THE ISOMERIZATION OF Δ^{7, 22}-ERGOSTADIENOL WITH COPPER CHROMIUM OXIDE

Abstract

Nearly twenty-five years ago Reindel and Walter (1) discovered that 6 -7• 22ergostatrienyl acetate (lb, ergosteryl acetate) absorbed two moles of hydrogen when reduced in ethereal solution, with platinum black as catalyst, to give A8(lt)-ergostenyl acetate (Vb, -ergostenyl acetate). Simultaneously with the saturation of the 5,6 and 22,23 double bonds a shift of the double bond from 7,8 to 8,14 took place. The isomerization has also been effected (2) starting with A7-ergostenol (Via, -ergostenol). Despite the more recent and rather extensive investigations of this subject, notably by Wieland and Benend (3) and by Barton and co-workers (4, 5, 6), the rearrangement of the nuclear double bond has not been accomplished without hydrogenation of the side chain double bond. Indeed, the expected product, namely 8(14) • 22-ergostadienol (Ilia, ß-dihydroergosterol), has not been obtained in a pure state by any isomerization procedure. Heilbron and co-workers ( 7) and Dithmar and Achtermann (8) reported its preparation by isomerization with dry hydrogen chloride, but Barton and co-workers (6) have shown that under these conditions the product obtained is an inseparable equimolecular mixture containing the further isomerized compound, 14• 22ergostadienol.We have been able to obtain 8(14) • 22-ergostadienol (Ilia) in a 54% yield by direct isomerization of 7• 22-ergostadienoll (Ila, -dihydroergosterol) using a copper chromiun oxide catalyst (10) in the presence of hydrogen. The compound was accompanied by a crystalline by-product which probably has a 3-a-hydroxyl group. The complete structure of this latter material is under investigation. The structure of Ilia was indicated by its hydrogenation to A8(14)-ergostenol (Va) under conditions which do not normally lead to isomerization, and by the agreement of its molecular rotation with the calculated value.2 While this work was in progress, Laubach and Brunings (9c) reported the preparation of 8(14) 22-ergostadienyl acetate (Illb) by 1,2 addition of hydrogen to 6•8(14) • 22-281 spectra which have been used in this work. We also thank Mr. Robert Kostic for technical assistance. SUMMARY 1. 7-22-Ergostadienol ( -dihydroergosterol) has been isomerized in the presence of copper chromium oxide and hydrogen to 8(14) 22-ergostadienoI.2. Hydrogenation with copper chromium oxide or Raney nickel reduced the A9(11)-bond of the 7•9(u)-diene system in ergosterol-D. Bethbsda 14, Maryland