Alkaloids of Zanthoxylum monophyllum and Z. punctatum

The known alkaloids N-methylcorydine and magnoflorine were major constituents of stems and branches of Zanthoxylum punctatum (Rutaceae). Berberine was the major alkaloid of Z. monophyllum, which also contained a new pyrano-2-quinolone alkaloid, zanthophylline, and its desmethyl analog. Zanthophylline has an —NCH₂OAc functional group which is readily hydrolyzed by dilute acid. Methyl vanillate and the furocoumarin columbianetin were also found in Z. monophyllum.     

The C19-diterpenoid alkaloids of Delphinium bicolor

Eight C₁₉-diterpenoid alkaloids were isolated from Delphinium bicolor, including the neurotoxic methyllycaconitine and a new alkaloid, bicolorine 6-O-acetate.     

Liriodendronine,an oxoaporphine pigment from discolored sapwood of Liriodendron tulipifera

A new violet oxoaporphine alkaloid. liriodendronine, has been isolated from the discolored sapwood of Liniodendron tulipifera and its structure determined by spectroscopic methods and by conversion into a corunnine-type compound, 2-O,N-dimethylliriodendronine. UV studies demonstrated that the compound exists primarily as a quinone-methide in a neutral medium, a dianion in base, an isoquinolinium ion in weak acid, and as an antiaromatic conjugate acid in conc H₂SO₄.     

Two non-hydroxylated alkaloids in Crinum augustum

Several alkaloids were isolated from Crinum augustum grown in Assiut, Egypt. Two were identified as lycorine and buphanisine. In addition two new non-hydroxylated alkaloids of identical molecular formula C₁₇H₁₉NO₄ were investigated by spectroscopic methods. The gross structure of the first, termed augustine, belongs to the 1,2-epoxy-5, 10-b-ethanophenanthridine-type. In contrast the second could not be related to any of the known alkaloid types of the Amaryllidaceae.     

From anti-fouling to biofilm inhibition: New cytotoxic secondary metabolites from two Indonesian Agelas sponges

Chemical investigation of Indonesian marine sponges Agelas linnaei and A. nakamurai afforded 24 alkaloid derivatives representing either bromopyrrole or diterpene alkaloids. A. linnaei yielded 16 bromopyrrole alkaloids including 11 new natural products with the latter exhibiting unusual functionalities. The new compounds include the first iodinated tyramine-unit bearing pyrrole alkaloids, agelanesins A–D. These compounds exhibited cytotoxic activity against L5178Y mouse lymphoma cells with IC₅₀ values between 9.25 and 16.76 μM. Further new compounds include taurine acid substituted bromopyrrole alkaloids and a new dibromophakellin derivative. A. nakamurai yielded eight alkaloids among them are three new natural products. The latter include the diterpene alkaloids (?)-agelasine D and its oxime derivative and the new bromopyrrole alkaloid longamide C. (?)-Agelasine D and its oxime derivative exhibited cytotoxicity against L5178Y mouse lymphoma cells (IC₅₀ 4.03 and 12.5 μM, respectively). Furthermore, both agelasine derivatives inhibited settling of larvae of Balanus improvisus in an anti-fouling bioassay and proved to be toxic to the larvae. (?)-Agelasine D inhibited the growth of planktonic forms of biofilm forming bacteria S. epidermidis (MIC < 0.0877 μM) but did not inhibit biofilm formation whereas the oxime derivative showed the opposite activity profile and inhibited only biofilm formation but not bacterial growth. The structures of the isolated secondary metabolites were elucidated based on extensive spectroscopic analysis involving one- and two-dimensional NMR as well as mass spectrometry and comparison with literature data.     

Dolabellane-type diterpene alkaloids from Nigella glandulifera

A new dolabellane-type diterpene alkaloid, deoxynigellamine, together with three known dolabellane-type diterpene alkaloids, were isolated from the seeds of Nigella glandulifera. Their structures were identified as nigellamine A₁ (1), nigellamine A₂ (2), nigellamine B₁ (3) and nigeglamine (4), respectively, based on spectroscopic analysis and by comparison of their spectral data with those reported previously in the literature.     

