Two New 11‐Hydroxy‐Substituted Gelsedine‐Type Indole Alkaloids from the Stems of Gelsemium elegans

Two new 11‐hydroxy‐substituted gelsedine‐type indole alkaloids, named 11,14‐dihydroxygelsenicine ( 1 ) and 11‐hydroxygelsenicine ( 2 ), together with six known alkaloids, i.e., koumine, gelsemine, 14‐hydroxygelsenicine, 11‐hydroxyhumantenine, gelsenicine, and (19Z)‐akuammidine, were isolated from the EtOH extract of the stems of Gelsemium elegans Benth. Their structures were determined mainly by means of spectroscopic analyses including HR‐ESI‐MS and 2D‐NMR (HSQC, HMBC, ¹H,¹H‐COSY). The configuration of 1 was confirmed by X‐ray‐diffraction analysis.     

Two New Lycopodine Alkaloids from Huperzia serrata

Two new lycopodine alkaloids, (12β)‐12‐hydroxyhuperzine G ( 1 ) and (5β,6β,15α)‐15‐methyllycopodane‐5,6‐diol ( 2 ), were isolated from the whole plants of Huperzia serrata, together with six known compounds, huperzines A, B, and G, phlegmariurine B, (8β)‐8‐hydroxyphlegmariurine B, and lycoposerramine D. Their structures were elucidated on the basis of spectroscopic analysis, including HR‐ESI‐MS, ¹H‐ and ¹³C‐NMR, DEPT, ¹H,¹H‐COSY, HSQC, HMBC, and NOESY data.     

Habaenines A and B,Two New Norditerpenoid Alkaloids from Aconitum habaense

Two new norditerpenoid alkaloids, habaenine A and B ( 1 and 2 ), together with two known compounds, were isolated from Aconitum habaense. The structures of the new compounds were elucidated on the basis of spectral analyses as (1α,6α,16β)‐8‐(acetyloxy)‐20‐ethyl‐13‐hydroxy‐1,6,16‐trimethoxy‐4‐(methoxymethyl)‐19‐oxoaconitan‐14‐yl 4‐methoxybenzoate ( 1 ) and (1α,6α,16β)‐8‐(acetyloxy)‐13‐hydroxy‐1,6,16‐trimethoxy‐4‐(methoxymethyl)‐aconitan‐14‐yl 4‐methoxybenzoate ( 2 ).     

Three New Pregnane Alkaloids from Pachysandra terminalis

Three new pregnane alkaloids, pachystermine C ( 1 ), pachysanamine A ( 2 ), and pachysanamine B ( 3 ), together with four known ones, pachystermine B ( 4 ), pachysamine A ( 5 ), (20S)‐20‐(dimethylamino)‐16α‐hydroxy‐3β‐(3′α‐isopropyl)lactam‐5α‐pregnan‐4‐one ( 6 ), and E‐salignone ( 7 ), were isolated from Pachysandra terminalis. The chemical structures of the new alkaloids were elucidated by spectroscopic methods. All the compounds were evaluated for their inhibitory activities against HL‐60, SMMC‐7721, A‐549, MCF‐7, and SW480 cell lines, some of the compounds showed stronger cytotoxicity for the test cell lines, especially compounds 2 , 3 , and 7 .     

Three New Indole Alkaloids from the Leaves of Alstonia scholaris

Three new akuamillan‐type indole alkaloids, i.e., 5‐methoxystrictamine (=methyl (5β,16R,19E)‐5‐methoxyakuammilan‐17‐oate; 1 ), methyl (16R,19E)‐1,2‐dihydro‐16‐(hydroxymethyl)‐5‐oxoakuammilan‐17‐oate ( 2 ), and methyl (2β,16R,19E)‐4,5‐didehydro‐1,2‐dihydro‐2‐hydroxy‐16‐(hydroxymethyl)akuammilan‐4‐ium‐17‐oate chloride ( 3 ), have been isolated from the leaves of Alstonia scholaris, together with ten known compounds. Their structures were determined by spectroscopic means. None of the constituents showed significant cytotoxic activity towards WT cells.     

