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The significance of the biosynthetic pathway, cholesterol -> 20a-hydroxy cholesterol -*• pregnenolone -* progesterone -* cardenolides, in plants has been examined by the simultaneous administration of a mixture of [7-3H]20a-hydroxycholesterol and [4-1 ^cholesterol (3H/I4C ratio 8.68) to a Digitalis lanata plant. The in vivo transformation of the administered steroids to cardenolides was observed. In addition, [7-^progesterone totally devoid of 14C was isolated. The varia-T Ahe biosynthesis of cholesterol from mevalonic acid in Digitalis purpurea (Jacobsen and Frey, 1967) has been demonstrated. The metabolism of cholesterol to pregnenolone (II) (Chart I) (Caspi et al., 1966) and the incorporation of the latter to cardenolides has been proved (Tschesche and Lilienweiss, 1964; Tschesche and Brassat, 1966;Caspi and Lewis, 1967). Subsequently, the conversion of pregnenolone (II) into progesterone (III) (Caspi and Lewis, 1967) and of the latter into cardenolides was demonstrated in Digitalis lanata (Caspi and Lewis, 1967; Bennet et al., 1968). The sequence of steps from pregnenolone to the C23 products requires the intermediacy of a 3-ketone, presumably of progesterone (Caspi and Hornby, 1968).The degradation of the C2? precursor to C21 intermediates in the plant has been considered to be analogous to that incident in animals (Heftmann, 1967;Frantz and Schroepfer, 1967). Consequently, the sequence cholesterol -* 20a-hydroxycholesterol (I) -pregnenolone (II) -* progesterone (III) -* cardenolides was implied to be the operating pathway in the biosynthesis of cardiac aglycones. The present work was undertaken with a view to examine the validity of this assumption.The rationale of our approach was to administer a mixture of [4-14C]cholesterol and [7-3H]20a-hydroxycholesterol to a D. lanata plant and to evaluate the relative incorporation of the two tracers into cardenolides. Experimental SectionChromatography. Silica gel (Merck HF264) was used for thin-layer chromatography in the indicated solvent

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Whitham and PVickramxbgIzc. 1665 326. Xolvolysis of the Toluene-p-sulphoiaates of 39 -and 3a -H ydroxymethyl -A-norcholest -5-ene.By G. H. WHITHAM and (in part) J. A. F. WICKRAMASINGHE.Solvolysis of the toluene-p-sulphonate of 3P-hydroxymethyl-~-norcholest-5-ene gives the same alcohols, in the same proportions, as those obtained from cholesteryl toluene-P-sulphonate. I n contrast, the toluene-P-sulphonate of 3a-hydroxymethyl-a-norcholest-5-ene affords 3p,5-cyclo-5p-cholestan-6P-01, together with the. parent alcohol. The two A-nor-systems can, therefore, have no cationic intermediates in common. The bearing of these results on the mechanism of the cyclo-sterol rearrangement is discussed.' A CONSIDERABI.E amount of work has been devoted towards an understanding of the processes involved in the conversion of derivatives of cholesterol (I; R = H),* e g . , the toluene-9-sulphonate (I ; R = p-Me*C,H,*SO,), into 3a,5-cyclo-5a-cholestan-6~-ol (11) (the cyclo-sterol rearrangement ,). Strong evidence that the double bond of cholesteryl toluene-9-sulphonate assists in the rate-determining ionisation is provided by the fact that, at 50°, it undergoes acetolysis 120 times faster than 5a-cholestan-3p-yl toluene-$sulphonate. This has been explained in terms of the formation of an intermediate nonclassical cation.7 Thus, the transition state for formation of the intermediate is considered to be stabilised by overlap between the x-orbital of the double bond and the developing vacant orbital at C-3. Two possible non-classical cations have been envisaged, ~~i z . , the " unsymmetrical ion " (111) involving only delocalisation of the x-electrons of the double bond, and the " symmetrical ion " (IV) which implies additional delocalisation of the 6-electrons of the C-4-C-5 bond., In an attempt to decide between these two possibilities, and to gain further information about related cationic intermediates, we investigated the solvolyses of the toluene-9-sulphonates of the epimeric A-nor-alcohols (V) and (VI) .3~-Hydroxymethyl-~-norcholest-5-ene (V) is not described in the literature, and was synthesised as follows. Hydroxylation of cholest-4-ene with osmium tetroxide gave a mixture of two glycols (VII) ; the major isomer is presumably 5a-cholestane-4a-,6a-diol and the minor one 5P-cholestane-4p,5p-diol, though no attempt was made to verify these assignments. Cleavage of either glycol with lead tetra-acetate gave the keto-aldehyde (VIII), which was cyclised directly to the unsaturated aldehyde (IX) using hydrochloric * Three-dimensional formula? will be used where necessary, t o avoid the designation of ct-bonds with dotted lines. Dotted lines will be reserved t o indicate partial bonds in non-classical intermediates and transition states.t There seem t o be no steric ambiguities of the type discussed by H. C. Brown in this system, so that replacement of the non-classical cation by an equilibrating set of classical ions would render it very difficult t o understand the rate difference, particularly since the sp3-hybridised C-5 would...