(−)-3β-13α-dihydroxylupanine from cytisus scoparius

A new lupin alkaloid, (−)-3β,13α-dihydroxylupanine was isolated from Cytisus scoparius together with five known sparteine-type lupin alkaloids and tyramine. The absolute structure of the new alkaloid was confirmed by comparison of the natural product with the synthetic sample derived from (+)-13-hydroxylupanine. It was also shown that the alkaloid constituents of C. scoparius differed considerably in the aerial parts, flowers and seeds.     

Neopetrosiamine A,biologically active bis-piperidine alkaloid from the Caribbean sea sponge Neopetrosia proxima

A new tetracyclic bis-piperidine alkaloid, neopetrosiamine A (1), has been extracted from the marine sponge Neopetrosia proxima collected off the west coast of Puerto Rico. The structure of compound 1 was elucidated by analysis of spectroscopic data coupled with careful comparisons of its ¹H and ¹³C NMR data with those of a well-known 3-alkylbis-piperidine alkaloid model. The new alkaloid displayed strong in vitro cytotoxic activity against a panel of cancer cell lines as well as in vitro inhibitory activity against the pathogenic microbes Mycobacterium tuberculosis and Plasmodium falciparum.     

Five new diterpenoid alkaloids from Aconitum sczukinii Turcz.

Ten diterpenoid alkaloids, including five new ones, sczukiniline A–E (1-5), were isolated from the root of Aconitum sczukinii. Their structures were elucidated based on the interpretation of spectroscopic data (HRESI-MS, IR, 1D- and 2D-NMR). Among the five new diterpenoid alkaloids, 1-3 are hetidine-type C₂₀-diterpenoid alkaloids, while compounds 4 and 5 are lycoctonine-type C₁₉-diterpenoid alkaloids. Noteworthily, sczukiniline A (1) features a novel ester group between C-12 and C-14, forming a D ring containing a lactone structure, resulting in a new skeleton of hetidine-type C₂₀-diterpenoid alkaloid.     

Nb-demethylalstophylline oxindole an oxindole alkaloid from the leaves of Alstonia macrophylla

An oxindole alkaloid, N_b-demethylalstophylline oxindole has been isolated from the leaves of Alstonia macrophylla. Its structure has been elucidated on the basis of spectroscopic studies.     

Pachyovatamine,a bisbenzylisoquinoline alkaloid,and other alkaloids from Pachygone ovata

A new dibenzo-p-dioxin biphenyl bisbenzylisoquinoline alkaloid, pachyovatamine, has been isolated from an extract of the leaves and stems of Pachygone ovata from Sri Lanka. The alkaloid was characterized by a consideration of its physicochemical data and conversion to O-acetyltiliacorinine. Pachygonamine, N-methylpachygonamine and tiliamosine were also isolated from the same extract.     

An aporphinoid alkaloid from Pseuduvaria macrophylla

Chromatographic separation of the alkaloid fraction of the methanol extract from the stem bark of Pseuduvaria macrophylla resulted in the isolation of a new aporphinoid alkaloid, 1,2,3-trimethoxy-4,5-dioxo-6a,7-dehydroaporphine, together with possibly the known O-methylmoschatoline.     

Enzymes from Fungal and Plant Origin Required for Chemical Diversification of Insecticidal Loline Alkaloids in Grass-Epichlo? Symbiota

