Dimeric steroids

When intermediate 274 reacted with ketones 133 (from D-glucose) or 270 (from D-fructose), mixed steroid-sugar compounds 278 and 279 were, respectively, obtained in low yields (10-16%). In addition, the use of protected estrone 280 (precursor of the epoxide 272) as electrophile allows the preparation of the dimeric steroid 281 in 26% yield. The low yields obtained for compounds 278, 279 and 281 are due to extensive decomposition during their column chromatographic purification. 

Cephalostains 1-6 (507-512), powerful cell growth inhibitory substances against the PS cell line, were isolated from the marine worm Cephalodiscus gilchristi collected in the Indian Ocean 406-408). The structure of cephalostatin 1 (507) was determined by X-ray analysis. Cephalostatins apparently result from a biosynthetic condensation of 2-amino-3-oxosteroid units to yield dimeric steroidal molecules connected by a pyrazine ring. 

Fukuzawa, S., Matsunaga, S., and Fusetani, N., Ritterazine A, a highly cytotoxic dimeric steroidal alkaloid, from the tunicate Ritterella tokioka, J. Org. Chem., 59, 6164, 1994. 

J.W. Morzycki and co-workers described the synthesis of dimeric steroids to be used as components of artificial lipid bilayer membranes. The key coupling of two steroid derivatives was achieved by the Wurtz reaction. The steroid primary alkyl iodide was dissolved in anhydrous toluene and treated with an excess of sodium metal. After 20h of reflux, the desired homocoupled product was obtained in moderate yield along with a considerable amount (36%) of the reduced compound. 

Morzyeki, J. W., Kalinowski, S., Lotowski, Z., Rabiezko, J. Synthesis of dimeric steroids as components of lipid membranes. Tetrahedron 1997,53, 10579-10590. 

Fuchs et al. have also synthesized the trisdecacyclic pyrazines (52-54) from commercially available 3/3,12/3-diacetoxy-5a-spirostan-ll-one in 13-24% overall yields (38). It is important to remember that all cephalostatins and ritterazines have a trisdecacyclic dimeric steroidal skeleton. The efforts of Fuchs et al. represent the first studies directed at the total synthesis of this bissteroidal skeleton (38). 

When Two Steroids are Better than One The Dimeric Steroid-Pyrazine Marine Alkaloids... 

The family of dimeric steroid-pyrazine alkaloids isolated from Cephalodiscus and Ritteria now stands at thirty members. There are undoubtedly other examples of this group of steroidal alkaloids that have yet to be discovered, and it is probable that members common to both sources will be found. 

The pioneering paper on metabolites from sponges of Theonella genus appeared in literature in 1981 dealing with the isolation of two new and unusual sterols with the unprecedented 4-methylene nucleus, conicasterol (2) and theonellasterol (3) [3]. Subsequently, the 3-keto derivatives, conicasterone (4) and theonellasterone (5), together with a Diels Alder type dimeric steroid, named bistheonellasterone (6), were reported from the Okinawan marine sponge Theonella swinhoei [4], It is noteworthy that... 

The ritterazines are highly ox ygenated dimeric steroidal alkaloids isolated by Fusetani and co-workers from 1994 to 1997 from the colonial tunicate Ritterella tokioka (family Policlinidae) [107, 108],... 

Ganesan, A., 1996. The dimeric steroid-pyrazine marine alkaloids challenges for isolation, synthesis, and biological studies. Angew. Chem. Int. Ed. Engl 35, 611-615. 

The cephalostatins are a group of cytotoxic dimeric steroid derivatives from the marine worm Cephalodiscus gilchristi. Tietze and Krahnert prepared a group of natural product analogs using multiple Heck reactions using derivative 106 obtained from the Hajos-Wiechert reaction their approach is outlined below. ... 

Ganesan, A. (1996) When two steroids are better than one the dimeric steroid-pyrazine marine alkaloids, in Studies in Natural Products Chemistry, vol. 18 (ed. Atta-ur-Rahman), Elsevier Science, Amsterdam, Oxford, New York, pp. 875-906. 

Kobayashi, M., Kawazoe, K., Katori, T, and Kitagawa, I. (1992d) Two new 3-keto-4-methylene steroids, theonellasterone and conicasterone and a Diels-Alder-type dimeric steroid bis-theonellasterone, from TheoneUa swinhoei. Chem. Pharm. Bull., 40, 1773-1778. 

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