Three New Alkaloids from the Leaves of Uncaria rhynchophylla

Three new alkaloids, 2′‐O‐β‐D ‐glucopyranosyl‐11‐hydroxyvincoside lactam ( 1 ), 22‐O‐demethyl‐22‐O‐β‐D ‐glucopyranosylisocorynoxeine ( 2 ), and (4S)‐corynoxeine N‐oxide ( 3 ) were isolated from the leaves of Uncaria rhynchophylla, together with four known tetracyclic oxindole or indole alkaloids, isocorynoxeine N‐oxide ( 4 ), rhynchophylline N‐oxide ( 5 ), isorhynchophylline N‐oxide ( 6 ), and dihydrocorynantheine ( 7 ), and an indole alkaloid glycoside, strictosidine ( 8 ). The structures of 1 – 3 were elucidated by spectroscopic methods including UV, IR, ESI‐TOF‐MS, 1D‐ and 2D‐NMR, as well as CD experiments. The activity assay showed that 8 (IC₅₀=8.3 μM ) exhibited potent inhibitory activity on lipopolysaccharide(LPS)‐induced nitrogen monoxide (NO) release in N9 microglia cells. However, only weak inhibitory activities were observed for 1 – 7 (IC₅₀>100 μM for 1 – 6 or >30 μM for 7 ).     

Lycodine‐Type Alkaloids from Lycopodium casuarinoides

Two new lycodine‐type alkaloids, huperzinine N‐oxide ( 1 ) and 8,15‐dihydrohuperzinine ( 2 ) as well as five known compounds, huperzinine ( 3 ), huperzine B ( 4 ), huperzine D ( 5 ), N‐demethylhuperzinine ( 6 ), and β‐obscurine ( 7 ), were isolated from the club moss Lycopodium casuarinoides. The structures of 1 and 2 were elucidated by spectroscopic methods and chemical transformation. The absolute configuration of 1 was established by chemical correlation with 3 , and that of 2 was determined by its CD spectrum.     

Lycopodine‐Type Lycopodium Alkaloids from Huperzia serrata

Eleven Lycopodium alkaloids with a lycopodine‐type skeleton were isolated from the basic material of the whole plant of Huperzia serrata (Thunb .) Trev. (Huperziaceae). Among them, 12‐epilycodoline N‐oxide (=(12α,15R)‐12‐hydroxy‐15‐methyllycopodan‐5‐one N‐oxide; 1 ), 7‐hydroxylycopodine (=(15S)‐7‐hydroxy‐15‐methyllycopodan‐5‐one; 2 ), and 4,6α‐dihydroxylycopodine (=(6α,15R)‐4,6‐dihydroxy‐15‐methyllycopodan‐5‐one; 3 ) are new compounds. Their structures were identified spectroscopically, especially by means of 1D‐ and 2D‐NMR.     

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.     

Two New Lycodine Alkaloids from Lycopodiastrum casuarinoides

Two new lycodine alkaloids, 11β‐methoxyhuperzine B ( 1 ) and 16‐oxohuperzinine ( 2 ), together with seven known ones, huperzinine N‐oxide, huperzine D, casuarinine A, huperzine B, casuarinine B, huperzinine, and N‐methyllycodine, were isolated from whole plants of Lycopodiastrum casuarinoides. Their structures were elucidated by spectroscopic methods, including NMR and MS experiments.     

Monoterpenoid Indole Alkaloids Bearing an N4‐Iridoid from Gelsemium elegans

Five new alkaloids, gelseganines A–D ( 1 – 4 ) and humantenine N₄‐oxide ( 5 ), were isolated from the stems and leaves of Gelsemium elegans. Compounds 1 – 4 represent a rare class of monoterpenoid indole alkaloids that bear an N₄‐iridoid unit. The structures of 1 – 5 were determined by spectroscopic analysis, single‐crystal X‐ray diffraction, and chemical correlation, and their absolute configurations were elucidated by CD analysis. A plausible biogenetic pathway for alkaloids 1 – 5 was also postulated.     

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.     

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.     

