The biosynthesis of tigliane and related diterpenoids; an intriguing problem

The biosynthesis of tigliane and related diterpenoids; an intriguing problem. An hypothesis to explain the relationships between various diterpenoids found in members of the Euphorbiaceae is proposed. The likely nature of the tetraprenyl pyrophosphate precursor is considered, as is the manner in which the precursor may cyclize. It is thought that up to eight possible precursors may exist, being the various cisjtrans isomers of geranyl-geranyl pyrophosphate. This suggestion arises from an acceptance of the now well-established (but as yet unproven) process of an initial head-to-taiF cyclization of the precursor to form the variously cyclized hydrocarbon skeletons of tigliane and related diterpenoids. It is considered that the necessary isomerization of up to three of the prenyl units, as would have to be the case if the tigliane skeleton were produced from the all-trans geranyl-geranyl pyrophosphate, is not reconcilable with an initial head-to-tail cyclization of the precursor either on the grounds of spatial considerations or on the evidence of the currently known chemical variation in the whole family of compounds.