Controlled Red-Ox Reactions of Certain Cephalostatin analogs with anti-Cancer Activity Mansour Nawasreh  Applied Sciences Dept., Faculty of Engineering Technology, Al-Balqa Applied University, P. B. 15008, Amman 11134 Jordan. Abstract. We broadened the transformation varieties of some bis-steroidal pyrazines as analogs to cephalostatine 1, which is a remarkable antineoplastic natural product isolated from the marine algae Cephalodiscus gilchristi. It is a small molecule with a unique cytotoxicity profile in the in vitro screen system of the National Cancer Institute, suggesting that it may affect novel molecular target(s). In this part of the work, the regioselectivity of F-ring reductive-opening was discovered for an analog and improved for another analog by using some borane-complexes. Looking for enhancement of biological activity, an α,β- unsaturated carbonyl was generated by oxidation of allylic position of a methylene group at C-12 to be as Michael receptor. Keywords: cephalostatin1, F-ring reductive-opening process, regioselectivity, α, β-unsaturated carbonyl, Michael receptor. 1. Introduction Cephalostatin 1 1, is a potent tumor inhibitory marine natural product isolated by Pettit’s group at Arizona State University from Cephalodiscus gilchristi in addition to other 18 compounds belonging to the same family [1]-[4]. This group of compounds sharing the same backbone which consists of two steroids coupled to each other through pyrazine ring. Cephalostatin 1 is a small molecule suggested to affect novel molecular target(s) and with a unique cytotoxicity profile in the in vitro screen system of the National Cancer Institute. Aiming at the synthesis of cephalostatin analogues with high biological activity, we reported here a new methods either to improve the regioselectivity of F-ring opening process, which was previously investigated [5], [6] or to generate α, β-unsaturated system on Ring-C as Michael receptor. This work is a part of a strategy aimed at understanding the chemistry of such bis-steroidal system, which we hope to enable us to achieve a total synthesis of one or more of the cephalostatin natural products. The first total synthesis of Cephalostatin 1 was reported by Fuchs and his coworkers in 1998 [7]. Moreover, through this work we were able to gather more information about structure-activity relationship, since most of the synthesized compounds were tested against three representative cancer cell lines (HM 02, HEP G2, MCF 7). In Jurkat leukemia T cells, cephalostatin 1 was found to induces a novel pathway of receptor-independent apoptosis that selectively uses Smac/ DIABLO as a mitochondrial signaling molecule. [8] 2. Results and Discussion As a completion of our previous work, new routes were examined looking for selective reactions to desymmetrize the symmetrical diketone 2, which can be prepared in gram scale using a well established method [9 and references therein]. The researcher is aiming at the synthesis of high biological active analogues to the cephalostatin 1 1.  Corresponding author. Tel.: +962 6 4790333 ext. 274; fax: +962 6 4790350 E-mail address: mansreh@yahoo.com 2014 3rd International Conference on Environment Energy and Biotechnology IPCBEE vol.70 (2014) © (2014) IACSIT Press, Singapore DOI: 10.7763/IPCBEE. 2014. V70. 8 43