New Diterpenoid Alkaloids from Spiraea fritschiana var. parvifolia

Two new C20 hetisine-type diterpenoid alkaloids, spirafine III (1) and spirafine II (2), were isolated from the roots of Spiraea fritschiana var, parvifolia. Their structures were elucidated based on HRMS: IR and NMR spectral data, and chemical reaction.

New Diterpenoid Alkaloids from the Roots of Aconitum excelsum Reichb

Two new diterpenoid alkaloids have been isolated from roots of Aconitum excelsum Reichb. These new compounds were named excecoitine I and exceconidine II. The two structures were elucidated by spectroscopic methods as well as comparison with known compounds.

New Diterpenoid Alkaloids from Spiraea japonica var. Ovalifolia

Five new diterpenoid alkaloids. 19-O-deethlyspiramine N (1), deacetylspiramine S (2), spiramidine A (3), spiramidine B (4) and deacetylspiramine F (5) were isolated from the aerial parts of Spirae japonica L. f. var ovalifolia. Their structures were charaterized mainly based on spectral analysis.

Two new C_(19)-diterpenoid alkaloids from roots Aconitum hemsleyanium var. atropurpureum

A new franchetine-type C19-diterpenoid alkaloid 3-hydroxyfranchetine 1 and a new aconitine-type C19-diterpenoid alkaloid atropurpursine 2 have been isolated from the roots of Aconitum hemsleyanium var. atropurpureum. The structures of these new alkaloids were established on the basis of spectral data.

Two New C_(19)-Diterpenoid Alkaloids from Delphinium davidii Franch

Two new C19-diterpenoid alkaloids, davidisines A （1） and B （2） along with thirteen known alkaloids were isolated from the whole herb of Delphinium davidii Franch. Their structures were established by spectral methods, especially 2D NMR techniques.

Two novel aconane-type diterpenes derived from C-nor-C_(19)-diterpenoid alkaloid

Two novel C-nor-B-homo aconane-type diterpenes 4 and 5, featuring a unique eight-membered ring system, were obtained by the treatment of C-nor-C19-diterpenoid alkaloid 3 with HNO2 in 8% and 21% yields, respectively. Structures of these two compounds were established based on the combination of spectroscopic data, including HRESIMS, 1D and 2D NMR data. A olausible mechanism for the formation of 4 and 5 is also presented.

Diterpenoid Alkaloids from the Aerial Parts of Aconitum flavum Hand.-Mazz

Sixteen diterpenoid alkaloids(DAs),including six aconitine-type alkaloids(5 and 9−13),seven 7,17-seco-aconitine-type alkaloids(1−4,6−8),two napelline-type alkaloids(14 and 15)as well as one veatchine-type alkaloid(16),were isolated from the aerial parts of Aconitum flavum Hand.-Mazz.In which,flavumolines A−D(1−4)were four new ones,and flavu-moline E(5)was reported as natural compound for the first time.Their chemical structures were elucidated by the analysis of extensive spectroscopic data.The inhibitory activities of these isolates on Cav3.1 low voltage-gated Ca^(2+)channel,NO production in LPS-activated RAW264.7cells,five human tumor cell lines,as well as acetylcholinesterase(AChE)were tested.

Three new C_(20)-diterpenoid alkaloids from Delphinium anthriscifolium var.savatieri

Three new C20-diterpenoid alkaloids, designated as anthriscifolmines A-C （1-3）, together with two known alkaloids denudatine and delgramine, were isolated from the whole herb of Delphinium anthriscifolium var. savatieri. The structures of these new alkaloids were elucidated on the basis of spectral data.

PREPARATION AND MECHANISM OF 7,17-SECO C_(19)-DITERPENOID ALKALOIDS VIA PYROLYSIS OF THEIR N-OXIDES IN DIGLYME

A new preparation method of the N-ethyl 7,17-seco C_(19)-diterpenoid alkaloids(5)and(6)by pyrolysis of the N-oxides(3)and(4),respectively, in anhydrous diglyme is described.A probable reaction mechanism for the pyroly- sis is presented and studied preliminarily.

