Gastrodin Derivatives from Gastrodia elata

Nine new gastrodin derivatives,including seven p-hydroxybenzyl-modified gastrodin ethers(1-7),6′-O-acetylgastrodin(8),and 4-[α-d-glucopyranosyl-(1→6)-β-d-glucopyranosyloxy]benzyl alcohol(9),together with seven known derivatives,were isolated from an aqueous extract of Gastrodia elata(“tian ma”)rhizomes.Their structures were determined by spectroscopic and chemical methods as well as single crystal X-ray diffraction.Compounds 1-4,7,10,and 11 were also isolated from a reaction mixture by refluxing gastrodin and p-hydroxybenzyl alcohol in H2O.As both gastrodin and p-hydroxybenzyl alcohol exist in the plant,the reaction results provide evidence for the production and increase/decrease of potential effective/toxic components when“tian ma”is decocted solely or together with ingredients in Chinese traditional medicine formulations,though the isolates were inactive in the preliminarily cell-based assays at concentrations of 10μM.Moreover,using ultra-performance liquid chromatography high-resolution electrospray ionization mass spectrometry(UPLC-HRESIMS),4,7,10,and 11,as well as component variations,were detectable in the freshly prepared extracts of different types of samples,including the freeze-dried fresh G.elata rhizomes.

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.

Codonopiloneolignanin A, a polycyclic neolignan with a new carbon skeleton from the roots of Codonopsis pilosula

A neolignan codonopiloneolignanin A（1） with a novel 2,9：20,9：7,70-tricyclo-8,90-neolignane skeleton was isolated from an aqueous extract of the Codonopsis pilosula roots. Its structure including the absolute configuration was elucidated by extensive spectroscopic analysis, including 2D NMR and electronic circular dichroism calculation. The proposed biosynthetic pathway of compound 1 is also discussed.

Two pairs of unusual scalemic enantiomers from Isatis indigotica leaves

Two pairs of unusual scalemic enantiomers with a dimethoxyphenyl）ethyl]-2-methoxyindolin-3-one, novel carbon skeleton of 2-[1′-（4＂-hydroxy-3＂,5＂- named isatidifoliumindolinones A-D （1-4）, were isolated from an aqueous extract of lsatis indigotica leaves （da qing ye）. Their structures including absolute configurations were determined by spectroscopic data analysis combined with comparison of their experimental CD and calculated ECD spectra. Validity of the ECD spectra calculation to assign the absolute configurations is discussed. Plausible biosynthetic pathways of 1-4 are proposed. Stereochemistry-dependent activity against LPS-induced NO production in BY2 cells was observed, and among the stereoisomers compound 4 is most active.

Secoeuphoractin,a minor diterpenoid with a new skeleton from Euphorbia micractina

A minor diterpenoid with a novel carbon skeleton,secoeuphoractin（1）,was isolated from an ethanol extract of the roots of Euphorbia micractina.Its structure including the absolute configuration was determined by extensive spectroscopic studies,especially by 2D NMR and CD data analysis,in combination with a plausible biosynthetic pathway associated with co-occurring diverse diterpenoids.This compound showed activity against HIV-1 replication with an IC_（50） value of 1.76 ± 0.61 μmol/L.

Antiviral enantiomers of a bisindole alkaloid with a new carbon skeleton from the roots of Isatis indigotica

A pair of indole alkaloid enantiomers with a novel bisindolylacetamide skeleton, insatindibisindolamides A and B（1a and 1b）, was isolated from an aqueous extract of Isatis indigotica roots. The enantiomers were separated by chiral HPLC. Their structures and absolute configurations were elucidated by extensive spectroscopic analysis, including 2D NMR, X-ray crystallography, and electronic CD（ECD） calculation. The proposed biosynthetic pathway and preliminary investigations of the biological activity of compounds 1a and 1b are also discussed.

