Antitumor substance isolation

Problem 23.27 Treatment of ethyl acetoacetate with NaOEt (2 equiv) and BrCHgCH2Br forms compound X. This reaction is the first step in the synthesis of illudin-S, an antitumor substance isolated from the jack-o -lantern, a poisonous, saffron-colored mushroom. What is the stmcture of X ... 

There are numerous examples of intramolecular Heck reactions,151 such as in Entries 10 to 14. Entry 11 is part of a synthesis of the antitumor agent camptothecin. The Heck reaction gives an 11 1 endocyclic-exocyclic mixture. Entries 12-14 are also steps in syntheses of biologically active substances. Entry 12 is part of a synthesis of maritidine, an alkaloid with cytotoxic properties the reaction in Entry 13 is on a route to galanthamine, a potential candidate for treatment of Alzheimer s disease and Entry 14 is a key step in the synthesis of a potent antitumor agent isolated from a marine organism. 

Isolation of Antitumor Substance from Basidiomycete Fungus Agaricus blazei and its Mechanism [5]. 

Nakajima H, Sato B, Fujita T, Takase S, Terano H, Okuhara M (1996) New Antitumor Substances, FR901463, FR901464 and FR901465 I. Taxonomy, Fermentation, Isolation, Physico-Chemical Properties and Biological Activities. J Antibiot 49 1196... 

Takahashi, A., Kurosawa, S., Ikeda, D., Okami, Y., and Takeuchi, T., Altemicidin, a new acaricidal an antitumor substance. I. Taxonomy, fermentation, isolation, and physico-chemical and biological properties, J. Antibiot., 42, 1556, 1989. 

Fr. 1 and Fr. 2 prolonged survival time and increased the survival rate compared to untreated tumor-removed mice Fig. (16) . Xanthoangelol and 4-hydroxyderricn were isolated from the Fr. 1 and Fr. 2, respectively, as antitumor substances Fig. (17) . 

Of physiologically active substances isolated from marine sources, the pyrroloimino-quinone alkaloids family exhibits antitumor activities derived from the unique highly-fused structure. The first synthesis of discorhabdin C (127) was performed by means of an electrochemical method as a key step . The key substrate 128, efficiently prepared starting from 4,4-dimethoxy-5-nitrobenzaldehyde, was submitted to constant current electrolysis (3 mA 4-1.2-1.8 V vi. SCE) in anhydrous MeCN to give rise to discorhabdin C in 24% yield, together with a minor compound 129 (6%) (Scheme 24). After a while, discohabdin C was also synthesized by using PhI(OCOCF3)2-promoted oxidation as a key step. ... 

H. Nakajima, B. Sato, T. Fujita, S. Takase, H. Terano, M. Okuhara, New antitumor substances, FR901463, FR901464 and FR901465. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities, /. Antibiot. 49 (1996) 1196. 

Discovery Pladienolides are 12-membered macrohdes isolated as an antitumor substance by cell-based hypoxia-induced gene expression assay from Streptomyces platensis Mer-11107 [1]. The structures of pladienolide B and D were determined as 1 and 2, respectively [2,3]. Total synthesis of pladienolide B [4] and biosynthetic gene cluster [5] is also reported. 

Discovery Spliceostatin A (1) is a methyl ketal derivative of FR901464 (2), which was isolated as an antitumor substance from the culture broth of bacterium Pseudomonas sp. No. 2663 [1,2]. The structure of FR901464 was determined to be compound 2 on the basis of spectroscopic and chemical evidence [3]. Total syntheses of FR901464 were reported 4-6. 

Yamada, K., Ojika, M., Ishigaki, T., Yoshida, Y, Ekimoto, H., and Arakawa, M. (1993). Aplyro-nine A, a potent antitumor substance, and the congeners aplyronines B and C isolated from the sea hare Aplysia kurodai. J. Am. Chem. Soc. 115, 11020-11021. 