Diterpenoid Alkaloids from Delphinium Tongolense

The phytochemical investigation of Delphinium tongolense Franch. yielded two new diterpenoid alkaloids tongolenine C and tongolenine D. Their structures were elucidated by spectroscopical methods.

Three new C_(19)-diterpenoid alkaloids from Delphinium laxicymosum var. pilostachyum

Three new lycoctonine-type C19-diterpenoid alkaloids, laxicymine 1, laxicymisine 2, and laxicyminine 3 have been isolated from the whole herb of Delphinium laxicymosum var. pilostachyum W.T. Wang. Their structures were established by spectra data.

Multi-omics analysis reveals the evolutionary origin of diterpenoid alkaloid biosynthesis pathways in Aconitum

Diterpenoid alkaloids(DAs) have been often utilized in clinical practice due to their analgesic and anti-infammatory properties. Natural DAs are prevalent in the family Ranunculaceae, notably in the Aconitum genus. Nevertheless, the evolutionary origin of the biosynthesis pathway responsible for DA production remains unknown.In this study, we successfully assembled a highquality, pseudochromosome-level genome of the DA-rich species Aconitum vilmorinianum(A.vilmorinianum)(5.76 Gb). An A. vilmorinianumspecific whole-genome duplication event was discovered using comparative genomic analysis,which may aid in the evolution of the DA biosynthesis pathway. We identified several genes involved in DA biosynthesis via integrated genomic, transcriptomic, and metabolomic analyses. These genes included enzymes encoding target ent-kaurene oxidases and aminotransferases, which facilitated the activation of diterpenes and insertion of nitrogen atoms into diterpene skeletons, thereby mediating the transformation of diterpenes into DAs. The divergence periods of these genes in A. vilmorinianum were further assessed, and it was shown that two major types of genes were involved in the establishment of the DA biosynthesis pathway. Our integrated analysis offers fresh insights into the evolutionary origin of DAs in A.vilmorinianum as well as suggestions for engineering the biosynthetic pathways to obtain desired DAs.

Napelline-type C_(20)-diterpenoid alkaloid iminiums from an aqueous extract of ‘‘fu zi'': Solvent-/base-/acid-dependent transformation and equilibration between alcohol iminium and aza acetal forms

Three new napelline-type C20-diterpenoid alkaloids,named aconicarmichinium A and B trifluoroacetates（1 and 2） and aconicarmichinium C chloride（3）,were isolated from an aqueous extract of ＂fu zi＂,the lateral roots of Aconitum carmichaelii.Their structures were elucidated by extensive spectroscopic data analysis.Compounds 1-3 represent the first examples of napelline-type C20 diterpenoid alkaloid alcohol iminiums,of which the structures were fully characterized.In addition,transformation and equilibration between the alcohol iminiums（1-3） and the aza acetals la-3a were investigated by measurements of the NMR spectra in protic and aprotic deuterium solvents including alkali pyridine-d5,along with evaporation under reduced pressure and gradual additions of TFA,AcOH,and HC1.The results demonstrated that the transformation and equilibration were solvent-,base-,and acid-dependent.Especially,in aqueous biological fluid,these C20-diterpenoid alkaloids would more likely exist as the alcohol iminiums accompanied by anion counterparts in biosystems to increase their solubility, bioavailability, transportations, and functions.The absolute configurations of 1-3 were confirmed by X-ray crystallographic analysis of 2a.

Functional identification of the terpene synthase family involved in diterpenoid alkaloids biosynthesis in Aconitum carmichaelii