Three New Indole Alkaloids from the Leaves of Kopsia officinalis

Three new indole alkaloids, 11,12‐de(methylenedioxy)danuphylline ( 1 ), methyl (2β,11β,12β,19α)‐6,7‐didehydro‐8,21‐dioxo‐11,21‐cycloaspidospermidine‐2‐carboxylate ( 2 ), and (2β,5β)‐aspidofractinin‐16‐ol ( 3 ) were isolated from Kopsia officinalis, together with 16 known compounds. Their structures were determined by spectroscopic methods. The isolated known compound (?)‐12‐methoxykopsinaline displayed antimanic effects in Drosophila, with an IC₅₀ value of 12.5 μg/ml.     

New Diterpene Alkaloids from Aconitum sungpanense var. leucanthum

Five new C₁₉ diterpene alkaloids, leucanthumsines A ( 1 ), B ( 2 ), C ( 3 ), D ( 4 ), and E ( 5 ), were isolated from the Chinese medicinal herb Aconitum sungpanense var. leucanthum, together with the known C₁₉ diterpene alkaloids pseudaconine, neoline, 1‐O‐methyldelphisine, crassicaudine, chasmanine, talatisamine, indaconitine, ezochansmanine, and leueantine D. The structures of these new alkaloids were elucidated by HR‐MS and advanced NMR methods, including ¹H‐ and ¹³C‐NMR (DEPT), ¹H,¹H‐COSY, HMQC, and HMBC experiments.     

Optical Resolution and Structure Determination of New Indolizidine Alkaloids from Elaeocarpus sphaericus

Two new indolizidine alkaloids, (±)‐3‐oxoisoelaeocarpine ( 1 ) and (±)‐elaeocarpine N‐oxide ( 2 ), along with three known alkaloids, (±)‐isoelaeocarpine ( 3 ), (±)‐elaeocarpine ( 4 ), and (?)‐isoelaeocarpiline ( 5 ), were isolated from an EtOH extract of the branches and leaves of Elaeocarpus sphaericus. The structures of these compounds were determined by spectroscopic and chemical methods. Furthermore, enantiomers of compounds 1 and 3 were separated on a chiral CD‐Ph column, and their absolute configurations were determined by TD‐DFT (=time‐dependent density‐functional theory) quantum‐chemical calculations of their electronic circular dichroism (ECD) spectra.     

Three New Sesquiterpene Pyridine Alkaloids from Euonymus fortunei

Three new macrocyclic β‐dihydroagarofuran‐type sesquiterpene pyridine alkaloids, fortuneines A ( 1 ), B ( 2 ), and C ( 3 ), together with the four known alkaloids wilfornine E ( 4 ), aquifoliunine E‐I ( 5 ), euoverrine B ( 6 ), and euojaponine I ( 7 ), were isolated from the aerial parts of Euonymus fortunei. Their structures were elucidated by spectroscopic methods, including HR‐ESI‐MS, ¹H‐ and ¹³C‐NMR, DEPT, ¹H,¹H‐COSY, HSQC, HMBC, and ROESY. This is the first isolation of the above sesquiterpene pyridine alkaloids from this plant, except for compound 6 .     

Three New Atisane Diterpenoids from Spiraea japonica

Three new atisane diterpenoids, spiratisanins A – C ( 1  –  3 , resp.), featuring a phenylacryloxyl substituted ent‐atisane skeleton, were isolated from Spiraea japonica together with two known atisine diterpene alkaloids, spiramine A ( 4 ) and spiradine F ( 5 ). The structures of these new compounds were elucidated as (5β,7α,8α,9β,10α,12α,16β)‐16‐hydroxyatisan‐7‐yl (2E)‐3‐phenylprop‐2‐enoate ( 1 ), (5β,7α,8α,9β,10α,12α,16α)‐16‐hydroxyatisan‐7‐yl (2E)‐3‐phenylprop‐2‐enoate ( 2 ), and (5β,8α,9β,10α,12α,16β)‐16‐hydroxyatisan‐20‐yl (2E)‐3‐phenylprop‐2‐enoate ( 3 ) on the basis of spectroscopic analysis.     

