The reaction of harmine with phenacyl bromides or ethyl bromoacetate gives quaternized harmine derivatives. The cyclization of the phenacylharminium salts yields the corresponding 2-aryl-11H-indolizino[8,7-b]indoles. Vilsmaier-Haack formylation of 11H-indolizino[8,7-b] indoles leads to the corresponding 3,10-bisformyl derivatives. The acylation proceeds selectively at C( 3) to give 3-acetyl-2-aryl-11H-indolizino[8,7-b]indole.

The data on natural sources of betulin and methods of its extraction are systematized in the review. Transformations of betulin and its available derivatives are considered. The data on the biological activity of betulin, its natural and synthetic analogs are presented. The promising character of the compounds based on betulin for creation of antiviral and antitumour agents.

The composition of extractives from the top part of Halenia corniculata were investigated. Two individual compounds were extracted and characterized.

Total DNA was extracted from the leaves of a F1 hybrid and its parents, Papaver bracteatum Lindle and P. pseudo-orientale Medw. Analysis of random-amplified polymorphic DNA (RAPD) using ten arbitrary oligonucleotide 10-mers, showed that F1 hybrid was confirmed to be genetically intermediate of both parental plants compared with the genetic distance between F1 hybrid and individual parents. Furthermore, the comparison of the band patterns between a F1 hybrid, P. bracteatum and P. pseudo-orientale clearly showed that part of the bands of both parents were induced into a F1 hybrid. The content of thebaine was determined by HPLC and ELISA used anti-thebaine monoclonal antibody.

New derivatives of 6,14-endo-etheno-thebaine were studied with respect to their analgesic potency. The compounds contain a C7,8-positioned aromatic fragment with additional hydroxyl, thioalkyl, or acetamide moiety, as well as a thiolane dioxide fragment. New compounds were obtained, showing neither respiratory depression nor bronchospasms initiation. Their therapeutic indices were found to range from 100 to 666 units. The new tetrahydrothebaine derivatives represent morphine agonists, as concluded by the co-ordinated locomotor activity in laboratory animals. The described set of compounds is of practical importance in terms of successful searches for new selective receptor ligands. One of the most active compounds was analyzed by X-ray investigation.

Polycyclic structural analogues of natural quinones (dienonaphtha-, anthra- and naphthacenequinones) have been synthesized by cycloaddition reactions of 2-isopropenyl-2-thiolene-1,1-dioxide with quinones. The cycloadditon reaction of quinones with oxasoles is a route to isoquinolinoquinones or pyrrolonaphthoquinones. Anthra- and- naphthoquinones containing a terpenoid fragment have been synthesized by retro-decomposition of cycloadditon products of levopimaric acid with quinones.

Rat liver and kidney were investigated for the presence of sigma (σ) receptor subtypes by radioligand binding with three highly selective σ probes and by photoaffinity labeling using [H]azido-di-o-tolyguanidine ([3H]azido-DTG). [3(+)- Pentazocine, a highly selective σ1 probe, bound to sites in liver membranes with Kd = 7.5 nM and Bmax = 2929 fmol/mg protein. [3H](+)-Pentazocine binding sites in kidney had Kd = 23.3 nM and Bmax = 229fmol/mg protein. [3H1,3- Di-o-tolylguanidine ([3H]DTG) and [3H](+)-3-(3-hydroxyphenyl-N-(1-propyl)piperidine ([3H](+)-3-PPP) label both σ1 and σ2 receptors. Parameters for [3H]DTG in the liver were Kd = 17.9 nM and Bmax - 11 895 fmol.mg protein. Similar parameters were observed for [3H](+)-3-PPP, Kd = 51.9 nM and Bmax = 11 070 fmol/mg protein. [3H]DTG bound to rat kidney with Kd = 45.8 nM and Bmax = 1190 fmol/mg protein. The observation that either [3H]DTG or [3H](+)-3-PPP labeled a higher number of sites relative to [3H](+)-pentazocine suggested that liver and kidney contain both subtypes of σ receptor. This was confirmed by competition studies vs. [3H](+)-pentazocine and [3H]DTG (in the presence of dextrallorphan to mask σ1 sites). In both tissues, [3H](+)-pentazocine labeled sites with high affinity for haloperidol and enantioselectivity for (+)-benzomorphans over (−)-benzomorphans. [3H]DTG + dextrallorphan labeled sites in both tissues which also high affinity for haloperidol, but which had the characteristic σ2 property of low affinity for (+)-benzomorphans and enantioselectivity for (−)-benzomorphans over the corresponding (+)-isomer. Similar results were obtained with [3H](+)-3-PPP + dextrallorphan. Several novel aryl diamines, such as 1S, 2R-cis-N-[2-(3,4-dichlorophenylethyl]-N-methyl-2-(1-pyrrolidinyl)cyclohexylamine BD737) and N-2- (3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (BD1008), bound to both sites with high affinity. Photoaffinity labeling with 10 nM [3H]azido-DTG resulted in specific labeling of polypeptides of 25 kDa and 21.5 kDa and 21.5 kDa. Dextrallorphan (100 nM or 500 nM) completely blocked labeling of the 25 kDa polypeptide, but had no effect on labeling of the lower molecular weight protein. (+)-10,11-Dihydro-5-methyl-5H-dibenzol[a,d]cyclohepten-5,10-imine((+)_-MK-801) had no effect on labeling of either polypeptide. These data are consistent with the notion that the 25 kDa and 21.5 proteins represent σ2 and σ2 receptors, respectively. Thus, rat liver and kidney contain high densities of σ1 and σ2 receptors, with σ2 sites comprising 75–80% of the total σ population. The high density of σ receptor subtypes may indicate important functions in hepatic and renal tissues.

The reaction of 2-thiolen-4-on-1,1-dioxide 1a with thebaine in benzene was demonstrated to proceed regio- and stereoselectively and to produce 6,14-endo-etheno-7,8α (2',3'-thiolane-,4'-on-1',1'-dioxido)-tetrahydrothebaine 3, the conversion of the latter into epimeric compound 9 being aided by sodium methylate. The cleavage of the thiolane ring in 3 resulted in 5,14-endo-ethane thebaine derivative; thermolysis was carried out to lead to tetrahydro-5H-furobenzazocine derivative. The formations of the ion complexes of thebaine and ketone 1a were observed in the solutions of methanol and acetonitrile.

AbstractReaction between thebaine (I) and the dioxide (II) in boiling benzene yields the compounds (III) and (IV).