Aconitum carmichaelii is a high-value medicinal herb widely used across China,Japan,and other Asian countries.Aconitine-type diterpene alkaloids(DAs)are the characteristic compounds in Aconitum.Although six transcriptomes,based on short-read next generation sequencing technology,have been reported from the Aconitum species,the terpene synthase(TPS)corresponding to DAs biosynthesis remains unidentified.We apply a combination of Pacbio isoform sequencing and RNA sequencing to provide a comprehensive view of the A.carmichaelii transcriptome.Nineteen TPSs and five alternative splicing isoforms belonging to TPS-b,TPS-c,and TPS-e/f subfamilies were identified.In vitro enzyme reaction analysis functional identified two sesqui-TPSs and twelve di TPSs.Seven of the TPS-c subfamily genes reacted with GGPP to produce the intermediate ent-copalyl diphosphate.Five Ac KSLs separately reacted with ent-CPP to produce ent-kaurene,ent-atiserene,and ent-13-epi-sandaracopimaradie:a new diterpene found in Aconitum.Ac TPSs gene expression in conjunction DAs content analysis in different tissues validated that ent-CPP is the sole precursor to all DAs biosynthesis,with Ac KSL1,Ac KSL2 s and Ac KSL3-1 responsible for C20 atisine and napelline type DAs biosynthesis,respectively.These data clarified the molecular basis for the C20-DAs biosynthetic pathway in A.carmichaelii and pave the way for further exploration of C19-DAs biosynthesis in the Aconitum species.

C_(19)-Diterpenoid alkaloid arabinosides from an aqueous extract of the lateral root of Aconitum carmichaelii and their analgesic activities

Eight new C_(19)-diterpenoid alkaloid arabinosides, named aconicarmichosides E–L(1–8), were isolated from an aqueous extract of the lateral roots of Aconitum carmichaelii(Fu Zi). Their structures were determined by spectroscopic and chemical methods including 2D NMR experiments and acid hydrolysis. Compounds 1–8, together with the previously reported four neoline 14-O-arabinosides from the same plant, represent the only examples of glycosidic diterpenoid alkaloids so far. At a dose of 1.0 mg/kg(i.p.), as compared with the black control, compounds 1, 2, and 4–6 exhibited analgesic effects with 465.6% inhibitions against acetic acid-induced writhing of mice. Structure–activity relationship was also discussed.

Two New C19-Diterpenoid Alkaloids with Anti-inflammatory Activity from Aconitum iochanicum

Two new C ig-diterpenoid alkaloids, 7,8-epoxy-franchetine （1） and N（19）-en-austroconitine A （2）, were isolated from Aconitum iochanicum. Compound 1 was a new C19-diterpenoid alkaloid with a 7,8-epoxy unit. Their structures were elucidated by comprehensive spectroscopic analyses including UV, IR, MS, 1D and 2D NMR. Biological ac- tivity tests indicated that two new compounds exhibited inhibitory activity against nitric oxide （NO） production in LPS-activated RAW264.7 macrophages. Compared with positive control, the two new compounds showed weak an- ti-inflammatory effects with the inhibition rate of 27.3% and 29.2%, respectively.

Two New Diterpenoid Alkaloids from Spiraea japonica L. f. var.fortunei （Planchon） Rehd.

Abstract: Two new hetisine-type C20-diterpenoid alkaloids named spiraqine (1) and 6-hydroxylspiraqine (2), and four known alkaloids, namely spiredine (3), spiradine A (4), spiradine B (5), and spirasine V/VI (6), were isolated from Spiraea japonica L. f. var. fortunei(Planchon) Rehd. The structures of the alkaloids were elucidated using nuclear magnetic resonance analysis (1H-NMR, 13C-NMR, DEPT, HMQC, and HMBC) and mass spectrometry data.

New C_(20)-diterpenoid alkaloids from Aconitum sinomontanum

Two new denudatine-type C20-diterpenoid alkaloids, named sinomontanidines A （1） and B （2）, were isolated from the roots ofAconitum sinomontanum Nakai. Their structures were elucidated by extensive analysis of 1D, 2D NMR, and MS data.

A minor arcutine-type C20-diterpenoid alkaloid iminium constituent of“fu zi”

A rare arcutine-type C_（20）-diterpenoid alkaloid, named aconicarmicharcutinium A and obtained as hydroxide（1） and trifluoroacetate（1a）, was characterized as a minor constituent of ＂fu zi＂（the lateral roots of Aconitum carmichaelii）. The structures of 1 and 1a were elucidated by comprehensive analysis of spectroscopic data including^（19）F and 2D NMR experiments. Compounds 1 and 1a represent the first examples of the arcutine-type C_（20）-diterpenoid alkaloid iminium.