Quality and quantity of morphinan alkaloids detectable in interspecific hybrids of the genus papaver*

Viable hybrids were artificially produced between PAPAVER BRACTEATUM rich in thebaine on the one side and PAPAVER SOMNIFERUM, PAPAVER ORIENTALE and PAPAVER PSEUDO-ORIENTALE on the other side. Each of them is characterized by morphological and some physiological features as well as by its chromosome number. Biochemical analysis confirmed that P. SOMNIFERUM-P. BRACTEATUM hybrids contain very high morphine concentrations if the biosynthetic activity of the first parent is not to low. Also other conditions favouring the morphine yield of this hybrid could be elucidated. - Oripavine is the main alkaloid in P. ORIENTALE-P. BRACTEATUM hybrids. However, its concentration remains low. This is probably due to the limited oripavine biosynthesis in P. ORIENTALE plants used for cross experiments. - P. BRACTEATUM-P. PSEUDO-ORIENTALE hybrids contain thebaine only in trace amounts. These small quantities are characteristic of the P. PSEUDO-ORIENTALE parents. Interspecific hybridizations corresponding to a "genetic feeding experiment" generally result in increased concentrations of desired morphinan alkaloids. However, their effectiveness remarkably depends on the following fact: Low alkaloid levels may frequently be the expression of a reparable shortage, but they can also be caused by a strict regulation snowing dominant inheritance.     

HPLC investigation of the inheritance of major opium alkaloids1.

Inheritance of five major alkaloids, morphine, codeine, thebaine, narcotine and papaverine has been studied in interspecific cross, PAPAVER SOMNIFERUM x P. SERIGERUM. Heterotic increase in codeine and thebaine was found in different F (1) plants while in some F (2) plants the content of all these alkaloids except that of codeine exceeded the content of these alkaloids found in parental and F (1) generations. The absence of narcotine was generally dominant over its presence.     

Infraspecific variation and alkaloids of papaver species

Many species of PAPAVER exist as chemical races and, in order to illustrate this fact, examples have been chosen from the sections Miltantha and Oxytona. Future work on the alkaloids of PAPAVER species, including the possibility of novel compounds, aspects of biosynthesis and plant cell culture, are briefly discussed.     

Comparison of chemical and botanical studies of Turkish papaver belonging to the section pilosa

The alkaloidal contents of the Turkish PAPAVER belonging to the section PILOSA have been studied by high performance liquid chromatography. According to the results obtained, the section PILOSA should be divided into two subsections; the first being characterised by the presence of the alkaloids amurine, glaucine and roemerine and the second by protopine and rhoeadine. These conclusions were confirmed by the botanical studies.     

Alkaloids from Papaver cylindricum.

The major alkaloids obtained from PAPAVER CYLINDRICUM C ULLEN were oripavine, narcotine, thebaine and rhoeadine. Floripavidine, papaverine, salutaridine, armepavine, N-methylasimilobine, scoulerine and cheilanthifoline were obtained as minor alkaloids. There have been no previous reports of alkaloids from P. CYLINDRICUM.     

Uber den Alkaloidgehalt des Ziermohns.

17 varieties of ornamental poppy - cultivated in West Germany - (cultivar. of PAPAVER ORIENTALE L., P. PSEUDO-ORIENTALE (Fedde) Medw. and P. BRACTEATUM (Lindl.) were examined for their alkaloid composition and for their content in the ripe capsules. Contents between 0.2 and 1.2 per cent were found, depending on the variety with isothebaine and thebaine as the main alkaloids. One group contains only isothebaine, another one thebaine besides isothebaine, and in a relatively small group thebaine proved to be the main alkaloid. As shown in the discussion, there is no reasonable evidence to forbid cultivating ornamental poppy.     

Morphinan Alkaloid Production by Tissues Differentiated from Cultured Cells of Papaver somniferum (1).

