 from 5 and 2,3-dimethylbutadiene, and a mixture of hydroxythianaphthenes ( 1 9 ) from 5 and furan. The latter reaction also produces a mixture of isomeric cyclopentenothiophenes (19) which probably arise by decarbnylation of 15d. An FVT reaction of 5 with propyne as the trap gave a mixture of allenyl(28) and propynylthiophenes 29 which probably arise by an ene reaction of the trap and the aryne 8. Decomposition of the anhydrides 5 and 6 in molten anthracene led only to Friedel-Crafts products such as thienylanthracenes 33 and quinones 34 from 5 and 39 and 40 from 6. The diene reactivity of thiophene 13a in the gas phase was demonstrated by the formation of naphthalene from its reaction with benzyne generated from the thermolysis of indanetrione and by the formation of indene from 13a plus cyclopentadiene. Possible, but improbable. interpretations of the FVT results without invoking a five-membered hetaryne intermediate are considered. Rationale An analysis2 of the abortive attempt^^,^ to generate five-mem bered hetarynes suggests that the difficulty arises because, compared to their six-membered analogues, potential five-membered hetaryne precursors are stabilized toward aryne formation and labilized toward nonaryne reactions. A prominent example of the first phenomenon is the relative stability of the o-bromolithium compounds 1 and 2 which respectively lose lithium bromide at

Alkaloids of the chinese herb guan-bai-fu (aconitum koreanum); guan-fu bases Y and A

Abstract A new alkaloid, guan-fu base Y,has been isolated from Aconitum koreanum (Levl.)Raipaics and shown to be 2-acetoxy-14-hydroxyhetisine ( 2 ) from its nmr (1H, 13C) and mass spectra. A completed assignment of mmr peaka was made with the help of NOE and 2-D experiments which also suggest a revised structure ( 3 ) for guan-fu baae A ( 4 ).

Cycloaddition reactions of 2,3-didehydrothiophene generated by flow vacuum thermolysis of thiophene-2,3-dicarboxylic anhydride

Abstract Flow vacuum thermolysis (FVT) of thiophene-2,3-dicarboxylic anhydride ( 2 ) in the presence of 2,3-dimethylbutadiene ( 6 ) gives, in addition to 5,6-dimethylthianaphthene ( 9 ). small quantities of a dihydrodimethylthianaphthene ( 12 ) and another dimethylthianaphthene ( 13 ) which is probably also formed by dehydrogenation of 12 with chloranil. The partial structures of these minor products are consistent with their being formed by a [2+2]-cycloaddition between 6 and an intermediate aryne, 2,3-didehydrothiophene ( 1 ), followed by a rearrangement of the resulting adduct 11 and dehydrogenation. FVT of 2 in the presence of 2,5- ( 17b ) or 3,4-dimethylthiophene ( 17c ) also gave a mixture of the dimethylthianaphthenes ( 18 22 , 23 ) which can be rationalized as arising by a [4+2]- and two [2+2]-cycloadditions of the aryne 1 to the thiophenes 17 with subsequent desulfurization. The lack of equilibration of the products 18 , 22 and 23 , was demonstrated and their origin as a function of the structure and reactivity of the aryne 1 discussed.

Pharmacological Survey of Medicinal Plants for Activity at Dopamine Receptor Subtypes. II. Screen for Binding Activity at the D1 and D2 Dopamine Receptor Subtypes

Aqueous, organic and alcoholic extracts of 163 Bolivian, Chinese and Pakistani medicinal plants were evaluated for their ability to inhibit the binding of radioligands selective for the D1 and D2 dopamine receptor subtypes expressed in Sf9 cells. Based upon the results of the initial screen, 25 extracts were selected for further evaluation. Concentrationresponse competitive radioligand binding studies were performed to obtain IC 50 values for the inhibition of the binding at D1 or D2 receptors by the selected extracts. The D1:D2 receptor ratio of IC 50 values for the extracts ranged from approximately two-fold selective for the D1 receptor to threefold selective for the D2 receptor. D1 and D2 dopamine receptors are known to be linked to the activation and inhibition of adenylyl cyclase activity, respectively. Therefore, the selected extracts were tested for the ability to either a) stimulate adenylyl cyclase activity using stably transfected HEK 293 cells expressing human D1 receptors (hD1-HEK) or b) inhibit forskolin-dependent stimulation of adenylyl cyclase activity in stably transfected HEK 293 cells expressing rat D2 dopamine receptors (rD2-HEK). Two extracts were found to stimulate adenylyl cyclase activity in hD1-HEK cells. However, similar results were observed when untransfected HEK cells were used, suggesting that the ability of these two extracts to increase cAMP levels in hD1-HEK cells was not mediated through a D1-like dopamine receptor. While the majority of extracts did not have an effect on forskolin-dependent stimulation in rD2-HEK cells, six extracts were capable of inhibiting adenylyl cyclase activity in these cells. For five of these extracts, the inhibitory effect appeared to be dependent upon the expression of D2 receptors because no inhibitory effect was observed when untransfected HEK 293 cells were used. In summary, the results of this preliminary radioligand binding and functional activity screen of extracts from medicinal plants for pharmacologic activity at D1 and D2 dopamine receptors indicated that the majority of components capable of binding to the D1 and D2 dopamine receptor subtypes appeared to be essentially nonselective. While none of the selected extracts were found to have agonist activity at D1 receptors, several of the extracts exhibited inverse agonist activity at D1 dopamine receptors. Five of the extracts appeared to be agonists at D2 dopamine receptors. Therefore, several classes of extracts were identified which appeared to contained unique combinations of the following pharmacologic properties: D1 dopamine receptor antagonist, D2 dopamine receptor antagonist, D1 receptor inverse agonists and D2 receptor agonists. In addition, two of the extracts tested appeared to modulate adenylyl cyclase activity, but this activity did not appear to be mediated through activation of a dopamine receptor subtype.