Two New Bis‐alkaloids from the Aerial Part of Piper flaviflorum

Two new bis‐alkaloids, flavifloramides A ( 1 ) and B ( 2 ), as well as two known alkaloids, N‐trans‐feruloyltyramine ( 3 ) and paprazine ( 4 ), were isolated from the aerial part of Piper flaviflorum. The structures of the new compounds were elucidated by spectroscopic analyses, including 2D‐NMR techniques.     

A New Lycopodine Alkaloid from Phlegmariurus yunnanensis Ching

A new lycopodine alkaloid, 15α‐methyllycopodane‐5β,6β‐diol N‐oxide ( 1 ), was isolated from the whole plants of Phlegmariurus yunnanensis Ching , together with the two known alkaloids 15α‐methyllycopodane‐5β,6β‐diol ( 2 ) and lycoposerramine H ( 3 ), and four serratene‐type triterpenoids, serratenediol‐3‐acetate ( 4 ), serratenediol ( 5 ), lycocryptol ( 6 ), and serratriol ( 7 ). Their structures were elucidated on the basis of spectroscopic analyses, including HR‐ESI‐MS, ¹H‐ and ¹³C‐NMR, DEPT, ¹H,¹H‐COSY, HSQC, HMBC, and NOESY.     

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.     

Amaryllidaceae Alkaloids from Lycoris radiata

A phytochemical investigation on bulbs of Lycoris radiata resulted in the isolation of three new Amaryllidaceae alkaloids, named 5,6‐dehydrodihydrolycorine ( 1 ), 6β‐acetoxycrinamine ( 2 ), and (+)‐8‐O‐acetylhomolycorine α‐N‐oxide ( 3 ), together with eleven known alkaloids, 4 – 14 . The structures of the new alkaloids were established by means of spectroscopic methods, and the known compounds were identified by comparison of their data with those in the literature. Compound 2 showed cytotoxicity against HL‐60, A‐549, and MCF‐7 cells, with IC₅₀ values of 8.1, 24.3, and 15.0 μM , respectively.     

GC‐MS of amaryllidaceous galanthamine‐type alkaloids

Galanthamine‐type alkaloids produced by plants of the Amaryllidaceae family are potent acetylcholinesterase inhibitors. One of them, galanthamine, has been marketed as a hydrobromide salt for the treatment of Alzheimer's disease. In the present work, gas chromatography with electron impact mass spectrometry (GC‐EIMS) fragmentation of 12 reference compounds isolated from various amaryllidaceous plants and identified by spectroscopic methods (1D and 2D nuclear magnetic resonance, circular dichroism, high‐resolution MS (HRMS) and EIMS) was studied by tandem mass spectrometry (GC‐MS/MS) and accurate mass measurements (GC‐HRMS). The studied compounds showed good peak shape and efficient GC separation with a GC‐MS fragmentation pattern similar to that obtained by direct insertion probe. With the exception of galanthamine‐N‐oxide and N‐formylnorgalanthamine, the galanthamine‐type compounds showed abundant [M]^+. and [M‐H]⁺ ions. A typical fragmentation pattern was also observed, depending on the substituents of the skeleton. Based on the fragmentation pathways of reference compounds, three other galanthamine‐type alkaloids, including 3‐O‐(2′‐butenoyl)sanguinine, which possesses a previously unelucidated structure, were identified in Leucojum aestivum ssp. pulchelum, a species endemic to the Balearic islands. GC‐MS can be successfully applied to Amaryllidaceae plant samples in the routine screening for potentially new or known bioactive molecules, chemotaxonomy, biodiversity and identification of impurities in pharmaceutical substances. Copyright © 2012 John Wiley & Sons, Ltd.     

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.     

New Indole Alkaloids from Rauvolfia yunnanensis

Three new indole alkaloids, 10‐methoxy‐16‐de(methoxycarbonyl)pagicerine ( 1 ), (5β)‐17‐O‐deacetyl‐5,11‐dimethoxyakuammiline ( 2 ), and ((16S,19E)‐N¹‐(hydroxymethyl)isositsirikine ( 3 ) were isolated from the roots of Rauvolfia yunnanensis, together with seven known alkaloids. The structures of the new compounds were elucidated by in‐depth spectroscopic and mass‐spectrometric analyses.     

