Natural products antitumour activity

The synthesis of the naphthalene rings found in the gilvocarcin group and in the rubromycin class of natural products via benzannulation was also reported. Both classes show promising antitumour activity [67,68]. 

Peroxy derivatives of steroids have been isolated from both marine and terrestrial sources. They are most commonly 5a, 8a-endoperoxides with variations in the side-chains. The ergosterol peroxide 102 is the most ubiquitous endoperoxide-containing natural product and is isolated from a large number of sources. Ergosterol peroxide 102 was found to have antitumour activity against breast cancer and carcinosarcoma cell lines. A number of other steroidal endoperoxides have been reported which differ in the nature of the side-chain. Compound 103 was found to be an inhibitor of tumour promotion in mouse studies . 

It is a diterpenoid compound and is a natural product with antitumour activity. 

Other marine natural products with potent antitumour and antiviral activities, the eudistomins, continue to attract attention. As part of a new synthetic approach to the eudistomins, the stereoselective formation of the P-lactam fused oxathiazepine 110 has been reported <03SL738> C-N bond formation from 106 (via 105) was used to complete the seven-membered ring, and then this product 107 was converted into 110 via 108 and 109. Unfortunately, after ring opening the P-lactam in 110 and setting up the substituents for indole ring formation, this crucial indolisation was not successful. Other pathways are being explored but the P-lactam precursor concept is a clever one. 

This observation was vital in developing a synthesis of varrucarin A, a natural product with antitumour activity (B. M. Trost and P. G. McDougal, J. Org. Chem., 1984, 49, 458). 

Some natural products contain an aziridine ring, e.g. mitomycins (3 mitomycin C). This is responsible for the cytostatic and antitumour activity of these antibiotics. Many synthetic aziridines have been screened for their antitumour activity. Some have reached the clinic, especially as antileukaemic agents, e.g. 4 and 5. 

Spirocyclic C-aryl glycosides and styryllactones are carbohydrate-based lactones. Spirocyclic C-aryl glycosides are isolated from a strain of Papularia sphaerosperna and constitute a family of novel antifungal antibiotics. They serve as an excellent antifungal agent against Candida tropicalis, Candida albicans and Pneumocystis carinii. Styryllactones are enantiomers of ([))-altholactone, a natural product which possesses antitumour and cytotoxic activities. 

The antitumour activity of tetrahydrofuran (THF) containing acetogenins has led to development of new functional THFs and non-adjacently linked bis-TFIF derivative synthesis. BuUatanocin 84 is one of the latter and was recently prepared by CM [64] (Scheme 32). Treatment of 80 and 81 in tiie presence of Grubbs catalyst 3 led to the bridged derivative 82. Subsequent hydrogenation (Pd/C) and Wittig reaction with 83 led to the natural product bullatanocin 84. 

The platinum—pyrimidine blues, derived from cisplatin, are an interesting class of complexes with antitumour activity. They were first discovered as a result of studies on the interaction of c/ [PtCl2(NH3)2] and its aquated products with pyrimidines. The identification of DNA as the target for platinum attack naturally led to a systematic study of the reactions of the complex with nucleic acid constituents. The observation that with polyuridine no immediate reaction took place but that a blue color slowly developed in solution, from which a blue solid could be isolated, led to the preparation of a series of complexes containing substituted uracils and thymines. 

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