Synthesis of 23-Oxa-22-deoxo Analogues of OSW-1 Aglycone * by Anna Kruszewska, Agnieszka Z. Wilczewska, Agnieszka Wojtkielewicz and Jacek W. Morzycki ** Institute of Chemistry, University of Bia³ystok, al. Pi³sudskiego 11/4, 15-443 Bia³ystok, Poland (Received October 24th, 2005; accepted December 12th, 2005) Four ether analogues of OSW-1 aglycone were obtained by alkylation of a steroid alcohol with alkyl bromide. During the Williamson reaction promoted by sodium hydride in addi- tion to alkylation, an unusual dehydrogenation of secondary alcohol was observed. Key words: OSW-1, Williamson reaction, dehydrogenation, antitumor agent Among the natural products with antitumor activity discovered during last thirty years, saponin OSW-1, with IC 50 values between 0.1–0.3 nM and GI 50 = 0.78 nM, belongs to the most active ones [1]. It was isolated, as main component, from bulbs of Ornithogalum saundersiae by Sashida nad coworkers in 1992 [2]. Its extraordinary cytostatic activity in connexion with its low toxicity to normal cells (for human pul- monary cell: IC 50 = 1500 nM) stimulated research groups from different countries to elaborate methods of synthesis of this natural product and its analogues for biological studies. So far, four procedures of OSW-1 synthesis have been described [3] and vari- ous analogues have been obtained [4]. The initial structure-activity relationship stud- ies (SAR) demonstrated [4] that both aglycone and sugar structures are important for cytotoxic activity. In sugar part, the presence of acyl groups was necessary for strong activity. In aglycone, the inversion of 16b-OH configuration resulted in significantly reduced potency. Similar lost of activity was observed when the 3-hydroxyl group was acylated. The changes in the side chain are widely tolerated. In the case of some tumor lines even analogues without carbonyl group at C-22 showed comparable ac- tivity to OSW-1. Last report revealed that compounds containing oxygen atom in- stead of carbon atom in position 23 were equally or even more potent than the parent saponin. Polish J. Chem., 80 , 611–615 (2006) * Presented at 21st Conference on Isoprenoids, September 23–29, 2005, Bia³owie¿a, Poland. ** Author for correspondence. E-mail: morzycki@uwb.edu.pl