Current Organic Chemistry, 2006, 10, 2227-2257 2227 1385-2728/06 $50.00+.00 © 2006 Bentham Science Publishers Ltd. Catalytic Oxidative Processes in Steroid Chemistry: Allylic Oxidation,  - Selective Epoxidation, Alcohol Oxidation and Remote Functionalization Reactions Jorge A.R. Salvador*, Samuel M. Silvestre and Vânia M. Moreira Laboratório de Química Farmacêutica, Faculdade de Farmácia, Universidade de Coimbra, Rua do Norte, 3000-295 Coimbra, Portugal Abstract: The preparation of steroids containing oxygenated functions in suitable positions of the steroid nucleus is of great importance and can be achieved by means of several oxidative processes. In this paper allylic oxidation, -selective epoxidation, alcohol oxidation and remote functionalization reactions in steroid substrates are reviewed. Focus has been given to catalytic processes because of their major importance from the viewpoint of synthetic organic chemistry. 1. INTRODUCTION Steroid compounds are widely distributed in nature. The living organism, both animal and vegetable, contains steroids which play an important role in its vital activity. Over the last decades, hundreds of steroid compounds have been isolated from natural sources and many thousands of them have been obtained synthetically. Moreover, steroids are challenging substrates for the synthesis of a wide variety of important biologically active molecules. The preparation of steroids containing oxygenated functions in the steroid nucleus is of major importance and can be performed by means of several oxidative processes. Among the available methods, allylic oxidation, -selective epoxidation, alcohol oxidation and remote functionalization reactions were chosen to discuss in this review. Special emphasis has been given to the allylic oxidation of steroidal alkenes to the corresponding enones. The  5 -7-keto deri- vatives are of great importance due to their relevant bio- logical properties. -Selective epoxidation has been consi- dered because the -epoxides are normally difficult to obtain in organic synthesis. Moreover, this functionality has been found in a number of biologically active steroids, parti- cularly the 5,6-epoxides. The oxidation of steroidal satu- rated, allylic and homoallylic alcohols is also reviewed. Of particular relevance is the synthesis of  4 -3-ketones, a typical functionality of the major class of steroidal hor- mones. Finally, remote functionalization in steroid substrates has been considered. Its practical goal lies in the possibility of obtaining bioactive compounds from readily available sterols or bile acid sources, through regio- and stereo- selective remote oxyfunctionalization of unactivated carbons, avoiding multistep syntheses. Environmentally benign and sustainable transformations are now considered to be basic goals and requirements in the development of modern organic synthesis. There has been a growing effort in the replacement of stoichiometric pro- cedures, using classical toxic waste-producing oxidants, with *Address correspondence to this author at the Laboratório de Química Farmacêutica, Faculdade de Farmácia, Universidade de Coimbra, Rua do Norte, 3000-295 Coimbra, Portugal; Tel: +351 239859950; Fax: +351 239827126. E-mail: salvador@ci.uc.pt catalytic procedures using environmentally friendly oxidants. These include molecular oxygen, hydrogen peroxide, alkyl hydroperoxides, nitrous oxide and several other systems where there is either no by-product, the by-product is environmentally benign or it can easily be recovered and recycled. For synthetic utility, where high conversion and selectivity are desirable, these oxidants require activation by appropriate, usually metal-based catalysts. Furthermore, it is preferable to carry out these reactions in aqueous media or organic solvents with low environmental load. The recycling of both catalysts and solvents is also highly desirable [1]. For these reasons, in this review focus has been given to catalytic oxidative processes. Each section contains brief mention of the biological relevance of some of the compounds that can be prepared using the reactions chosen and a basic description of the stoichiometric processes involved. The biocatalytic oxidative processes available to perform these reactions have not been included in this review. 2. ALLYLIC OXIDATION Allylic oxidation is a particularly important subject and has attracted interest over many years. This consists of the production of allylic alcohols, esters, ethers and ,- unsaturated carbonyl compounds [2]. In this review, focus has been exclusively given to the allylic oxidation of steroidal alkenes to the corresponding enones, mainly because this functionality is present in a large number of biologically active steroids. An example of the former is the oxidation of  5 -steroids to their corresponding  5 -7-ketones (scheme 1) [3]. These compounds can be found in animal tissues, food products [4] and certain folk medicines [5], and some are known inhibitors of sterol biosynthesis [3a; 4b; 6]. Their greater toxicity towards cancerous than non-cancerous cells [5b] as well as their ability to inhibit cell replication [7] are probably the dominant reasons they are considered potent agents for cancer treatment. 7-Keto-dehydroepiandrosterone (7-keto-DHEA) 8 and some of its derivatives are effective in inducing thermogenic enzymes [8]. Enhancement of memory in old mice by 7- keto-DHEA acetate 6 has been reported [9]. This compound is currently available as a nutraceutical [10] and is suggested to be useful in the prevention of primary Raynaud's attacks