From cultured cells of PAPAVER SOMNIFERUM L., green buds and shoots were formed at a high frequency under illumination at low temperatures, 16-18 degrees C. Differentiation was induced from meristemoids which contained large amounts of lipids. The differentiated tissues completely recovered the potential to biosynthesize morphinan alkaloids that was lost in the undifferentiated cells, i.e. calli. Moreover, it was confirmed by enzyme immunoassay (EIA) for opiate that the tissues, which differentiated only a tracheary element, produced morphinan alkaloids, especially codeine as a main component.     

Salutaridine N-Oxide from the Capsules of Papaver bracteatum

A novel compound, salutaridine N-oxide ( 1) has been isolated from PAPAVER BRACTEATUM Lindl (Papaveraceae) in which the major alkaloids were salutaridine and thebaine. Semisynthetic 1 was prepared for structure confirmation. Other components of the alkaloidal fraction were isothebaine, oripavine, neopine, and thebaine N-oxide.     

Alkaloids from Papaver triniifolium of Turkish Origin1

The major alkaloids of PAPAVER TRINIIFOLIUM collected in two different parts of Anatolia have proved to be of the aporphine, morphinane and rhoeadine types. The two collections possessed different major alkaloids and the existence of chemical strains is indicated. In addition to the aporphine-(floripavidine), the morphinandienone-(amurine and salutaridine), benzylisoquinoline-(papaverine), proaporphine-(mecambrine) and tetrahydroprotoberberine-(sinactine, scoulerine and cheilanthifoline) type alkaloids have been isolated as minor alkaloids.     

Alkaloids from Turkish samples of Papaver orientale and P. pseudo-orientale

The alkaloids obtained from the capsules of five different collections of wild P. ORIENTALE and sixteen different collections of wild P. PSEUDO-ORIENTALE have been investigated and the chromosome numbers of some of the samples determined. Oripavine was the major alkaloid obtained from four of the P. ORIENTALE collections, two of which had a diploid chromosome number of 28. These four samples contained isothebaine and alpinigenine as minor alkaloids whereas two contained mecambridine and orientalidine and the other two contained thebaine and salutaridine. The remaining sample of P. ORIENTALE contained mecambridine as the major alkaloid and also some orientalidine. Thirteen of the sixteen samples of P. PSEUDO-ORIENTALE contained isothebaine, mecambridine and orientalidine as their major alkaloids with thebaine and salutaridine as minor alkaloids. Alpinigenine was detected in three samples. The diploid chromosome number of four of the thirteen samples was determined as 42. Two samples of P. PSEUDO-ORIENTALE contained salutaridine and thebaine as major alkaloids and had a diploid chromosome number of 14 whereas the remaining sample yielded salutaridine as the major alkaloid with isothebaine, mecambridine and orientalidine as minor alkaloids and a diploid chromosome number of 28.     

Somatic embryogenesis and rhizogenesis of tissue cultures of two genotypes of Papaver somniferum: relationships to alkaloids production

PAPAVER SOMNIFERUM L. tissue cultures, issued from various explants (cotyledons, hypocotyls, roots) derived from plantlets belonging to two genotypes, were established on LS solid medium containing growth regulators (NAA, Kin) in various combinations. Hypocotyls and roots were found to be interesting explants to obtain cellular development. Many roots developed on calli growing on a medium containing NAA (1 mg/l) + Kin (0.1 mg/l) for the PS genotype while somatic proembryos redifferentiated on calli issued from PS 1639 genotype. The same growth substance combination was the most favourable for the production of morphinan alkaloids and papaverine: up to 10 x 10 (-3)% DW in roots redifferentiated from PS calluses.     

Alkaloid profiling of crude and processed Veratrum nigrum L. through simultaneous determination of ten steroidal alkaloids by HPLC-ELSD

