Über 1,3‐Hydridverschiebungen in Sesquiterpen‐Cyclisierungen

Abstract

Stereospezifischm arkierte Vorstufen wurden mit sieben bakteriellen Sesquiterpencyclasen konvertiert, um den stereochemischenV erlauf ihrer initialen Kaskaden aus 1,10-Cyclisierung und 1,3-Hydridverschiebung zu untersuchen. Enzyme mit Produkten bekannter absoluter Konfiguration zeigten einen kohärenten stereochemischen Kurs,m it Ausnahme der (À)-a-Amorphen-Synthase,f ürd ie die erhaltenen Ergebnisse besser durch initiale 1,6-Cyclisierung erklärbar sind. Der Zusammenhang zwischen der absoluten Konfiguration des Produktes und dem stereochemischen Verlauf der 1,3-Hydridverschiebung ermçglichte die Zuordnung der absoluten Konfigurationen fürd rei Enzymprodukte,d ie unabhängig über die absolute Konfiguration des gemeinsamen Nebenproduktes Germacren-D-4-ol bestimmt wurden. ickschat NederlandsI nstituut voor Ecologie Koninklijke Nederlandse Akademie van Wetenschappen Droevendaalsesteeg 10, 6708 PB Wageningen (Niederlande) Hintergrundinformationen und die Identifikationsnummer (ORCID) eines Autors sind unter http://dx.doi.org/10.1002/ange.201608042 zu finden. Schema 1. A) Initiale 1,10-Cyclisierungvon FPP über (S)-oder (R)-NPP zu Kation 5.Dessen absolute Konfiguration ist mit den (in 2)enantiotopen Wasserstoffen verknüpft, von denen nur eines stereospezifisch eine 1,3-Verschiebung eingeht. Dabei wandert H S im Fall von (R)-5 wohingegen H R fürdie Reaktion zu (S)-5 springt. B) Reaktionen von 5 zu Cadalanen und zu Germacren-D-4-ol.

Enzymatic Synthesis of Methylated Terpene Analogues Using the Plasticity of Bacterial Terpene Synthases

“…The installation of the stereocentre at C7 in A is explained by FPP isomerisation through syn ‐allylic transposition to ( R )‐NPP and anti ‐S N 2’ attack with 1 Re ,10 Re cyclisation, with a defined stereochemical course for the enantiotopic C1 hydrogens of FPP. As a consequence, the 1‐ pro ‐ S hydrogen of FPP selectively migrates into the i Pr group of B , as demonstrated experimentally by enantioselective deuteration of FPP …”

Mechanisms of the Diterpene Cyclases β‐Pinacene Synthase from Dictyostelium discoideum and Hydropyrene Synthase from Streptomyces clavuligerus

“…However, the labelled monomer (2‐ 2 H)dimethylallyl PP (DMAPP) is easier accessible by synthesis (Scheme S1 in the Supporting Information) and was used for the elongation to (14‐ 2 H)GGPP with isopentenyl PP (IPP) through the FPP synthase (FPPS) from Streptomyces coelicolor and the GGPP synthase (GGPPS) from S. cyaneofuscatus (note that the combination of FPPS and GGPPS is more effective than GGPPS alone) . The subsequent cyclisation by PcS yielded a product with retained deuterium that could be located in the i Pr group by inspection of the EI‐MS (electron impact) fragmentation pattern (Figure S11), in agreement with the 1,2‐hydride shift from A to B . The conversion of both ( R )‐ and ( S )‐(1– 2 H)GGPP revealed the specific loss of H1 R and retainment of H1 S in the final deprotonation step (Figure S11).…”

“…The absolute configuration of a terpene can be deduced from enantioselectively deuterated precursors by incorporation of labelling into one of two diastereotopic positions, if the stereocentre at the deuterated carbon remains unchanged (or is changed with a known course) during terpene biosynthesis, because the configurations of all other stereogenic centres in the product can be inferred from their relative orientation to this stereogenic centre . Using this approach, the absolute configurations of 3 , 4 and 5 were delineated from incubations of ( R )‐ and ( S )‐(1‐ 13 C,1‐ 2 H)FPP with IPP, GGPPS and HpS (Figure S32–S34), which resulted in the absolute configurations for 2 , 3 , 4 and 5 as in Scheme .…”

Mechanistic Studies on Trichoacorenol Synthase from Amycolatopsis benzoatilytica

“…Therefore, unambiguous identification was achieved by analysis of the products obtained from an incubation of TaS with (1,1‐ 2 H 2 )FPP (Figure S13), in which two deuterium atoms were retained for 3 , but only one for 4 . The stereochemical courses for the elimination reactions were found to predominantly proceed through 1,2‐ syn elimination for 3 and 1,4‐ syn elimination for 4 , as followed by incubations of TaS with ( R )‐ and ( S )‐(1‐ 2 H)GPP, IPP and FPPS, or ( R )‐ and ( S )‐(1‐ 2 H)FPP, respectively (Figure S14). In cases of deuterium abstraction, a decreased stereoselectivity for these processes was observed.…”