The lolines are a class of bioprotective alkaloids that are produced by Epichloë species, fungal endophytes of grasses. These alkaloids are saturated 1-aminopyrrolizidines with a C2 to C7 ether bridge, and are structurally differentiated by the various modifications of the 1-amino group: -NH₂ (norloline), -NHCH₃ (loline), -N(CH₃)₂ (N-methylloline), -N(CH₃)Ac (N-acetylloline), -NHAc (N-acetylnorloline), and -N(CH₃)CHO (N-formylloline). Other than the LolP cytochrome P450, which is required for conversion of N-methylloline to N-formylloline, the enzymatic steps for loline diversification have not yet been established. Through isotopic labeling, we determined that N-acetylnorloline is the first fully cyclized loline alkaloid, implying that deacetylation, methylation, and acetylation steps are all involved in loline alkaloid diversification. Two genes of the loline alkaloid biosynthesis (LOL) gene cluster, lolN and lolM, were predicted to encode an N-acetamidase (deacetylase) and a methyltransferase, respectively. A knockout strain lacking both lolN and lolM stopped the biosynthesis at N-acetylnorloline, and complementation with the two wild-type genes restored production of N-formylloline and N-acetylloline. These results indicated that lolN and lolM are required in the steps from N-acetylnorloline to other lolines. The function of LolM as an N-methyltransferase was confirmed by its heterologous expression in yeast resulting in conversion of norloline to loline, and of loline to N-methylloline. One of the more abundant lolines, N-acetylloline, was observed in some but not all plants with symbiotic Epichloë siegelii, and when provided with exogenous loline, asymbiotic meadow fescue (Lolium pratense) plants produced N-acetylloline, suggesting that a plant acetyltransferase catalyzes N-acetylloline formation. We conclude that although most loline alkaloid biosynthesis reactions are catalyzed by fungal enzymes, both fungal and plant enzymes are responsible for the chemical diversification steps in symbio.     

A new dimeric carbazole alkaloid from Murraya koenigii (L.) leaves with α-amylase and α-glucosidase inhibitory activities

A new dimeric carbazole alkaloid, 3,3′,5,5′,8-pentamethyl-3,3′-bis(4-methylpent-3-en-1-yl)-3,3′,11,11′-tetrahydro-10,10′-bipyrano[3,2-a]carbazole, was isolated from the hexane extract of leaves of Murraya koenigii (L.) Sprengel. (Family: Rutaceae). The structure was elucidated based on ¹³C and ¹H NMR, High-Resolution Mass Spectrometry (HRMS), and 2D NMR data. The in vitro antidiabetic activity of the new dimer was investigated in terms of α-amylase and α-glucosidase enzyme inhibition assays. The dimer exhibited significant α-amylase inhibitory activity (IC₅₀ = 30.32 ± 0.34 ppm) and α-glucosidase inhibitory activity (IC₅₀ = 30.91 ± 0.36 ppm).     

Lupin alkaloids from sophora chrysophylla

A new lupin alkaloid, (?)-mamanine N-oxide, was isolated from Sophora chrysophylla together with 18 known alkaloids including some unusual lupin alkaloids such as kuraramine, lamprolobine, epilamprolobine, epilamprolobine N-oxide, (+)-mamanine and (?)-pohakuline. It was also shown that the alkaloid constituents of S. chrysophylla differed considerably in the leaves, stems and seeds.     

Accumulation of Ergopeptide Alkaloids in Symbiotic Tall Fescue Grown under Deficits of Soil Water and Nitrogen Fertilizer

The fungus Acremonium coenophialum is endophytically associated with tall fescue (Festuca arundinacea Schreber). Within this symbiotum the fungus produces ergopeptide alkaloids, which are associated with livestock toxicoses. Environmental effects on the production of ergot alkaloids within the symbiotum are unknown. We conducted a greenhouse study of the effects of flooding, nitrogen rate during fertilization (11, 73, and 220 mg of N per pot weekly), nitrogen form (3.4 and 34 mg of N as NH₄⁺ or NO₃^- per pot), and drought stress (-0.03, -0.05, and -0.50 MPa) on ergopeptide alkaloid concentrations in one genotype of nonsymbiotic and symbiotic tall fescue grown in plastic pots. It was determined that the concentration of ergovaline, the major type of ergopeptide alkaloid, was increased but was not as high as that in nonflooded controls. Total ergopeptide and ergovaline concentrations in plants receiving high (220 mg of N per pot) and low (11 mg of N per pot) levels of NH₄NO₃ fertilization were not affected by flooding. The form of nitrogen was important since all concentrations of NO₃^--N increased ergopeptide alkaloid content, as opposed to the effects of NH₄⁺-N, which was effective only at high concentrations (34 mg of N per pot). Ergopeptide concentrations were highest in drought-stressed plants grown at -0.50 MPa and fertilized at the moderate or high N rate. The results suggest that within this genotype, ergopeptide alkaloid biosynthesis by the fungus is not appreciably affected by flooding but is greatly increased by high rates of N fertilization and moderate water deficit.     

