steroids 71 ( 2 0 0 6 ) 116–119 available at www.sciencedirect.com journal homepage: www.elsevier.com/locate/steroids Steroidal seven-membered A-ring epoxy lactones by oxidation of the corresponding  4 -3-ketosteroids Maria L. Di Gioia, Antonella Leggio, Adolfo Le Pera, Francesca Perri, Andrea F. Pitrelli, Angelo Liguori * Dipartimento di Scienze Farmaceutiche, Universit` a degli Studi della Calabria, Via Ponte P. Bucci, Cubo 15/C, I-87036 Arcavacata di Rende (CS), Italy article info Article history: Received 13 April 2005 Received in revised form 1 September 2005 Accepted 1 September 2005 Available online 13 October 2005 Keywords:  4 -3-Ketosteroids Seven-membered A-ring epoxy lactone m-Chloroperbenzoic acid Oxidation abstract Treatment of  4 -3-ketosteroids with m-chloroperbenzoic acid at 0 ◦ C produced the corre- sponding steroidal seven-membered A-ring epoxy lactones. The adopted procedure allowed for efficient recovery and separation of the products with definite stereochemistry. © 2005 Elsevier Inc. All rights reserved. 1. Introduction Steroids, possessing a seven-membered A-ring epoxy lactone are important precursors to obtain eight-membered-ring ana- logues, characterized by considerable biological activity that have been usually produced via the Tebbe and Claisen reac- tions [1]. They represent useful intermediates for the synthesis of steroidal molecules with the A-ring replaced by an appro- priately substituted open chain [2]. Various procedures for the oxidation of differently func- tionalized  4 -3-ketosteroids are reported. With all of these methodologies, however, other oxidation products and, in some cases, the epoxy lactones were obtained in complicated mixtures with a large variety of products. Different oxidizing agents were tested on substrates carrying a protecting group on the functionalities of the steroid skeleton. Very low yields ∗ Corresponding author. Tel.: +39 0984 492042; fax: +39 0984 492855. E-mail address: a.liguori@unical.it (A. Liguori). were observed when steroids underwent the oxidation reac- tion without functional group protection. In particular, treat- ment of  4 -3-ketosteroids with hydrogen peroxide in the pres- ence of sodium hydroxide or tert-butyl hydroperoxide in the presence of lithium hydroxide, at room temperature, afforded the corresponding 4,5-epoxides stereospecifically without enlargment of the A-ring [3]. Treatment of  4 -3-ketosteroids with lithium peroxide produced the 4,5-epoxides in low yield together with an A-nor-3,5-secoacid, while treatment with sodium peroxide led to the production of the corresponding  4 -3,6-diones. Under the conditions employed, there was no evidence for the formation of epoxy lactones [3]. The oxidation of 19-substituted  4 -3-ketosteroids with m-chloroperbenzoic acid at room temperature for 11-days led to a lactol compound and to a 3,19-lactone derivative via a non-isolated epoxy lac- tone intermediate [4]. Oxidation of testosterone acetate with 0039-128X/$ – see front matter © 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.steroids.2005.09.003