Oxidation and solvolysis of lumi- and photohecogenin and their derivatives

A Novel Oxidative Cleavage of the Steroidal Skeleton

“…We have shown that syn-dihydroxylation of the sterically hindered D 14,15 -double bond in steroids 3 and 19 is possible under forcing conditions. The observed b-diastereoselectivity is in line with known epoxidation results.…”

“…[14] Therefore, during evaluation of substructures, we targeted a cis-dihydroxylation of the D 14,15 -double bond, because the resulting increase in polarity should strongly influence the solubility. ªSacrificingº the D 14, 15 -double bond in this transformation promised new results concerning the relationship of structure and biological activity of our cephalostatin analogues.…”

“…Although various synthetic studies on the D 14,15 -double bond of homoallylic alcohol 3 and its derivatives have been described, [9,15,16] it is interesting that there are no reports on a syn-dihydroxylation. Therefore, we were not surprised when no reaction occurred on treatment of homoallylic alcohol 3 under the standard osmium tetroxide ± dihydroxylation conditions.…”

“…X-Ray analysis ( Figure 2) finally confirmed the structure of this compound to be the unusual bisketal 12. The formation of this cyclic ketal can be explained as follows: ruthenium tetroxide induces an oxidative cleavage of the D 14,15 -olefin [19] furnishing 14-keto-15-aldehyde 11, which is subsequently masked by an intramolecular ketalisation reaction with the 12a-hydroxy group to afford the observed bisketal 12 (Scheme 2).…”

“…[11] Further transformations gave rise to the diketone 5, which then yielded cytostatically active cephalostatin analogues 6 ± 9 using selective reduction procedures (Scheme 1). [8,12,13] The biological activity of these cephalostatin analogues strengthened our assumptions that the unusual D 14,15 -double bond and the polar spiro ketal region may be of substantial importance for cytostatic activity.…”