A lot of anticancerous agents have been isolated from natural sources especially from microorganisms and plants. However, there is no one special type of compound for cancer therapy various types of substances are effective for various types of cancers and tumors, for instance, alkaloids, lignans, terpenes and steroids [1]. In this report, concentrates on those antitumor compounds isolated from higher plants. 

The interest generated by polyester sesquiterpenes from the Celastraceae has increased in line with the complexity of the substances isolated and the possibility of their being applied to combat insect plagues instead of synthetic insecticides. These compounds have also attracted a great deal of interest on account of their antitumor-promotion activity. 

Kanamaru T, Nozaki Y, Muroi M (1990) Isolation of antitumor substances TAN-1120 from the culture broth of Streptomyces triangulatus angiostaticus. EP Patent 376177 (Chem Abstr 114 41033)... 

The first report on antibacterial activity of Rabdosia constituents appeared in 1954, when it was discovered that a crystalline substance isolated from the ethanolic extract of Rabdosia japonica inhibited the growth of Gram-positive bacteria (i). Later two groups found that an extract of R, trichocarpa also had antibacterial and antitumor activities 131, 132). It was shown (133) that the activity was due to enmein. Dihydroenmein was inactive, while (9,(9-diacetylenmein remained active. Hence it was assumed that the biologically active site of enmein was the a-methylenecyclopentanone moiety (133). 

J. Antibiot. 1993,46,1799-1803. A new antitumor substance, BE-18591, produced by a streptomycete. I. Fermentation, isolation, physico-chemical and biological properties. 

Remember that this species, which can be regarded as fixed, was discovered through the symbiotic relationship that it maintains with ascidians of the family Didemnidae, in particular Diplosoma similis and D. virens, Lissoclinum patella and I. voeltzkowi, Trididemnum cyclops and, more recentiy, the genus Polysyncraton (Duclaux, Lafargue, and Wahl, 1998). These relations have considerable importance insofar as the Didemnidae frequently contain antiviral and antitumor substances whose true origin is probably Prochloron. In our current state of knowledge, it has not yet been possible to cultivate in vitro-isolated... 

Several genera of Scleractinia of the family Dendrophyl-lida Astroides, Dendrophyllia, Leptopsammia, Tubastrea) have yielded indolic derivatives, most of which are bromi-nated and are derived from aplysinopsin, an antitumor alkaloid isolated from the dictyoceratid sponge Aplysinopsis reticulata (see Chapter 19). These substances are frequently encountered in the marine environment but seem characteristic of this family of hard corals, some examples of which are shown in Figure 20.73. 

The dicytodendrins A-E (Fig. 9) are one of the most recent 3,4-diarylpyrrole natural products to be reported [64], Their isolation by Fusetani and coworkers from a Japanese marine sponge was reported in 2003. These substances (144-148) have been shown to inhibit telomerase at a concentration of 50 pg/mL thereby making such compounds potentially useful as antitumor agents given that telomerase activity is found in 90% of cancer cells but... 

The substance with the antitumor activity in the n-hexane-insoluble fraction was isolated through silica gel column chromtography, eluted with an acetonitrile/methanol (3 2) mixture and identified as ergosterol Fig. 

The investigation of microorganisms has also resulted in the isolation of numerous indole derivatives with antibiotic and antitumor activity as well as substances primarily noteworthy for toxicity. One example is the mitomycin family, which has antitumor activity. Mitomycin... 

Manzamines comprise a new group of /3-carboline alkaloids having polycyclic ring systems, the provenance of which is problematical as there appears to be no obvious biogenetic path. Manzamine A (180) was isolated from an Okinawan sponge (Haliclona sp.) and shown to exhibit antitumor activity. Its structure and absolute configuration were determined by X-ray analysis (150). From an Okinawan sponge (Pellina sp.) keramamines A (180) and B (181) were isolated as antimicrobial substances (151), and keramamine A was found to be identical with manzamine A. 

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