No abstract

This review describes applications of quantum chemical calculations in the field of terpene biosynthesis, with a focus on insights into the mechanisms of terpene-forming carbocation rearrangements arising from theoretical studies.

Aquatolide has been reisolated from its natural source, and its structure has been revised on the basis of quantum-chemical NMR calculations, extensive experimental NMR analysis, and crystallography.

In this tutorial review, structures encountered in carbocation cascade polycyclization reactions leading to terpene natural products are surveyed. The nature of delocalization in these carbocations is discussed in detail. For select cases, the ability of functional groups in enzyme active sites to modulate this delocalization is discussed. In addition to carbocation intermediates, cationic transition state structures are also described.

Quantum chemical calculations on cyclization mechanisms for several sesquiterpene families proposed to be closely related to each other in a biogenic sense (the bisabolene, curcumene, acoradiene, zizaene (zizaene, isozizaene, epi-zizaene, and epi-isozizaene), cedrene (alpha/beta-cedrenes and 7-epi-alpha/beta-cedrenes), duprezianene, and sesquithuriferol families) are described. On the basis of the results of these calculations, we suggest that the conformation of the bisabolyl cation attainable in an enzyme active site is a primary determinant of the structure and relative stereochemistry of the sesquiterpenes formed. We also suggest that substantial conformational changes of initially formed conformers of the bisabolyl cation are necessary in order to form zizaene and epi-cedrene. Given that the productive conformation of the bisabolyl cation does not necessarily reflect the original orientation of farnesyl diphosphate bound in the corresponding enzyme active site, we conclude that folding of farnesyl diphosphate alone does not always dictate the structure and relative stereochemistry of cyclization products. In addition, the potential roles of dynamic matching in determining product distributions and enzyme-promoted formation of secondary carbocations are discussed.