Approach to the Biosynthesis of Atisine-Type Diterpenoid Alkaloids

Abstract

To determine the biosynthesis pathway of the atisine-type diterpenoid alkaloids spiramines A/B and C/D, feeding experiments in in vitro cultured plantlets and enzymatic transformations in cell-free extracts were performed in combination with LCMS and tandem MS analyses. L-[2-(13)C,(15)N]Serine was used in the feeding experiments and enzymatic transformations, and the diterpene spiraminol was identified as a biosynthetic precursor of spiramine alkaloids. The LCMS and tandem MS spectra of the extracts from these experiments indicated that L-[2-(13)C,(15)N]serine was incorporated into spiramines A/B and C/D. The labeled reaction products show that l-serine is the one possible nitrogen source involved in the biosynthesis of atisine-type DAs.

Studies towards Bioinspired Synthesis of Hetidine‐Type C20‐Diterpenoid Alkaloids

“…[15] Having secured the ajaconine core structure (28), we then turned our attention to the synthesis of hetidine-type skeleton via an aza-Prins cyclization (Scheme 7). Treatment of aminal 28 with NaOAc/HOAc at 80 ℃ afforded an interesting product (44, 68% yield), [16] in the NMR spectra of which both the  13,14 and  [17] Given that diterpenoid alkaloids were supposed to be biogenetically derived from related diterpenes, [2,18] identification of 44 and 45 may indicate a latent structural type of diterpenoid alkaloids which has not yet been discovered from nature. To the best of our knowledge, our efforts have provided the first access to such rigid systems by chemical synthesis.…”

Terpenoid‐Alkaloids: Their Biosynthetic Twist of Fate and Total Synthesis

“…While the biosynthesis of these diterpenoids is generally understood, specific details of the biosynthetic processes are still unclear. 1,45 Most recently, Tantillo and co-workers proposed a biosynthetic hypothesis that did not invoke secondary carbocations (Fig. 4a).…”

“…These hydrocarbon skeletons are then oxidized and a nitrogen atom derived from L-serine is incorporated into the molecule in the form of β-aminoethanol 45a to subsequently form a piperidine ring. In the kaurane ( 87 ) series, this forms the skeleton of veatchine-type C 20 terpenoid-alkaloids ( 88 ), and in the atisane ( 89 ) series the atisine-type skeleton ( 90 ) is formed.…”

“…Aconite alkaloids are notorious, covert human poisons, however, other C 19 -diterpenoid alkaloids possess analgesic, anesthetic, antiarrhythmic, antifibrillatory, and anti-inflammatory properties, as well as the ability to repel insects. 45b Like lappaconitine, some can counter the arrhythmic effects of aconitine poisoning and this has prevented death in animals poisoned with lethal doses of aconitine. 51,52 So far, only the work of Wiesner has resulted in the successful total syntheses of several C 19 -diterpenoid alkaloids possessing a variety of skeletons.…”

First total synthesis of concavine

“…This type of biosynthetic genesis has been explored in more detail for the related atisine-type alkaloids. 2 Concavine features a tetracyclic core structure that incorporates a bicyclo[3.2.1]octane motif fused to a pyrrolo-oxazepane, and this unique polycyclic array, including the presence of five stereogenic centres, make concavine an interesting synthetic prospect. 3 …”