For the search for a domestic natural source of allylpolyalkoxybenzenes and development of an effective process for their isolation, CO 2 extracts of several varieties of parsley, dill, celery, caraway, and nutmeg were analyzed systematically for the first time by GC/MS and GLC techniques. The varieties with high contents of myristicin, elemicin, allyltetramethoxy benzene, apiol, and dillapiol were identified. The conditions of CO 2 extraction for obtaining concentrates with minimum contents of the distillation residues were selected. Using high performance fractional distillation, polyalkoxyallylbenzenes with 98-99% purity were isolated from the concentrates on a pilot unit. By isomerization of some allylbenzenes followed by ozonolysis under specially selected conditions, apiol and dillapiolaldehydes were obtained in 75-80% yields.This communication opens a series of works dealing with the chemistry of polyalkoxybenzenes, which we use as the basis for the development of analogs of natural food components and natural antimitotic antitumor agents. The isolation of valuable components from plant sources for fine organic chemistry and pharmaceutics is especially topical provided that this process is economically and environmentally more efficient than the synthetic manu facture. For the development of such processes, it is necessary, first of all, to find plants with high contents of the required metabolites. Second, it is necessary to use raw materials produced on a large scale; in this respect agricultural crops with well developed growing and har vesting processes are cheaper than the wild growing plants. Third, the existing industrial processes for plant raw ma terial processing should be employed.The efficient and environmentally safe extraction with both supercritical and liquid CO 2 (in particular, ultra sound assisted) has long been used in Russia for the in dustrial manufacture of spices: allspice, cinnamon, pep per, dill, nutmeg, caraway, anise, parsley, celery, mint, and so on. 1 These extracts are widely used as food addi tives, dressings, and antioxidants, especially in the fish canning industry. In the world practice CO 2 extraction of plants has been studied in recent years 2 in relation to the search for natural antioxidants 3 and the limitations on the use of conventional solvents in food and pharmaceutical industries.Analysis of the recent publications 4 and databases* on the compositions and biological properties of more than 30000 plants showed that umbelliferous crops (parsley, celery, dill, caraway, etc.) contain considerable amounts of diverse allylpolyalkoxybenzenes 1-5. R 1 = OMe, R 2 = H (apiol, 1), R = H (elemicin, 4), R 1 = H, R 2 = OMe (dillapiol, 2), OMe (allyltetra R 1 = R 2 = H (myristicin, 3) methoxybenzene, 5)

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A series of 4-azapodophyllotoxin derivatives with modified rings B and E have been synthesized using allylpolyalkoxybenzenes from parsley seed oil. The targeted molecules were evaluated in vivo in a phenotypic sea urchin embryo assay for antimitotic and tubulin destabilizing activity. The most active compounds identified by the in vivo sea urchin embryo assay featured myristicin-derived ring E. These molecules were determined to be more potent than podophyllotoxin. Cytotoxic effects of selected molecules were further confirmed and evaluated by conventional assays with A549 and Jurkat human leukemic T-cell lines including cell growth inhibition, cell cycle arrest, cellular microtubule disruption, and induction of apoptosis. The ring B modification yielded 6-OMe substituted molecule as the most active compound. Finally, in Jurkat cells, compound induced caspase-dependent apoptosis mediated by the apical caspases-2 and -9 and not caspase-8, implying the involvement of the intrinsic caspase-9-dependent apoptotic pathway.

A number of 5 (1,2,5 oxadiazol 3 yl) 1H tetrazoles were obtained in high yields by reac tions of 3 cyano 1,2,5 oxadiazoles with sodium azide or by nitrosation of furazan based amidrazones, which are easily prepared from the same starting reagents.