Untersuchungen zur Biogenese der Indolalkaloide. Synthese und Verfütterung radioaktiv markierter Hydroxyloganin‐Derivate ¹⁾

Abstract

Zur Prufung der Moglichkeit, o b Hydroxyloganin (4a) oder dEpihydroxyloganin (5a) Zwischenrtufen in der Biogenese von Secologanin (2a) und der Indolalkaloide sind, wurden beide Verbindungen in radioaktiv markierter Form hergestellt. D a m reduzierte man die Ketocarbonsaure 6 mit ['H]Natriumborhydrid und veresterte die Hydroxycarbonsauren 9* bzw. 11 mit ["CIDiazomethan. Futterungsversuche rnit Catharanthus roseus G. Don ergaben, dan 4 a und 5a mit groner Wahrscheinlichkeit keine Vorstufen von 2a und der Indolalkaloide sind. Durch Isolierungsversuche wurde aunerdem gezeigt, da8 4 a kein naturlich vorkommendes lridoidglycosid in Menyanthes trifoliata ist . Investigations of the Biosynthesis of Indole Alkaloids. Feeding Experiments with Synthetic Radioactively Labelled Hydroxyloganin Derivatives l)Hydroxyloganin (4a) and 6-epihydroxyloganin (5a) were synthesized with a radioactive label to check the hypothesis that these compounds lie directly on the biosynthetic pathways to secologanin (2a) and the indole alkaloids. The labels were introduced by reduction of the keto acid 6 with sodium ['Hlborohydride and esterification of the hydroxy acids 9* or 11 with ['4C]diazomethane. According to feeding experiments with Calharanthus ro.seus G. Don it is highly improbable that 4 a and 5 a are precursors of 2a and the indole alkaloids. Moreover, isolation experiments showed that 4s is not a naturally occurring iridoid glycoside in Menyanthes rrijoliata plants.Eine Schlusselreaktion in der Biogenese der Indolalkaloide') und weiterer Naturstoffe 3, ist die Uberfuhrung des Monoterpen-Bausteins Loganin (1) in Secologanin (2a), das dann mit Tryptamin in Art einer Mannich-Reaktion zu Strictosidin (Isovincoside)4) (3), der ersten stickstoffhaltigen Vorstufe der Indolalkaloide, kondensieren kann. Beim Ubergang von 1 in 2a erfolgt Spaltung des Cyclopentanringes unter Bildung einer 6 , E-ungesattigten Aldehydgruppe. Als mogliche Zwischenstufen lassen sich hierbei Hydroxyloganin (4a) 5, und 6-Epihydroxyloganin (5a) formulieren, die durch eine enzymatische Fragmentierung z. B. in Form der Phosphorsaureester 4b und 5b zu 2a gepalten werden konnen 6). So gelang es vor kurzem, das 6-Epihydroxyloganin-Derivat 5c in vitro mit sehr guten Ausbeuten in das Secologanin-Derivat 2b zu iiberfiihren').

Formal Total Synthesis of (±)‐Strictamine by [2,3]‐Sigmatropic Stevens Rearrangements

“…[21] Biosynthetically,s trictamine (1)b elongs to the group of monoterpenoid indole alkaloids, which are derived from (E)-geissoschizine (4). [22][23][24][25][26][27][28][29] In contrastt oo ther monoterpenoid indole alkaloids, the akuammiline alkaloids are defined by one CÀCb ond between carbon atomsC -7 and C-16,l eading to av ery compact cage-like structure (methanoquinolizidine 2)r eminiscento fa damantane (3). In contrastt oa damantane (3), which harbors four six-membered rings in ac hair conformation,t he methanoquinolizidine system 2 consists of two six-membered rings in ab oat conformationa nd only one in ac hair conformation.…”

“…In particular, strictamine ( 1 ) was first synthesized in 2015 and 2016 by the groups of Garg (enantioselective), Zhu (racemic), Ohno (formal), and ours (formal) . Biosynthetically, strictamine ( 1 ) belongs to the group of monoterpenoid indole alkaloids, which are derived from ( E )‐geissoschizine ( 4 ) . In contrast to other monoterpenoid indole alkaloids, the akuammiline alkaloids are defined by one C−C bond between carbon atoms C‐7 and C‐16, leading to a very compact cage‐like structure (methanoquinolizidine 2 ) reminiscent of adamantane ( 3 ).…”

Single electron transfer in reactions of alkyl halides with lithium thiolates

“…For the purpose of examining SET in the formation of substitution products, reactions of thiolates with trityl halides in the presence of the radical trap, DCPH, were also carried out and the results are included in Table II. Indeed in the presence of DCPH, the radical dimer product 4, and the a-substitution product 1 were both diverted to the hydrogen abstraction product 3 (compare experiments 1 vs. 2 and 4 vs. 5).…”

“…» k2) in the reaction of a nucleophile with an alkyl halide involving SET (eq 3), then the intermediate radical species could be detected by spectroscopic methods (EPR and UV). However, for a Nu: + RX [RX--+ Nu-] -j* RNu + X- (3) reaction system where the intermediate radical produced is not stable, the SET step is rate determining (&, « k2) and other methods need to be used to detect the radical intermediate. Among those methods reported to detect unstable radical intermediates, the following have been most often encountered in the literature: (1) use of cyclizable probes,21-24 (2) use of radical traps, [23][24][25][26] (3) use of spin trapping techniques,27,28 and (4) use of a linear freeenergy correlation between the rate constants of the reaction and the reduction potentials of the substrates depending on the nature of the leaving group.…”

“…Among those methods reported to detect unstable radical intermediates, the following have been most often encountered in the literature: (1) use of cyclizable probes,21-24 (2) use of radical traps, [23][24][25][26] (3) use of spin trapping techniques,27,28 and (4) use of a linear freeenergy correlation between the rate constants of the reaction and the reduction potentials of the substrates depending on the nature of the leaving group. [29][30][31] In the present study concerning the reactions of thiolates with alkyl halides we report the results of (1) the use of cyclizable probes to detect radical intermediates, (2) direct spectroscopic (EPR) observation of the trityl radical in reactions of thiolates with trityl halides, (3) product distribution studies in the reactions of thiolates with 2,2dimethyl-l-iodo-5-hexene, (4) studies on the effect of DCPH as a radical trapping agent, and (5) evaluation of thiolate anions as one-electron donors toward various organic substrates such as diaryl ketones, polynuclear hydrocarbons, and 9-bromofluorene (all well-known oneelectron acceptors).32 (15) Kornblum, N. Angew. Chem., Int.…”