Modern Aspects of Isotopic Labellings in Terpene Biosynthesis

Abstract

In this review article recent isotopic labelling experiments are presented that served in the elucidation of the complex mechanisms of terpene biosynthesis. The article is structured by first presenting the recent advances in the biosynthesis of terpene monomers, followed by sections on monoterpenes, sesquiterpenes and diterpenes. This overview covers a personal selection of eminent examples from the accumulated literature since 2010.

Bacterial Diterpene Biosynthesis

“…Our understanding of their enzyme mechanisms was significantly improved by isotopic labelling experiments that were classically performed by feeding labelled precursors to actively growing cultures,b ut are especially powerful with defined substrates in in vitro incubations with purified recombinant enzymes. [70,71] The recently obtained crystal structures of diterpene synthases also gave important insights and allowed for site-directed mutagenesis approaches. [4] Finally,q uantum mechanical calculations can make important contributions,a st he cationic intermediates in terpene cyclisations are not directly observable.…”

Computational and Synthetic Investigation of Cationic Rearrangement in the Putative Biosynthesis of Justicane Triterpenoids

“…A kinetic isotope effect (KIE) experiment was designed which required a C1-deuterated decalin precursor. [21] Substrate 7-D was prepared, with deuterium incorporation at C1 and C3, and mixtures of 7 and 7-D were subjected to rearrangement reaction conditions in a one-pot competition experiment (Figure 2A). The dideuterated substrate was used to simplify spectroscopic analysis (see Supporting Information), and it is not expected that deuteration at C3 would significantly impact the value of the KIE.…”

Catalytic Generation and Chemoselective Transfer of Nucleophilic Hydrides from Dihydrogen

“…Although these results showed the feasibility of using H 2 as a hydride source in a catalytic hydride‐transfer reaction, one additional advantage of the current approach is that, upon switching to deuterium gas (D 2 ), selective monodeuteration in the allylic position could be achieved, which leads to valuable deuterated products. Selective isotope labeling is a key technology for drug discovery and the elucidation of reaction mechanisms or biosynthetic pathways . In this regard, we could show that a catalytic method for regio‐ and chemoselective monodeuteration employing D 2 is viable (Scheme ).…”

“…Selective isotope labeling is ak ey technology for drug discovery [19] and the elucidation of reaction mechanisms [20] or biosynthetic pathways. [21] In this regard, we could show that ac atalytic method for regio-and chemoselective monodeuteration employing D 2 is viable (Scheme 2). When cinnamyl chloride (Z-2)w as subjected to the allylic reductionc onditions with D 2 ,w ef ound that the conversion dropped to 68 %( indicating ak inetic isotope effect)w ith improvedr egioselectivity (3-d 1 /4-d 1 = 95:4), and excellent isotope incorporation (> 95 %Dof 3-d 1 ).…”