Pregnane‐Type Steroidal Alkaloids of Sarcococca saligna: a New Class of Cholinesterase Inhibitors

Phytochemical investigation of Sarcococca saligna by extensive bioassay‐guided fractionation resulted in the isolation of the pregnane‐type steroidal alkaloids 1 – 15 , i.e. of the five new compounds 1 – 5 and the ten known alkaloids 6 – 15 . The structures of the new alkaloids salignenamide C ( 1 ), salignenamide D ( 2 ), 2β‐hydroxyepipachysamine D ( 3 ), salignenamide E ( 4 ), and salignenamide F ( 5 ) were elucidated with the help of modern spectroscopic techniques, while the known alkaloids axillarine C ( 6 ), axillarine F ( 7 ), sarcorine ( 8 ), N³‐demethylsaracodine ( 9 ), saligcinnamide ( 10 ), salignenamide A ( 11 ), vaganine A ( 12 ), axillaridine A ( 13 ), sarsalignone ( 14 ), and sarsalignenone ( 15 ) were identified by comparing their spectral data with those reported earlier. Inhibition of electric‐eel acetylcholinesterase (EC 3.1.1.7) and horse‐serum butyrylcholinesterase (EC 3.1.1.8) by alkaloids 1 – 15 were investigated. These new cholinesterase inhibitors may act as potential leads in the discovery of clinically useful inhibitors for nervous‐system disorders, particularly by reducing memory deficiency in Alzheimer's disease patients by potentiating and effecting the cholinergic transmission process. These compounds were found to inhibit both enzymes in a concentration‐dependent fashion with the IC₅₀ values ranging from 5.21–227.92 μM against acetylcholinesterase and 2.18–38.36 μM against butyrylcholinesterase.     

C19 and C20 Diterpene Alkaloids from Aconitum toxicum Rchb.

Acotoxinine ( 1 ), a new norditerpene alkaloid, was isolated from the roots of Aconitum toxicum Rchb ., together with the structurally related C₁₉ diterpene alkaloids neoline ( 2 ) and aconitine ( 3 ) and C₂₀ diterpene alkaloids songorine ( 4 ) and songoramine ( 5 ). The structures were elucidated by HR‐MS and advanced NMR methods, including ¹H‐NMR, JMOD, ¹H,¹H‐COSY, HSQC, and HMBC experiments. This is the first report of C₂₀ diterpenoid alkaloids in Aconitum toxicum.     

Pyrrolizidine Alkaloids from Onosma leptantha

Three new pyrrolizidine alkaloids, leptanthine ( 2 ), its corresponding N‐oxide 1 , and N‐oxide of 3′‐O‐acetylechihumiline ( 3 ), were isolated from the aerial parts of Onosma leptantha, together with two known alkaloids of the same type, echihumiline ( 5 ) and echihumiline N‐oxide ( 4 ). Their structures and configurations were determined by chemical and spectroscopic methods, especially 1D and 2D NMR analyses, including long‐range ¹H,¹⁵N correlations at natural abundance.     

Structure elucidation and NMR assignments of new spirosolane alkaloids from Solanum campaniforme

From the leaves of Solanum campaniforme, two new spirosolane alkaloids β‐acetoxyl‐(25S)‐22βN‐spirosol‐4‐en‐3‐one (1) and β‐hydroxyl‐(25S)‐22βN‐spirosol‐4‐en‐3‐one (4) were isolated along with two other known alkaloids of the same class (25S)‐22βN‐spirosol‐1,4‐dien‐3‐one (2) and (25S)‐22βN‐spirosol‐4‐en‐3‐one (3), which are reported for the first time as natural products. The structures of all alkaloids were established after an extensive analysis by 1D and 2D NMR spectroscopy (COSY, HSQC, HMBC and NOESY) as well as HRESIMS. Copyright © 2012 John Wiley & Sons, Ltd.     

Annosqualine: a Novel Alkaloid from the Stems of Annona squamosa

Annosqualine (=(10′bR)‐1′,5′,6′,10′b‐tetrahydro‐9′‐hydroxy‐7′,8′‐dimethoxyspiro[cyclohexa‐2,5‐diene‐1,2′‐pyrrolo[2,1‐a]isoquinoline]‐3′,4‐dione; 1 ), a novel alkaloid with an unprecedented skeleton, and a new amide, dihydrosinapoyltyramine (=3‐(4‐hydroxy‐3,5‐dimethoxyphenyl)‐N‐[2‐(4‐hydroxyphenyl)ethyl]propanamide; 2 ), were isolated from the stems of Annona squamosa L., together with six known alkaloids. The structures of all compounds were elucidated spectroscopically by means of optical rotation, ¹H‐, ¹³C‐, and 2D‐NMR, and by EI‐MS, or by comparison with the spectral data of authentic samples. A possible biogenetical pathway towards annosqualine ( 1 ) is proposed.     

