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A series of reactions of podocarpic acid has been investigated. These include the preparation and ozonolysis of some podocarpa-8,11,13-6β,19-olides, the diborane-boron trifluoride reduction of the 7-keto and the 6β,19-lactone groups of 12-methoxy-7-oxypodocarpa-8,11,13-trien-6β,19-olide (21), and the addition of bromine azide to some 12-methoxypodocarpa-6,8,11,13-tetraene derivatives which gave products of unexpected stereochemistry. Ozonolysis of podocarpic acid gave the 8α,12-lactone of 8β-hydroperoxy-(13-17)-pentanorlabdan-19-oic acid (82) which was reduced to the hydroxy-lactone (83) and the keto-diacid (84). The esters (81) and (87) of compounds (83) and (84) were prepared and used as model compounds for the attempted synthesis of the fungicide LL-21271α. An efficient method for generating an exocyclic methylene group at C-8 of the (13-17)-pentanorlabdane skeleton was found, and the preparation and some reactions of the epoxides of dimethyl (13-17)-pentanorlabd-8(17)-en-12,19-dioate (130) and dimethyl (13-17)-pentanorlabd-8(9)-en-12,19-dioate (133) have been investigated. Bromination of 8-oxo-(13-17)-pentanorlabdan-dioic acid esters gave unexpected 7α-bromo derivatives. Methyl, hydrogen 7α-bromo-8-oxo-(13-l7)-pentanorlabdan-12,l9-dioate (162) was found to undergo an unusual elimination and decarboxylation reaction to give the methylene ketone (166) which underwent dimerisation affording compound (167). Some C-19 oxygenated compounds that were expected to have ambergris-type odours were prepared and found to be odourless. An improved method of reduction of methyl-12-methoxy-7-oxopodocarpa-5,8,11,13-tetraen-19oate (199) to 12-methoxypodocarpa-5,8,11,13-tetraen-19-ol (201) was found and the mechanism was studied. A series of C-19 methyl ethers of podocarpic acid derivatives was prepared in order to elucidate the above reduction mechanism. Also investigated were the functionalisation of the C-10 axial methyl group of podocarpic acid via photolysis of the 6β-nitrite ester for the preparation of 12-methoxy-19-norpodocarpa-3,5,8,11,13-tetraen-7-one (237), and the photo-oxygenation of 12-methoxy podocarpa-6,8,11,13-tetraen-19-oic acid (57) to give a 4-hydroperoxide (240) which was subsequently reduced to 12-methoxy podocarpa-4,8,11,13-tetraen-7-one (243).

PART ONE SYNTHESIS AND ACID-CATALYSED REARRANGEMENT OF CYCLOPROPANE-1,2-DIOLS A number of cyclopropane-1,2-diyl diacetates have been synthesized by the anhydrous Clemmensen reduction [Zn(Hg)-HCl-organic solvent] of β-diketones and β-ketoaldehydes, and this reaction was found to be a general one for those substrates that did not exist mainly in the enol form. Cyclopropanediol formation does occur with some highly enolized compounds under aqueous conditions but, with the anhydrous system, enol acetate formation or enolic reduction was found to compete with reduction of the diketo form. Acid-catalysed rearrangement of the free diols generally gave α-hydroxy-ketones, or their corresponding αβ-unsaturated enones, with β-hydroxy-ketone formation only being observed with one substrate. A strong preference for methyl ketone formation was observed in all cases and this phenomenon was rationalized by consideration of the apparent relative thermodynamic stabilities of the α-ketol conjugate acids. PART TWO AROMATIZATION OF 2α-HYDROXY[4-13C]CHOLEST-4-EN-3-ONE The aromatization of 2α-hydroxy[4-13C]cholest-4-en-3-one has been found to occur with migration of the labelled carbon to C-10, thereby lending support to previous mechanistic proposals. The aromatization of [4-13C]cholesta-1,4-dien-3-one similarly gave a product with the label at C-10, in agreement with earlier work involving carbon-14 labelling studies. The ease with which these rearrangements could be studied is in marked contrast to earlier work, and the combination of carbon-13 labelling and 13C n.m.r. spectroscopy offers many advantages over the degradative techniques required with carbon-14 labelling. PART THREE CLEMMENSEN REDUCTION OF (5R)-5-HYDROXYHEXAN-2-ONE Previous work in this department suggested that the Clemmensen reduction of γ-substituted ketones involved an intramolecular displacement of the γ-substituent by the carbonyl oxygen atom. However, the reduction of (5R)-5-hydroxyhexan-2-one had given a mixture of hexan-2-ol and cis- and trans-hex-4-en-2-ol, with no inversion of stereochemistry occurring with the saturated isomer. The opposite signs of rotation for the two geometrically isomeric alkenols suggested the possibility of different chiralities, but this was disproved when the 2R-configuration was determined for each alcohol by analysis of the 1H n.m.r. spectra of the esters with (-)-(S)-α-methoxy-α-trifluoromethyl-phenylacetic acid. This result thus invalidates the earlier hypothesis.