Lead tetraacetate–iodine oxidation of 23-spirostanols Izabella Jastrze z bska, Jacek W. Morzycki * and Urszula Trochimowicz Institute of Chemistry, University of Bialystok, al. Pilsudskiego 11/4, 15-443 Bialystok, Poland Received 24 October 2003; revised 16 December 2003; accepted 23 December 2003 Abstract—Reactions of 23R- and 23S-23-spirostanols in the 25R and 25S series with lead tetraacetate–iodine were studied. The reactions carried out at low temperature afforded D-seco-iododialdehydes and C 22 lactones, while similar reactions performed in refluxing tetrachloromethane yielded 20-chlorolactones and their 21-acetoxy derivatives irrespective of the hydroxyl group con- figuration at C-23. The reaction mechanisms are discussed. Ó 2004 Elsevier Ltd. All rights reserved. The chemistry of spirostanes was intensively studied during the last century. 1 The reason for this study was the search for an efficient route to medicinally important steroids by degradation of plant sapogenins. 2 The recent revival of interest in the chemistry of spirostanes stems from studies on cephalostatins 3 and the natural products isolated from plants used in traditional medicine. 4 Although many spirostane based natural products have been known for several decades, methods for their synthesis are rather limited. We have recently described the solvolytic reactions of 23-bromospirostanes and 23-spirostanol tosylates. 5 Now, the results of our studies on lead tetraacetate and iodine promoted hypoiodite reactions of 23-spirostanols are reported. The hypoiodite reactions have not been studied yet in the chemistry of spirostanes, except for the Suarez’s iodine[III] oxidative spirocyclization. 6 How- ever, the Hofmann–L€ offler–Freytag reaction of the 23R- 23-nitroamine derived from sarsasapogenin led to functionalization of the 27-methyl group. 7 The starting 23-spirostanols were prepared from the naturally occurring sapogenins: diosgenin and sarsa- sapogenin. Both compounds have an a-oriented 21- methyl group (20S ) and an R configuration at the spi- rocarbon atom; they differ in configuration at C-25 (R for diosgenin and S for sarsasapogenin). The sapo- genins were oxidized to the corresponding 23-oxo derivatives by a known method. 8 Lithium aluminum hydride reduction of the 23-ketones afforded the epi- meric mixtures of 23-alcohols. Each of the 23-alcohols 1–4 (Fig. 1) was separately treated with the oxidizing agent. The transformations of the 23-oxygen radicals were studied in the hope of achieving an efficient remote intramolecular functionalization of the neighboring methyl groups. 9 The inspection of the Dreiding models and the computer assisted molecular modeling (MM þ ) 10 indicated that the oxygen radical generated from the axial 23-hydroxy group (23R) may attack the 21-methyl group and, in the case of the sarsasapogenin derivative, also the 27-methyl group. In contrast, the 21- and 27- methyl groups are too far away from the alkoxy radical derived from the equatorial 23S -23-spirostanols. In this case, the closest methyl group is 18-CH 3 (Table 1). However, the intramolecular functionalization is also possible at C-20. Abstraction of the 20-methine hydro- gen gives the stabilized carbon radical. It must be stressed that the C-20 radical may be formed upon O O O AcO H 1 3 2 4 O O O O AcO OH H O O AcO H 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 R S R R 1 2 3 4 O AcO H OH S S S R Figure 1. The structures of starting 23-spirostanols. Keywords: Lead tetraacetate; Oxidation; Spirostanes; Steroids. * Corresponding author. Tel.: +48-85-7457604; fax: +48-85-7457581; e-mail: morzycki@uwb.edu.pl 0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2003.12.146 Tetrahedron Letters 45 (2004) 1929–1932 Tetrahedron Letters