Two New Lycopodium Alkaloids from Lycopodium obscurum

Two new Lycopodium alkaloids, (+)‐cermizine D N‐oxide ( 1 ) and (8β)‐8‐(acetyloxy)obscurumine A ( 2 ), along with five known compounds, were isolated from the crude alkaloid portion of Lycopodium obscurum. Their structures were elucidated on the basis of spectroscopic data and chemical correlation. All of these alkaloids were tested in an assay for acetylcholine esterase (AChE) inhibitory activity.     

Vinmajorines C – E,Monoterpenoid Indole Alkaloids from Vinca major

Three new monoterpenoid indole alkaloids, vinmajorines C–E ( 1 – 3 ), along with 18 known analogues ( 4 – 21 ), were isolated from the whole plants of Vinca major. The new structures were elucidated as (5α,15β,16R,17α,19β,20α,21β)‐10,17‐dimethoxy‐21‐methyl‐18‐oxa‐5,16‐cycloyohimban‐19‐ol ( 1 ), (5α,15β,16R,17α,20α,21β)‐10‐methoxy‐21‐methyl‐18‐oxa‐5,16‐cycloyohimban‐17‐ol ( 2 ), and (5α,15β,16R,17α,20α,21β)‐10‐methoxy‐21‐methyl‐18‐oxa‐5,16‐cycloyohimban‐17‐yl acetate ( 3 ), respectively, by extensive NMR and MS analysis and comparison with known compounds. Compounds 1 – 3 were evaluated for their cytotoxic activities against five human cancer cell lines, compounds 1 and 3 showing moderate cytotoxic activities.     

Withanolides from Aureliana fasciculata var. fasciculata

In the first phytochemical study of the Aureliana genus (Solanaceae), two new withanolides, 1 and 2 , together with two known sterols, were isolated from the MeOH extract of the leaves of Aureliana fasciculata var. fasciculata. The structures were established as (4S,22R)‐16α‐acetoxy‐5β,6β‐epoxy‐4β,17α‐dihydroxy‐1‐oxowitha‐2,24‐dienolide (aurelianolide A) and (4S,22R)‐16α‐acetoxy‐4β,17α‐dihydroxy‐1‐oxowitha‐2,5,24‐trienolide (aurelianolide B). The new compounds possessed the unusual 16α,17α‐dioxygenated group and were fully characterized by spectroscopic techniques, including ¹H‐ and ¹³C‐NMR (DEPT), as well as 2D‐NMR (HMBC, HMQC, ¹H,¹H‐COSY, NOESY) experiments, and HR‐MS.     

Henrycinols A and B,Two Novel Indole Alkaloids Isolated from Melodinus henryi Craib

Henrycinols A ( 1 ) and B ( 2 ), two novel indole alkaloids, together with three known compounds, (+)‐Δ¹⁴‐vincamine ( 3 ), (+)‐16‐epi‐Δ¹⁴‐vincamine ( 4 ), and (+)‐isoeburnamine ( 5 ), were isolated from the roots of Melodinus henryi Craib . Their structures were established on the basis of 1D‐ and 2D‐NMR spectroscopic analysis. The relative configuration of henrycinols A and B was determined by NOESY analysis.     

Molecular Insight into the Mg2+‐Dependent Allosteric Control of Indole Prenylation by Aromatic Prenyltransferase AmbP1

AmbP1 is a cyanobacterial aromatic prenyltransferase and a dedicated synthase for (R)‐3‐geranyl‐3‐isocyanovinyl indolenine ( 2 ), the biogenetic precursor for hapalindole‐type alkaloids. The regioselective geranylation of cis‐indolyl vinyl isonitrile ( 1 ) by the standalone AmbP1 to give 2 has been shown to require a magnesium ion (Mg²⁺) to suppress the formation of cis‐2‐geranylindolyl vinyl isonitrile ( 3 ). Here, we report high‐resolution crystal structures of AmbP1 in complex with 1 and geranyl S‐thiodiphosphate (GSPP) in the presence and absence of a Mg²⁺ effector. The comparative study of these structures revealed a unique allosteric binding site for Mg²⁺ that modulates the conformation of 1 in the active site of AmbP1 for its selective geranylation. This work defines the structural basis for AmbP1 catalysis in the biogenesis of hapalindole‐type alkaloids and provides the first atomic‐level insight to the allosteric regulation of prenyltransferases.