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The overall aim of this investigation was to identify novel bacterial and fungal biocatalytic routes towards monoterpene alcohols such as enantiopure linalool and menthol, and geraniol, each of which find many applications within the flavour and fragrance industries. The first part of the investigation targeted hydrolytic transformations of racemic monoterpene esters. Enantioselective linalyl acetate esterase activity was detected in Rhodococcus ruber DSM 43338, offering a potential route towards enantiopure (R)- and (S)- linalool. Fractions displaying complementary enantioselectivity for the reaction were isolated from anion-exchange chromatography of cell extracts, giving enantiomeric excess values for linalool ranging from 60% (R)- to 79% (S)-. Attempts to isolate the genes encoding relevant esterases via polymerase chain reactions resulted in a gene fragment representing 75% of a putative tertiary alcohol esterase (TAE). An alternative gene putatively encoding a TAB from a closely related Actinomycete Nocardia farcinica (NITAE) was cloned and expressed in E. coli, and the enzyme purified and characterised. NITAE was inactive towards linalyl acetate, but catalysed the hydrolysis of racemic menthyl acetate to give the commercially-preferred 1(R)-enantiomer of menthol. In the second part of the project, a strain of Rhodococcus erythropolis MLTl was isolated by selective enrichment from soil surrounding hop plants using the hop terpene f3-myrcene as sole carbon source. Resting-cell preparations transformed 13- myrcene to the high-value monoterpene alcohol geraniol. While the relevant enzyme remains to be identified, initial studies suggested an inducible operon for f3-myrcene degradation in MLTl.

A review of the biological properties and the synthesis of α-methylene-γ- and -δ-lactones is presented. Cholesterol (201) was converted into 4-oxa-3-oxo-5α-cholestane (203) and the α-methylene moiety was introduced by α-hydroxymethylenation, diethylamination and elimination of diethylamine after hydrogenation to give 2-methylene-4-oxa-3-oxo-5α-cholestane (225). The same sequence of reactions was employed to prepare 17β-hydroxy-2-methylene-4-oxa-3-oxo-5α-androstane (238) and its 17-yl acetate (239) from androst-5-en-3β-ol-17-one (228). Reactions of the above α-methylene lactones with L-cysteine gave the cysteine-lactone adducts in a Michael-type addition. Reaction of the lactone (203) with phenyl magnesium bromide gave 4-oxa-3-phenyl-5α-cholest-2-ene (278). On epoxidation this compound gave an unusual rearranged product. 3-hydroxy-4-oxa-3-phenyl-5α-cholestan-2-one (281) which on treatment with ethanol/hydrochloric acid formed 3-ethoxy-4-oxa-3-phenyl-5α-cholestan-2-one (282). Oxidation of the rearranged product (281) with lead tetra acetate gave 5-benzoyloxy-2,3-seco-5α-cholestan-2-oic acid (299) which on esterification gave the methyl ester (300). The oxidised product (299). after hydrolysis. was cyclised to give A-nor-3-oxa-5α-cholestan-2-one (274).

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There has been considerable interest in the synthesis and biological properties of sesquiterpene lactones as a result of their cytotoxic activity. This manuscript describes a concise synthesis of the elemanolide model compound 3.1 and studies towards the synthesis of 8-deoxyvernolepin 1.6. The first chapter will deal with sesquiterpene motifs, culminating in the introduction of elemanolides and eudesmanolides. Isolation and biological activity of elemanolides (particularly vernolepin) will be presented, along with a possible biosynthesis and selected previous syntheses. Chapter two details the role of manganese triacetate in oxidative radical reactions, highlighting the main differences between manganese and tin. A brief outline of work done in our group on oxidative cyclisations with manganese(III) acetate is included, along with examples of tethered cyclisations. Chapter three discusses an enantioselective route to a model compound of 8-deoxyvernolepin 1.6 utilising an enantioselective Diels Alder reaction, followed by attempted 1,3-transpositons of stereochemical information. Chapter four describes a racemic synthetic pathway to both 8-deoxyvernolepin 1.6, the model compound 3.1 and subsequent analogues, using a racemic Diels-Alder reaction, palladium-mediated π-allyl substitution and tin-mediated radical substitution.