David Hands

Unsaturated steroids. Part 6. A route to cholesta-5,7-diene-1α,3β-diol; preparation of steroidal 4,6,8(14)-trienes

Bromination of 5α-cholest-7-en-3-one to give the corresponding 2ζ,4ζ-dibromo-derivative followed by dehydro-bromination gives cholesta-1,4,7-trien-3-one (3). The corresponding cholesta-1,3,5,7-tetraen-3-yl acetate (4) was converted by the method of Kaneko et al. into the adduct of cholesta-1,5,7-trien-3β-ol with 4-phenyl-1,2,4-triazoline-3,5-dione. The corresponding dimethyl-t-butylsilyl ether was transformed into the 1α,2α-epoxide, which was readily converted into cholesta-5,7-diene-1α,3β-diol (8). Treatment of the adduct from a steroidal 5,7-dien-3-one and 4-phenyl-1,2,4-triazoline-3,5-dione with boron trifluoride–ether yields the corresponding 4,6,8(14)-trien-3-one (10).

A synthesis of 1-azabicyclo[2.2.1]heptane-3-carboxylic acid esters in enantiomerically pure form

A novel synthesis of ethyl 1-azabicyclo[2.2.1]heptane-3-carboxylate via 1-benzylperhydropyrano[3,4-c]pyrrol-4-one and 1-benzyl-3-(2-bromoethyl)-4-ethoxycarbonylpyrrolidinium bromide is described. Modification of the method, by incorporation of a chiral substituted benzyl group on the nitrogen atom, has led to the first reported process for the preparation of these esters in enantiomerically pure form. The absolute configuration of the bicyclic esters was deduced by X-ray crystallography of an intermediate, 2-[(S)-1-phenylethyl]perhydropyrano[3,4-c]pyrrole-4-one.

Unsaturated steroids. Part 8. Synthesis of ergosta-5,7-diene-1α,3β-diol, the 4,4-dimethyl analogue, and 4,4-dimethylergosta-5,7-dien-3β-ol

From 5α-ergost-7-en-3-one, by employing the method used2 for the preparation of the cholestane analogue, ergosta-5,7-diene-1α,3β-diol (1; R = Me) has been synthesised. Methylation of ergosta-1,4,7-trien-3-one (2) gave 4,4-dimethylergosta-1,5,7-trien-3-one. The corresponding 1α,2α-epoxide (3), furnished 4,4-dimethylergosta-5,7-diene-1α,3α-diol (4; R =α-OH) and the corresponding 1α,3β-diol (4; R =β-OH). 4,4-Dimethylergosta-5,7-dien-3β-ol has been obtained from 22,23-dihydroergosterol by standard methods.

Unsaturated steroids. Part I. Synthesis of 22,23-dihydroergosterol

Bromination of 5α-ergost-7-en-3-one furnishes a mixture of the 2- and 4-bromo-derivatives which is readily dehydrobrominated to yield the isomeric 5α-ergosta-1,7- and ergosta-4,7-dien-3-ones. Reduction of the enol acetate of ergosta-4,7-dien-3-one yields 22,23-dihydroergosterol. Some reactions of the 22,23-epoxide of ergosterol are reported; the configurational assignment of the 22-hydroxy-group in 3,22-dihydroxyergosterols has been clarified.

UNSATURATED STEROIDS. PART I. SYNTHESIS OF 22,23-DIHYDROERGOSTEROL

Bromierung des Ergostenons (I) mit dem Reagenz (II) liefert ein Gemisch der isomeren Bromide (IIIa) und (IIIb), das bei der Dehydrobromierung ein chromatographisch trennbares Gemisch des Dienone (IV) und (V) gibt.