Mevalonic acid stereospecifically labelled with tritium in the 2-position was incubated, in a deuterium oxide medium containing adenosine triphosphate, with a soluble enzyme preparation from pig liver; and so converted into farnesyl pyrophosphate. This was hydrolysed enzymically to farnesol which was oxidized, by ozone followed by sodium hypoiodite, to acetic acid originating from the terminal isopropylidene group of farnesol. The tritium in this acetic acid was found, on analysis by a recently developed enzymic method, to be present largely in chiral methyl groups the chirality of which was
R
or
S
according to the chirality at C-2 of the parent mevalonic acid. It is deduced that these chiral methyl groups were formed on the enzyme isopentenyl pyrophosphate isomerase, by addition of a deuteron from the medium to the 3
re
, 4
re
face of the double bond in isopentenyl pyrophosphate. The stereochemical relationship between the added and abstracted hydrogen in the prototropic isomerization mediated by this enzyme is thereby established. A preliminary communication of these results has been made (Clifford, Cornforth, Mallaby & Phillips 1971).
Base-catalyzed 1-3 Prototropic Isomerization of Cycloheptatrienes