Two 2-(quinonylcarboxamino)benzoates from the lateral roots of Aconitum carmichaelii

Two new 2-（quinonylcarboxamino）benzoates, named aconicarmiquinamides A （1） and B （2）, were isolated from an aqueous extract of the lateral roots of Aconitum carmichaelii. Their structures were determined by spectroscopic data analysis, and confirmed by comparison with synthetic methyl 3.6- bis（ diethylamino ）benzoqunonylcarboxylate （3）.

Two homosecoiridoids from the flower buds of Lonicera japonica

Two new homosecoiridoids, named loniaceticiridoside （1） and lonimalondialiridoside （2）, were isolated from an aqueous extract of the flower buds of Lonicera japonica. Their structures including the absolute configuration were determined by extensive spectroscopic studies, especially by 2D NMR and CD data analysis. A proposed biosynthetic pathway and preliminary investigations of the biological activity of compounds 1 and 2 are also discussed.

Unprecedented C_(19)-diterpenoid alkaloid glycosides from an aqueous extract of“fu zi”:Neoline 14-O-L-arabinosides with four isomeric L-anabinosyls

Four structurally unprecedented aconitane-type C_（19）-diterpenoid alkaloid glycosides with isomeric arabinosyls, named aconicarmichosides A–D（1–4）, were isolated from an aqueous extract of ＂fu zi＂, the lateral roots of Aconitum carmichaelii. Their structures were determined as neoline 14-O-a-and 14-O-b-L-arabinopyranosides（1 and 2） and 14-O-a-and 14-O-b-L-arabinofuranosides（3 and 4）, by spectroscopic and chemical methods including 2D NMR experiments and acid hydrolysis. Compounds 1–4 represent the first examples of glycosidic diterpenoid alkaloids.

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.

Isatindigodiphindoside,an alkaloid glycoside with a new diphenylpropylindole skeleton from the root of Isatis indigotica

A novel indole alkaloid glycoside with an unprecedented 2-（diphenylpropyl）indole skeleton, isatindigodiphindoside （1）, was isolated from an aqueous extract of the roots of lsatis indigotica. The structure was determined by extensive spectroscopic studies, especially by 2D NMR data analysis combined with enzymatic hydrolysis and ECD calculations. Plausible biosynthetic pathways of compound 1 are also discussed.

Gastrolatathioneine,an unusual ergothioneine derivative from an aqueous extract of "tian ma":A natural product co-produced by plant and symbiotic fungus

Gastrolatathioneine （1）, an unusual natural product derived from ergothioneine, a fungal amino acid containing an imidazole-2-thione moiety, was isolated from an aqueous extract of ＂tian ma＂ （the Gastrodia elata rhizomes）. The structure of 1 including the absolute configuration was determined by extensive spectroscopic data analysis, combined with comparison of an experimental circular dichroism spectrum and calculated electronic circular dichroism spectra of stereoisomers, and confirmed by X-ray crystallography. The natural origin of 1 was proved by HPLC-ESIMS analysis of the crude extract. A biogenetic pathway of I is proposed on the basis of metabolic post-modification of ergothioneine that is biosynthesized by a symbiotic fungus. The plant and symbiotic fungus are co-uroducers of 1.

Gastradefurphenol,a minor 9,9＇-neolignan with a new carbon skeleton substituted by two p-hydroxybenzyls from an aqueous extract of “tian ma”

Gastradefurphenol（1）,a minor 9.9＇-neolignan with a novel carbon skeleton substituted by two phydroxybenzyls was isolated from an aqueous extract of the Gastrodia elata rhizomes（tian ma）.Its structure was determined by extensive spectroscopic data analysis.Solvent-dependent free rotational restriction of bonds and equilibrium of two molecular states are discussed by comparison of the NMR spectroscopic data of 1 in acetone-d6 with those in CD3OD.A biogenetic pathway of 1 is postulated to be associated with metabolic processes of L-tyrosine.