Navigating the Chiral Pool in the Total Synthesis of Complex Terpene Natural Products

Abstract

The pool of abundant chiral terpene building blocks (i.e. “chiral pool terpenes”) has long served as a starting point for the chemical synthesis of complex natural products, including many terpenes themselves. As inexpensive and versatile starting materials, such compounds continue to influence modern synthetic chemistry. This review highlights 21st century terpene total syntheses which themselves use small, terpene-derived materials as building blocks. An outlook to the future of research in this area is highlighted as well.

Diterpene Synthase‐Catalyzed Biosynthesis of Distinct Clerodane Stereoisomers

“…These mechanistically related enzymes facilitate the protonation‐initiated cyclization and rearrangement of the central ( E,E,E )‐geranylgeranyl diphosphate (GGPP) precursor to form different bicyclic prenyl diphosphates . Enzymatic control over the distinct configuration and oxygenation of these pathway intermediates is critical for downstream functional decorations and diterpenoid bioactivity . Class II diTPS‐catalyzed reactions typically proceed via a common labda‐13 E ‐en‐8‐yl + diphosphate intermediate with a trans ‐decalin bridgehead and distinct absolute stereochemistry, likely defined by precatalysis folding of GGPP into a specific prochiral conformation .…”

Convenient Access to Chiral Cyclobutanes with Three Contiguous Stereocenters from Verbenone by Directed C(sp3)−H arylation

“…In light of the diminishing supplies of fossil‐based feedstocks and the negative environmental impact associated with their use, there exists a growing interest for chemical processes that can enable access to value‐added products from renewable sources . Here, the terpenes constitute a particularly well‐utilized class of natural products, which has found extensive use in the manufacturing of a wide range of valuable chemical products such as fuels, fragrances,, pharmaceuticals,, and polymers, as well as different kinds of reagents and catalysts …”

Stereodivergent Synthesis of Carveol and Dihydrocarveol through Ketoreductases/Ene‐Reductases Catalyzed Asymmetric Reduction

“…Meanwhile, most stereoisomers of carveol, dihydrocarvone, and dihydrocarveol are not commercial available now. Since different stereoisomers of these compounds have distinct odor quality/intensity and biological effects, and also can be used as starting materials for synthesis of different bioactive natural products, generation every possible stereoisomer of these compounds through stereodivergent synthesis is therefore highly desired.…”