Steroids 75 (2010) 1127–1136 Contents lists available at ScienceDirect Steroids journal homepage: www.elsevier.com/locate/steroids Novel steroidal penta- and hexacyclic compounds derived from 12-oxospirostan sapogenins José Oscar H. Pérez-Díaz a , José Luis Vega-Baez b , Jesús Sandoval-Ramírez b , Socorro Meza-Reyes b,∗ , Sara Montiel-Smith b , Norberto Farfán c , Rosa Santillan a,∗∗ a Departamento de Química, Centro de Investigación y de Estudios Avanzados del IPN, Apdo. Postal 14-740, 07000 México D.F., Mexico b Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Ciudad Universitaria, Col. San Manuel, C.P. 72570, Puebla, Pue., Mexico c Facultad de Química, Departamento de Química Orgánica, Universidad Nacional Autónoma de México, Ciudad Universitaria 04510, Mexico D.F., Mexico article info Article history: Received 12 May 2010 Received in revised form 12 July 2010 Accepted 14 July 2010 Available online 22 July 2010 Keywords: 12-Oxosapogenins Polycyclic steroids Intramolecular cyclocondensation abstract The E ring regioselective acid-catalyzed opening of spirostanic sapogenins possessing a carbonyl group at C-12, such as botogenin and hecogenin, provided the new 12,23-cyclo-22,26-epoxycholesta-11,22-diene skeleton, in addition to new compounds of the already known 12,23-cyclocholest-12(23)-en-22-one frameworks. This transformation proceeds in a single step, under slightly acidic conditions. Both, penta- and hexacyclic steroids were obtained with retention of configuration of all asymmetric centers. © 2010 Elsevier Inc. All rights reserved. 1. Introduction Steroidal derivatives have been a rich source of agents with potential pharmaceutical applications that have inspired the syn- thesis of new analogs with increased pharmacological activity. By 1990 about 80% of the drugs used were either natural products or synthetic analogs; nowadays almost 50% of the approved drugs are still based on natural products [1]. The spirostan sapogenins are a particular type of steroidal derivatives, widely spread in plants and some marine organisms, which exhibit a broad range of biological activities [2–5]. These natural products are found as steroidal glycosides (saponins). The sugar moiety is greatly diversified and the carbohydrate units can be obtained through acidic or enzymatic hydrolysis. The steroidal sapogenins have served for many years as cheap raw mate- rial for the pharmaceutical industry in the synthesis of sex and adrenocortical hormones, analogs of vitamin D, anabolics and anti- inflammatory drugs [6–8]. Steroidal sapogenins can be divided into cholestanic, furostanic and spirostanic derivatives; the latter ones contain a particular spiroketal system (E/F rings) at the side chain, which is stabilized by anomeric effects [9]. ∗ Corresponding author. Tel.: +52 22 2229 5500x7382; fax: +52 22 2229 5584. ∗∗ Corresponding author. Tel.: +52 55 5747 3725; fax: +52 55 5747 3389. E-mail addresses: msmeza@siu.buap.mx (S. Meza-Reyes), rsantill@cinvestav.mx (R. Santillan). The variants of 12-oxosapogenins, botogenin (1a) and heco- genin (2a)(Fig. 1) are suitable starting materials for the synthesis of 9,11 and 11,12 steroidal epoxides [10], cephalostatines [2,11] and ritterazines [4,12], compounds with potential application for can- cer chemoprevention; also they have been used in the synthesis of drugs such as cortisone, betamethasone [13,14], as well as the preparation of compounds which are potent cholesterol absorption inhibitors [15]. The C-12 ketone group shows remarkable low reactivity mainly attributed to the steric hindrance caused by the angular C-18 and C- 19 methyl groups in the  face. This hypothesis was corroborated by the reduction of the C-12 carbonyl group with NaBH 4 and by hydrogenation [16–18]. The cleavage of the spiroketal ring has been widely investigated under a great variety of reaction conditions providing different kinds of skeletons, sometimes under similar reaction conditions [19–22]. Suárez and coworkers described for the first time the cleavage of the E ring of spirostanic sapogenins catalyzed by BF 3 obtaining the 22,26-epoxy-5-cholest-22-ene 3 with an excellent yield, from a non-functionalized (25R)-spirostan compound [21]. Singh and Dhar however, obtained the 22,26-epoxycholesta-3,5- dien-16-one skeleton 4, treating diosgenin with BF 3 ·OEt 2 at high temperature [23]. Similar results to those of Suárez were obtained by our work group, thus the 22,26-epoxy-5-cholest-22-en-12- one 5 was prepared by regioselective cleavage of the E ring of (25R)-sapogenins such as hecogenin (Fig. 2) [24,25]. Further stud- ies showed that when the same reaction conditions are applied to sarsasapogenin, a (25S)-sapogenin with a pronounced steric 0039-128X/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.steroids.2010.07.008