Veratrum nigrum L., a traditional Chinese herb, has been used for treatment of hypertension, blood-stroke, excessive phlegm, epilepsy, etc. Steroidal alkaloids were well-known as both bioactive and toxic constituents of Veratrum species, the toxicity of which the traditional processing procedure can reduce. To reveal the mechanism of processing V. nigrum L., a high performance liquid chromatography (HPLC) with evaporative light scattering detector (ELSD) method was developed for the simultaneous determination of ten steroidal alkaloids in crude and processed V. nigrum L., comparison with ultrasound extract of crude V. nigrum L. With a Venusil XBP-C(18) analytical column, the analytes were separated efficiently using the mobile phase consisted of (A) 0.03% aqueous triethylamine (TEA) and (B) acetonitrile in a gradient program. The parameters for ELSD were set: S.C. (Spray Chamber)=35 degrees C, D.T. (Drift Tube)=70 degrees C, GAS=50 psi. All calibration curves showed good linear regression (gamma>or=0.9990) within the tested range. Additionally, reproducibility for the quantification of ten alkaloids in V. nigrum L. with intra- and inter-day variations of less than 5.0% was observed. The obtained alkaloid profiles performed by this newly established method, provided valuable information for the differentiation of crude and processed V. nigrum L. and for the explanation of the different toxicity.     

Morphological Characterization of the Genus Datura: Section Stramonium

Abstract

To achieve a systematic identification and differentiation of the species belonging to the various sections of this genus, the surface characteristics of species of section Stramonium (D. stramonium L., D. inermis Jacq., D. tatula L., D. stramonium L. var. godronii Danert, D. ferox L., D. quercifolia H.B.K.) have been examined by Scanning Electron Microscope (SEM).

Cell shape and size, number and disposition of both protective and glandular hairs, stomatal, vein-islet and veinlet termination numbers allow one to characterize the different samples examined.     

Further studies on the synthesis of 7,17-seco norditerpenoid alkaloids

Following the report on the synthesis of the 7,17-seco compounds [Wang, F.P., Yang, J.S., Chen, Q.H., Yu, L. and Li, B.G. (2000), Chem. Pharm. Bull. 48, 1912-1916], further studies on the reaction optimization for cleavage of the C(7),C(17) bond led to the 7,17-seco norditerpenoid alkaloids (e.g. 4, 9) in nearly 90% yield.     

New Sesquiterpenoids from the Rhizomes of <i>Petasites japonicus</i> M<small>AXIM</small>. and the Roots of <i>Ligularia dentata</i> H<small>ARA</small>

Over the past twenty years, our research group has been involved in the phytochemical study of terpenoids from Compositae plants. From seven species, namely, Erigeron annuus (L.) PERS., Erigeron philadelphicus L., Erigeron sumatrensis RETZ., Ligularia dentata HARA, Ligularia stenocephala MATSUM. et KOIDZ., Petasites japonicus MAXIM., and Tussilago farfara L., we isolated 83 new compounds. In this review, structural features of 19 eremophilane-type sesquiterpenoids from rhizomes of P. japonicus and 9 bisabolane-type sesquiterpenoids from roots of L. dentata are discussed.     

Alkaloids in ergot found on different Gramineae in The Netherlands

The alkaloid content and the composition of the alkaloid complex of thirteen samples of ergot sclerotia from different gramineous host species collected in The Netherlands were investigated. Two samples collected in France were also examined. Ergot ofGlyceria fluitans (L.) R.Br. did not contain alkaloids. The total alkaloid content of ergot found on the other wild grasses was more than 0.2%. The ratio between the contents of water soluble and water insoluble alkaloids of the investigated ergot sclerotia varies between 1∶10 and 1∶20. The composition of the alkaloid complex in the sclerotia was studied by quantitative thin-layer chromatography. The sclerotia could be grouped into three main categories:

sclerotia ofLolium perenne L.,Festuca arundinacea Schreb. andArrhenatherum elatius (L.) P.B. ex J. et C. Presl, containing predominantly ergocornine, α- and β-ergokryptine and ergosine;

sclerotia ofDactylis glomerata L.,Phalaris arundinacea L.,Alopecurus geniculatus L. andHolcus mollis L., containing predominantly ergosine, ergocristine and ergotamine;

sclerotia ofMolinia caerulea (L.) Moench, containing predominantly ergocristine, ergosine and ergqmetrine.

A great similarity was found between the composition of the alkaloid complex in ergot ofLolium perenne L. from different locations and also in ergot ofMolinia caerulea (L.) Moench from different locations. This similarity was less in ergot ofDactylis glomerata L. collected from different locations.     

