Further study on oxidation of pseudosapogenins

6 β -Methoxy-3 α ,5-cyclo-5 α -furost-20(22)-ene ( 4 ) and its 26-tosyloxy derivative ( 3 ) were oxidized with m -chloroperoxybenzoic acid, dimethyldioxirane and osmium tetroxide. The reaction of 4 with MCPBA yielded the allylic alcohol 6 , the α , β -unsaturated ketone 7 and the α -hydroxy-lactone 8 . Similar reaction of 3 carried out in a buffered medium led to the products 9 and 10 with the C20-C22 bond cleaved. The reaction of the same compound with dimethyldioxirane afforded the allylic alcohol 5 . The oxidation of pseudosapogenins with OsO 4 gave dihydroxylation products 11 and 12 .


Introduction
2][3] The immense commercial significance of spirostanol saponins as raw materials for steroid production stems from the discovery by Marker that their aglycones can be easily converted into pregnane derivatives.An excellent historical perspective on the chemistry of Russell Marker was recently described. 4The Marker degradation includes acetolysis of the spiroketal moiety followed by an oxidative cleavage of the double bond in the resulting furost-20-enes (pseudosapogenins).The most important sapogenin from an economic standpoint is diosgenin that is extracted from Dioscorea species.Oxidation of the corresponding pseudosapogenin with various reagents, such as CrO 3 /AcOH, KMnO 4 /NaIO 4 or H 2 O 2 /AcOH has been intensively studied. 5,6These reactions lead to 16-dehydro-pregnane derivatives by cleavage of the E ring.They are key intermediates in the synthesis of steroid hormones, particularly corticosteroids and sex hormones.Some polyhydroxy cholestane derivatives have been recently reported to show interesting biological properties (e.g.8][9] The aim of this study was to explore the possibility of application of spirostanols as starting materials for the synthesis of polyhydroxy cholestane derivatives with the hydroxy groups in the positions 16, 20, 22 and 26.

Results and Discussion
A conversion of the starting diosgenin 1 into furost-20(22)-enes 3 and 4 was performed as shown in Scheme 1 and was described in our previous paper. 10

Scheme 1
Compound 4 was treated with MCPBA (Scheme 2).The initial reaction product was presumably the corresponding epoxide, but this proved insufficiently stable under the reaction conditions to be isolated from the reaction mixture.Instead the epoxide readily opened up to yield the allylic alcohol 6 (Z-configuration at the C22-C23 double bond was established by the NOE enhancement of the 21-methyl protons signal on irradiation of 23-H).Further oxidation of 6 with MCPBA gave the α,β-unsaturated ketone 7. On prolonging the reaction time, the slow disappearance of both products 6 and 7 was observed in favour of the α-hydroxy-lactone 8.All attempts to isolate the intermediate epoxide under the milder reaction conditions failed.Even MCPBA oxidation performed in a buffered medium (NaHCO 3 ) 11 yielded products derived from opening of the intermediate epoxide.For example, the reaction of compound 3 afforded esters 9 and 10, as well as the α-hydroxy-lactone 8.The latter product was identical to the compound obtained from the reaction of 4 with MCPBA.The key step of the reaction carried out in the buffered medium, similarly as in the previous case, was the cleavage of the 20,22-epoxide to the allylic alcohol 5.However, further oxidation of 5 with excess MCPBA proceeded in a different way in the presence of NaHCO 3 .The reaction resulted in the cleavage of the C20-C22 bond via a mechanism shown in Scheme 3. In a separate experiment it was found that the hydroxy-tosylate 10 does not cyclize to 9 under the reaction conditions, rather the furan ring closure took place at an earlier stage, presumably by rearrangement of an epoxy-tosylate.
Scheme 3 Scheme 4 Therein we present the oxidation of compounds 3 and 4 with different reagents (m-chloroperoxybenzoic acid, dimethyldioxirane, and OsO 4 ).
~0.35 mmol) in dichloromethane (2 mL) were added.The reaction mixture was stirred for 3 days at room temperature, quenched by addition of aqueous solution of sodium sulfide, and extracted with chloroform.The extract was dried over anhydrous magnesium sulfate and the solvent was evaporated in vacuo.The products were separated by silica gel column chromatography.
mmol) and three drops of 10% solution of OsO 4 in benzene were added.The reaction mixture was stirred at room temperature for 3 days, then an aqueous solution of sodium hydrogen sulfite (2 mL, 40%) was added.The reaction mixture was stirred at room temperature overnight, poured into water and extracted with ether.The extract was dried over anhydrous magnesium sulfate and the solvent was evaporated in vacuo.The residue was purified by silica gel chromatography.