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.     

Rapid structural determination of alkaloids in a crude extract of Stemona saxorum by high‐performance liquid chromatography/electrospray ionization coupled with tandem mass spectrometry

The electrospray ionization (ESI) mass spectrometric behavior of five Stemona alkaloids, stemokerrin, oxystemokerrin, oxystemokerrilactone, oxystemokerrin N‐oxide and stemokerrin N‐oxide, was studied using an ESI tandem mass technique (MSⁿ). These compounds, isolated from Stemona saxorum endemic in Vietnam, represent a class of alkaloids containing a pyrido[1,2‐a]azepine A,B‐ring core with a 1‐hydroxypropyl side chain attached to C‐4. Their fragmentation pathways were elucidated by ESI‐MSⁿ results and the elemental composition of the major product ions was confirmed by accurate mass measurement. In order to rationalize some fragmentation pathways, the relative Gibbs free energies of some product ions were estimated using the B3LYP/6‐31+G(d) method. Based on the ESI‐MSⁿ results of five reference compounds, a reversed‐phase high‐performance liquid chromatography with tandem mass spectrometry (RP‐HPLC/MSⁿ) method was developed for the characterization of Stemona alkaloids with a pyrido[1,2‐a]azepine A,B‐ring core from the extract of S. saxorum. A total of 41 components were rapidly identified or tentatively characterized, of which 12 compounds were identified as Stemona alkaloids with a pyrido[1,2‐a]azepine A,B‐ring core, including four new compounds. This method is convenient and sensitive, especially for minor components in complex natural product extracts. Copyright © 2009 John Wiley & Sons, Ltd.     

New Pyrrole Alkaloids with Bulky N‐Alkyl Side Chains Containing Stereogenic Centers from Lycium chinense

Four new pyrrole alkaloids, methyl 2‐[2‐formyl‐5‐(methoxymethyl)‐1H‐pyrrol‐1‐yl]propanoate ( 1 ), methyl 2‐[2‐formyl‐5‐(methoxymethyl)‐1H‐pyrrol‐1‐yl]‐3‐(4‐hydroxyphenyl)propanoate ( 2 ), dimethyl 2‐[2‐formyl‐5‐(methoxymethyl)‐1H‐pyrrol‐1‐yl]butanedioate ( 3 ), and dimethyl 2‐[2‐formyl‐5‐(methoxymethyl)‐1H‐pyrrol‐1‐yl]pentanedioate ( 4 ), were isolated from the AcOEt extract of the fruits of Lycium chinense Miller (Solanaceae). The stereogenic center C(2) in the bulky N‐alkyl side chain in each of 1 – 4 seems to hold the H‐atoms of nearby CH₂ groups, CH₂(7′) and CH₂(3) (if R≠H), leading to two different chemical shifts in the ¹H‐NMR spectrum due to their diastereotopic characteristics. In the ¹H‐NMR data of each of 2 – 4 , the enhancement of H? C(2) signal was inhibited by the R group, probably due to steric hindrance, and its chemical shift was influenced by the anisotropy effect. The structures of 1 – 4 were elucidated by analysis of various spectroscopic data, including 1D‐ and 2D‐NMR.     

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.     

Concise Syntheses of bis‐Strychnos Alkaloids (−)‐Sungucine, (−)‐Isosungucine,and (−)‐Strychnogucine B from (−)‐Strychnine

The first chemical syntheses of complex, bis‐Strychnos alkaloids (?)‐sungucine ( 1 ), (?)‐isosungucine ( 2 ), and (?)‐strychnogucine B ( 3 ) from (?)‐strychnine ( 4 ) is reported. Key steps included (1) the Polonovski–Potier activation of strychnine N‐oxide; (2) a biomimetic Mannich coupling to forge the signature C23?C5′ bond that joins two monoterpene indole monomers; and (3) a sequential HBr/NaBH₃CN‐mediated reduction to fashion the ethylidene moieties in 1 – 3 . DFT calculations were employed to rationalize the regiochemical course of reactions involving strychnine congeners.