红白忍冬的染色体及核型分析

目的对红白忍冬[Lonicera japonica Thunb.var.chinensis(Wats.)Bak.]的染色体数目和核型进行研究。方法采用常规制片方法,经显微摄影后对染色体进行分析。结果红白忍冬的体细胞染色体数目2n=18,核型公式为K(2n)=2x=18=2m+12sm(2SAT)+4st(4SAT),染色体相对长度组成为2n=18=4L+2M2+10M1+2S,染色体总长为31.269μm,长臂总长为21.963μm,核型不对称系数(AS.K)为70.24%,属于"3B"型。结论红白忍冬体细胞染色体的数目、核型等清晰准确。     

Diterpenoid alkaloids from the aerial parts of Aconitum anthora L

Isolation and identification of six diterpenoid alkaloids, from Aconitum anthora L. are described. All proton detected 2D NMR techniques have been used for unambiguous 1H and 13C chemical shift assignments of guan-fu-base-Y (6). This is the first investigation of the diterpenoid alkaloids of this plant species.     

Alkaloid Constituents of Sida acuta, S. humilis, S. rhombifolia and S. spinosa*.

Three types of alkaloidal constituents, viz., beta-phenethylamines, quinazolines and carboxylated tryptamines, in addition to choline and betaine have been isolated from SIDA ACUTA B URM., S. HUMILIS W ILLD., S. RHOMBIFOLIA L., and S. SPINOSA L. and characterized by their physical and spectral properties, and by chemical transformations. The qualitative and quantitative variations in the alkaloidal constituents of roots and aerial portions at different stages of growth were also noted. Elaboration of the quinazoline alkaloids seems to be a characteristic feature of this genus. The favourable combination of sympathomimetic amines and vasicinone in these species would account for their major therapeutic uses in the Indian system of medicine.     

Application of PBPK modeling in support of the derivation of toxicity reference values for 1,1,1-trichloroethane

PBPK modeling has been increasingly applied in chemical risk assessment for dose, route, and species extrapolation. The use of PBPK modeling was explored in deriving toxicity reference values for 1,1,1-trichloroethane (1,1,1-TCE). This effort involved a 5-step process: (i) reconstruction of several published PBPK models for 1,1,1-TCE in the rat and human; (ii) selection of appropriate pharmacokinetic datasets for model comparison; (iii) determination of the most suitable PBPK model for supporting reference value derivation; (iv) PBPK model simulation of two critical studies to estimate internal dose metrics; and (v) calculation of internal dose metrics for human exposure scenarios for reference value derivation. The published model by Reitz et al. [Reitz, R.H., McDougal, J.N., Himmelstein, M.W., Nolan, R.J., Schumann, A.M., 1988. Physiologically based pharmacokinetic modeling with methylchloroform: implications for interspecies, high dose/low dose, and dose route extrapolations. Toxicol. Appl. Pharmacol. 95, 185-199] was judged the most suitable. This model has liver, fat, and rapidly and slowly perfused compartments, contains a saturable process for 1,1,1-TCE hepatic metabolism, and accommodates multiple exposure pathways in three species. Data from a human volunteer study involving acute inhalation exposure [Mackay, C.J., Campbell, L., Samuel, A.M., Alderman, K.J., Idzikowski, C., Wilson, H.K., Gompertz, D., 1987. Behavioral changes during exposure to 1,1,1-trichloroethane: time-course and relationship to blood solvent levels. Am. J. Ind. Med. 11, 223-239] and a chronic rat inhalation study [Quast, J.F., Calhoun, L.L., Frauson, L.E., 1988. 1,1,1-Trichloroethane formulation: a chronic inhalation toxicity and oncogenicity study in Fischer 344 rats and B6C3F1 mice. Fundam. Appl. Toxicol. 11, 611-625] were selected to simulate appropriate internal dosimetry data from which to derive reference value points of departure. Duration, route, and species extrapolations were performed based on internal dose metrics.