Synthetic and Configurational Studies of Biosynthetic Precursors

A synthesis of 7-14C-shikimic acid was attempted. It was hoped to decarboxylate the closely related quinic acid to yield a 3:4:5-trihydroxy-cyclohexanone. Suitable recarboxylation of such a derivative using labelled reagents would yield a product which on dehydration and hydrolysis would provide 7-14C-shikimic acid. It was not found possible to repeat a Hunsdieker reaction on the silver salt of tetra-acetyl quinic acid which had previously been described as resulting in 3:4:5-triacetoxy-cyclohexanone. The two known modifications of 3:4-isopropylidene-3:4:5-trihydroxy-cyclohexanone were prepared and, contrary to the claims in the literature, found to be two crystalline modifications of the same free ketone. A number of cyanohydrin reactions were attempted on this ketone and its acetyl derivative without success. Ethynylation of these ketones also failed. When an attempt was made to form the pyrrolidine enamines of the ketones the product isolated was found to be N-(p-hydroxyphenyl)-pyrrolidine. Acetic anhydride dehydration of tetra-acetyl-quinamide and of 3-acetyl-4:5-isopropylidene-quinamide yielded the respective acetyl cyanohydrins as described in the literature. An alternative route to 3:4:5-triacetoxy-cyclohexanone was successfully repeated. This involved the lead tetra-acetate cleavage of 3:4:5-triacetyl china alcohol. There was unfortunately no time available to undertake recarboxylation of this ketone, either by the previously reported cyanohydrin reaction or otherwise. It was decided to obtain derivatives of geraniol and nerol suitable for x-ray analysis in order to establish the respective configurations of the alcohols beyond doubt. The p-iodobenzoates and p-bromobenzoates of the alcohols were prepared and found to be liquids. p-(p-Bromophenylazo)-benzoic acid was prepared by coupling p-bromo-nitrosobenzene with p-aminobenzoic acid. Reaction of geraniol and nerol with the acid chloride gave the esters. These esters were submitted for x-ray analysis as crystalline solids. As a check against isomerisation the esters of a-terpineol and citronellol were also prepared. The proton magnetic resonance spectra of all the compounds prepared were analysed