Lycopodium Alkaloids from Huperzia serrata and Their Anti-acetylcholinesterase Activities

One new fawcettimine-type alkaloid ( 1 ), one new miscellaneous-type alkaloid ( 2 ), four new lycodine-type alkaloids ( 3 – 6 ), and eight known ones ( 7 – 14 ) were isolated from the whole plants of Huperzia serrata. Their structures and absolute configurations were elucidated based on spectroscopic data, X-ray diffraction, ECD calculation and Mosher's method. Compound 1 was a rare C₁₈N₂-type Lycopodium alkaloid, possessing serratinine skeleton with an amide side chain in C-5. The absolute configuration of the 18-OH of compounds 4 – 6 were first determined by Mosher's method. Moreover, compounds 1 – 14 were assayed anti-acetylcholinesterase effect in vitro, and compound 7 showed significant anti-acetylcholinesterase activity with an IC₅₀ value of 16.18±1.64 μM.     

Spegazzinine,a new inhibitor of mitochondrial oxidative phosphorylation

The effects of spegazzinine, a dihydroindole alkaloid, on mitochondrial oxidative phosphorylation were studied.Spegazzinine inhibited coupled respiration and phosphorylation in rat liver mitochondria. The I₅₀ was 120 μM. Uncouplers released the inhibition of coupled respiration. Arsenate-stimulated mitochondrial respiration was partially inhibited by spegazzinine. The stimulation of mitochondrial respiration by Ca²⁺ and the proton ejection associated with the ATP-dependent Ca²⁺ uptake were not affected by the alkaloid.Oxidative phosphorylation and the P_i-ATP exchange reaction of phosphorylating beef heart submitochondrial particles were strongly inhibited by spegazzinine (I₅₀, 50 μM) while the ATP-dependent reactions, reduction of NAD⁺ by succinate and the pyridine nucleotides transhydrogenase were less sensitive (I₅₀, 125 μM). Oxygen uptake by submitochondrial particles was not affected.The 2,4-dinitrophenol-stimulated ATPase activity of rat liver mitochondria was not affected by 300 μM spegazzinine, a concentration of alkaloid that completely inhibited phosphorylation. However, higher concentrations of spegazzinine did partially inhibit it. The ATPase activities of submitochondrial particles, insoluble and soluble ATPases were also partially inhibited by high concentrations of spegazzinine.The inhibitory properties of spegazzinine on energy transfer reactions are compared with those of oligomycin, aurovertin and dicyclohexylcarbodiimide. It is concluded that spegazzinine effects are very similar to the effects of aurovertin and that its site of action may be the same or near the site of aurovertin.     

Bishordeninyl terpene alkaloids and other constituents of Zanthoxylum culantrillo and Z. coriaceum

A new alkaloid, culantraramine, has been found in Zanthoxylum culantrillo, and the known alkaloid, alfileramine, has been identified from Z. coriaceum. Both alkaloids are members of a new structural type, bishordeninyl terpenes. Z. culantrillo was also found to contain eudesmin, epieudesmin, hordenine, N-methylisocorydine, magnoflorine, candicine, skimmianine, synephrine, tembetarine and a dihydroxy-dimethoxytetrahydroprotoberberine. Isolated from Z. coriaceum were N-methylisocorydine, dihydrochelerythrine, chelerythrine, N-methylcanadine and aegiline, in addition to alfileramine.     

Biotransformation of reticuline into coreximine,scoulerine, pallidine,and isoboldine with rat liver enzyme

(±)-Reticuline (1) was biotransformed into the protoberberine alkaloids, coreximine (12) and scoulerine (10), the morphinandienone alkaloid, pallidine (14), and the aporphine alkaloid, isoboldine (16). The transformation was stimulated by O₂ and the cofactor NAD, NADP, or NADPH, NADPH being more effective than the other cofactors. The N-methyl group of (±)-reticuline was not incorporated intact into protoberberines.