Inhibition of Synaptosomal Neurotransmitter Uptake by Hallucinogens

The effect of 13 hallucinogens on the uptake of serotonin and norepinephrine into hippocampal synaptosomes and of serotonin and dopamine into caudate synaptosomes was found to be inhibitory, except for lysergic acid diethylamide and 2‐bromolysergic acid diethylamide, which were inactive. The indoleal‐kylamines were generally more potent than the phenylethylamines. The reported inhibition of uptake of serotonin by 5‐methoxy‐N,N‐dimethyltryptamine and lysergic acid diethylamide into whole brain synaptosomes was not reproducible at concentrations 102 to 104 times higher than those stated in the literature.

3,4-Didehydropyridine plus cyclopentadiene: [2+2] or [4+2]-cycloaddition ?

Abstract 3, 4-Didehydropyridine ( 2 ) generated from two precursors ( 6 and 7 ) of the diazonium carboxylate 5 reacts with cyclopentadiene to give the [ 4+2 ] -cyclo-addition product 3 rather than the [2+2]-adduct 4 proposed in the literature. The structure of 3 was supported by complete proton and carbon NMR assignments made with the aid of decoupling and 2D experiments.

Heterotriptycenes from a five-membered heterocyclic diazonium carboxylate

Abstract Heterotriptycenes ( 4 ) are formed when the benzo [b]thiophene diazonium carboxylate ( 1 ) is decomposed in the presence of anthracenes ( 2 ).

Pharmacological Survey of Medicinal Plants for Activity at Ligand-Gated Ion Channels: Selective Interaction with 5-HT3 Receptors

The ligand-gated anion-selective ion channels are part of a superfamily of ligand-gated ion channels (LGICs) that are responsible for a majority of inhibitory signaling in the central nervous system and are the targets of numerous therapeutics. Aqueous, organic and alcoholic extracts of 47 Chinese, Bolivian and Pakistani medicinal plants were evaluated for the ability to modulate the activity of GABAA receptors. Extracts were initially screened for their ability to modulate activity of α1β2γ2 GABAA receptors expressed in HEK 293 cells. Based on the initial screen, two extracts derived from members of the Asteraceae family, Xanthium spinosum and Senecio mathewsii, were chosen for more detailed analysis. Xanthium spinosum inhibited GABAA receptor function, with an IC50 of 50 ± 10 µg/ml, while Senecio mathewsii inhibited GABAA receptor activity with an IC50 of 35 ± 3.0 µg/ml. To assess the selectivity of interaction, these extracts were also tested on two other members of the LGIC superfamily a) glycine receptors, a distinct inhibitory neurotransmitter receptor and b) 5-HT3A receptors, a cation-selective receptor. At a concentration of Xanthium spinosum that blocked 70% of GABA-activated current, only 15% of glycine-gated current, recorded from recombinant α1 glycine receptors, was blocked, suggesting a lower affinity of Xanthium spinosum for glycine receptors. Senecio mathewsii had larger inhibitory effects on glycine receptors than Xanthium spinosum, although the apparent affinity still was estimated to be three-fold lower than that seen for GABAA receptors. Xanthium spinosum and Senecio mathewsii also inhibited 5-HT3A receptor functions. Notably, the IC50 of both extracts was seven to ten-fold lower than that observed for GABAA receptors. Thus, the rank order of potency for organic extracts from both Xanthium spinosum and Senecio mathewsii was 5-HT3A receptors > GABAA receptors > glycine receptors. Therefore, these extracts may be a source of novel compounds that may serve as lead molecules for the development of novel 5-HT3 receptor antagonists.

1,3-Cycloaddition of benzyne to thiophens

Benzyne, generated from diphenyliodonium-2-carboxylate, reacts with varous thiophens by addition to the sulphur and β-carbon to give, after loss of an acetylene moiety, benzo[b]thiophens in low but reproducible yields.