V. L. Novikov

Synthesis of some hydroxynaphthazarins and their cardioprotective effects under ischemia-reperfusion in vivo

A series of hydroxynaphthazarins has been synthesized. Some of them were found in in vivo experiments to be protectors of myocardium under ischemia-reperfusion and to reduce the infarction zone by 50% without any adverse effect. All compounds exhibit a moderate or small toxicity and are active in low doses.

A simple and practical approach to the synthesis of the marine sponge pigment fascaplysin and related compounds

Fascaplysin 1, an antimicrobial and cytotoxic red pigment of the marine sponge Fascaplys-inopsis sp., has been synthesized in five steps from tryptamine 2 in 44% overall yield. The key steps in the synthesis are: (a) dehydrogenation of the dihydro-β-carboline intermediate 4 simultaneously with its benzylic oxidation on treatment with MnO2 and (b) the thermal cyclization of the resulting β-carboline 7 into a quaternary salt 8. Similarly, indoloisoquinolines 15 and 16, the tetracyclic analogues of 1, were prepared in six steps from α-amino ketone 9 in 59 and 55% overall yields, respectively.

Fluoride salts-alcohols-alumina as reagents for nucleophilic substitution of chlorine atoms for alkoxy groups in 2,3-dichlorosubstituted juglones, naphthazarines, and quinizarines

Abstract Direct displacement of chlorine atoms by alkoxy groups in 2,3-dichlorosubstituted juglones (5-hydroxy-1,4-naphthoquinones), naphthazarines (5,8-dihydroxy-1,4-naphthoquinones), and quinizarines (1,4-dihydroxy-9,10-anthraquinones) is generally ineffective, however high yields are obtained when methanol or cellosolves activated by fluoride anion are used as nucleophiles and the reaction goes in the presence of alumina.

Synthesis of polycarpine, a cytotoxic sulfur-containing alkaloid from the ascidian Polycarpa aurata, and related compounds

Polycarpine 1, a highly cytotoxic marine natural product, has been synthesized in three steps from p-methoxyphenacyl bromide 4 in 57% overall yield. The key reaction for construction of the symmetrically substituted disulfide linkage of polycarpine is the treatment of 2-amino-4-(4-methoxyphenyl)-1-methylimidazole 17 with S2Cl2 in acetic acid. In a similar way ten related compounds, including three thiazole analogues, have been prepared. Most of them exhibit high cytotoxic activities against an array of human cancer cell lines.

INHIBITION OF MEMBRANE TRANSPORT ATPASES BY HALENAQUINOL, A NATURAL CARDIOACTIVE PENTACYCLIC HYDROQUINONE FROM THE SPONGE PETROSIA SERIATA

Halenaquinol, a natural cardioactive pentacyclic hydroquinone from the sponge Petrosia seriata, was found to be a powerful inhibitor of the rat brainstem and of the rat brain cortex Na+, K(+)-ATPases and the rabbit muscle sarcoplasmic reticulum Ca(2+)-ATPase with I50 values of 7.0 x 10(-7), 1.3 x 10(-6) and 2.5 x 10(-6) M, respectively. Halenaquinol also inhibited K(+)-phosphatase activity of the rat brain cortex Na+, K(+)-ATPase with an I50 value of 3 x 10(-6) M. Ouabain-insensitive Mg(2+)-ATPase activity of the microsomal fraction of the rat brain cortex was weakly inhibited by halenaquinol. Inhibition was irreversible, dose- and time-dependent. Naphthohydroquinone fragment in structures of halenaquinol, related natural and model compounds was very important for an inhibiting effect.

A Convenient Method for the Selective Alkylation ofβ-OH Groups of 2(3)-Hydroxyjuglones and Hydroxynaphthazarines

Abstract Trimethyl-and triethylorthoformates have been used for the selective alkylation of β-OH groups of 2(3)-hydroxy-3(2)-alkyljuglones, 2-hydroxy-3-alkyl-, 2-hydroxy-3-chloro-, and 2,3-dihydroxynaphthazarines (1a-o,3,4). In most cases the corresponding alkoxy compounds (2a-q,5,6) were obtained in good yields. However, when 2-hydroxynaphthazarine (1p) was used, the formation of monomethineoxonol derivative (9) as the principal product took place.

The Reductive Dehalogenation of Halo-Substituted Naphthazarins and Quinizarins as a Simple Route to Parent Compounds

Abstract By the reaction of 2-chloro-3-alkyl-, 2,3-dichloro(dibromo)-, trichloro-(tribromo)-and tetrachloro(tetrabromo)-naphthazarins and 2,3-dichloroquinizarin with Fe/HOAc followed by oxidation with an air in a mild basic conditions the corresponding naphthazarins and quinizarin were obtained in good to excellent yields.

A new triterpene from the leaves ofBetula mandschurica

A new triterpene (I) has been isolated from the unsaponifiable fraction of an ethereal extract of the leaves ofBetula mandschurica to which, on the basis of the results of a physicochemical investigation and a comparison of the13C spectra with the spectra of known triterpenes — ocotillone (II) and 20(S)-hydroxydammar-24-en-3-one (III) — the structure of 20(S),24(S)-dihydroxydammar-25-3n-3-one has been assigned. An approach to the determination of the configuration of the asymmetric center at C24 in 24-hydroxy derivatives of tetracyclic triterpenoids with an open side chain by the use of13C NMR spectroscopy is proposed.

The Cytotoxic and Antitumor Activities of the Imidazole Alkaloid Polycarpin from the Ascidian Polycarpa aurataand Its Synthetic Analogues

Effective cytostatics and selective inhibitors of the key biochemical processes that are isolated from marine invertebrates are more and more widely used in modern cell biology and medicine [1–5]. It is not surprising that, in solving one of the main problems of modern clinical oncology—the problem of multiple resistance of tumors to drugs—the researchers are counting on the natural compounds from marine hydrobionts whose action is directed to new cell targets. A special attention is paid to marine alkaloids. It will suffice to mention two new antitumor preparations from marine invertebrates: ecteinascidin-743, a tetrahydroisoquinoline alkaloid from the ascidian Ecteinascidia turbinata [1, 5]; and ascididemin, a pentacyclic pyridoacridine alkaloid from the ascidian Cystodytes dellechiajei and a number of ascidians of the genus Didemnum [4], which have already passed the main stages of clinical trials in Europe and the United States. The mechanisms of action of these alkaloids on the tumor cells differ from the mechanisms known for antitumor genotoxic preparations. This may account for the high effectiveness of ecteinascidin and ascididemin against tumors with multiple resistance to drugs, which opens up new fields of successful use of other marine natural compounds as chemotherapeutic drugs of a new generation.

Synthesis of shikalkin and certain related compounds

A successful total synthesis of a biologically active pigment from plants of the Boraginaceae family was carried out with naphthazarine as the starting material, and using the 1,4,5,8-tetramethoxynaphthalene, the corresponding 2-vinyl derivative and its epoxide or a cyclopropane adduct with diazoacetic ester at the key stages. In the course of developing the scheme of the synthesis of shikalkin, its three analogs were obtained, differing in the nature of the monoterpenoid side chain.