A. Nabiev, and V. U. KhuzhaevA series of new convolvine derivatives based on the alkaloid from Convolvulus subhirsutus and C. pseudocanthabrica were synthesized using alkylhalides and aliphatic and aromatic acid chlorides. Results of biological tests showed that convolvine and its derivatives exhibited pronounced antihypoxic, immunomodulating, and anti-inflammatory activity.The aerial parts of Convolvulus subhirsutus and C. pseudocanthabrica growing in Uzbekistan [1] have previously yielded 10 alkaloids [2-7] that were tropane derivatives, the principal ones being convolvine and convolamine with a content of 45-50% of the total alkaloids. A quantitative determination found that the content of the alkaloid mixture in the aerial part was 0.6%; in the roots, 1.6% of the dry plant weight.The convolvine content in C. subhirsutus and C. pseudocanthabrica reaches 0.3% in the aerial part; 0.7%, in roots. As a result of the availability of convolvine, a series of its derivatives were prepared. Their pharmacological properties were studied in a search for compounds with valuable pharmacological activity. For this, convolvine (1) was reacted with alkyl halides (methyliodide, hexylbromide, amylbromide, nonylbromide, benzylchloride) to produce the corresponding derivatives N-methylconvolvine hydroiodide (2), N-amylconvolvine hydrobromide (3), N-hexylconvolvine hydrobromide (4), N-nonylconvolvine hydrobromide (5), and N-benzylconvolvine (6) according to the scheme:Convolvine was also reacted with aliphatic and aromatic acid chlorides to produce N-benzoylconvolvine (7), N-chloroacetylconvolvine (8), and N-4c-nitrobenzoylconvolvine (9), reduction of 9 produced N-4c-aminobenzoylconvolvine (10), and N-naphthoylconvolvine (11):

547.944/945 N. D. Abdullaev, and V. U. KhuzhaevCrambe orientalis L. (C. amabilis Butk. et Majlun) belongs to the family Cruciferae, is a perennial herbaceous plant of height 30-80 cm, and grows wild in the Caucasus (eastern and southern foothills) and Central Asia (Tian-Shan, west) [1, 2] on dry stony and pebbly slopes in the lower and middle mountain belts and as a weed in plantings. The chemistry of this species of Crambe is little studied. Only the presence in the plant of phospholipids, vitamin C, trace elements [3], and fatty oil [4] has been reported. Seeds and fruit are rich (up to 25-35%) in fatty oil, which was shown to contain myristic, palmitic, stearic, oleic, arachic, arachidonic, erucic, linoleic, linolenic, palmitoleic, lignocerinic, eicosanoic, and eicosadienoic acids [4]. The fatty oil is suitable as food. Leaves and runners are used in the Caucasus as an antiscorbutic agent and in food as asparagus [5]. C. orientalis was introduced to Samarkand Oblast. The harvest of greens reaches 375-425 Cwt/ha [6]. It was tested as a promising feed plant [7,8].Alkaloids from this plant species were not previously studied. Plants of the family Cruciferae typically contain S-containing alkaloids [9]. The alkaloid composition of C. orientalis has not been reported. Only brief information on the alkaloid composition of C. kotschyana is available [10].We studied the alkaloids and other low-molecular-weight metabolites of C. orientalis collected in the vicinity of Gazalkent, Tashkent Oblast. Quantitative determination of total alkaloids from roots and the aerial part collected at the end of vegetation (October 2010) found contents of 0.064 and 0.06%, respectively, of the air-dried raw material weight. Total alkaloids were extracted from the aerial part of the plant collected from this site.The mixture of bases were extracted and isolated from the aerial part of the plant (11 kg) by EtOH (85%, 8u). The combined and condensed alcohol extracts were worked up with H 2 SO 4 solution (5%, 6u). The acidic extracts were washed with benzene and made basic with NH 4 OH solution (conc.) until the pH was 10-11. The alkaloids were extracted with CHCl 3 (6u). The CHCl 3 extracts were dried over anhydrous Na 2 SO 4 . The solvent was distilled off to afford total alkaloids (7.0 g). Analogously the mixture of bases (4.0 g) was obtained from roots (6 kg).The CHCl 3 total alkaloids from the aerial part and roots that were obtained from this process were chromatographed over a column of silica gel with elution by hydrocarbons:CHCl 3 (1:1, system 1) to produce five fractions with similar R f values. Rechromatography of these produced homogeneous fractions and isolated two known oily alkaloids with R f 0.5 (goitrin) and 0.3 (goitridin) (TLC, silica gel, system 1) that were isolated previously from C. kotschyana [11].The mother liquor from the CHCl 3 total was analyzed by GC-MS. Table 1 presents the results. The principal component of the mother liquor was buten-1-isothiocyanate (allyl isothiocyanate, allyl mustard oil). The hydrocarbo...

The minor base convolinine was synthesized. The activity of alkaloids from plants of the genus Convolvulus and their derivatives against HeLa and Hep cancer cell cultures and primary fibroblast culture was studied. It was found that the alkaloid convolvine and its derivatives exhibited cytotoxic activity. The alkaloids N-benzylconvolvine (4) and N-chloroacetylconvolvine (5) at concentrations of 10 Pg/mL exhibited the greatest activity against HeLa and Hep cancer cell cultures. The percent suppression of HeLa cervical carcinoma cells by alkaloid 4 was 35%; of Hep laryngeal cancer cells, 81.6%.A multitude of antitumor drugs are currently produced from alkaloids of plant origin. These include vinblastine, vincristine, and vinorelbine from Vinca rosea L.; docetaxel, from Taxus baccata; etoposide, from Podophyllum peltatum L., etc. The antitumor activity of the alkaloids and their derivatives is due to their influence mainly on cellular metabolism during the M-phase of the cell cycle (mitosis) through binding to tubulin molecules in microtubules. They prevent polymerization of this protein, retard formation of the division spindle (assembly of microtubules), and stop mitosis at the metaphase stage [1].The goal of the present work was to find compounds with cytotoxic activity among alkaloids of the genus Convolvulus (Convolvulaceae) and their derivatives. These alkaloids belong to the tropane class and were isolated from plants of the genus Convolvulus (C. subhirsutus, C. krauseanus, C. pseudocanthabrica) in the Central Asian flora [2].The three alkaloids convolvine (1), convolidine (2), and convolinine (3) were isolated from plants of the genus Convolvulus [3,4]. N-Benzylconvolvine (4) and N-chloroacetylconvolvine (5) are synthetic analogs of convolvine [5].Because convolinine (3) is a minor alkaloid of C. subhirsutus [6], it was synthesized from convolvine in order to study its cytotoxic properties. Its content in C. subhirsutus is 0.25-0.35% of the air-dried raw material mass [3]. The reaction of 1 and ethylenechlorohydrin (6) in the presence of Et 3 N produced 3, which was identical to the natural alkaloid convolinine according to spectral properties (see Experimental).

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