Isolation,characterization, and NMR spectroscopic data of indole and oxindole alkaloids from Mitragyna speciosa

A new indole alkaloid, 7β-hydroxy-7H-mitraciliatine (1) and a new oxindole alkaloid, isospeciofoleine (2) together with nine known alkaloids were isolated from Mitragyna speciosa and characterized by NMR, CD, and MS spectroscopic data analyses. The ¹H and ¹³C NMR spectroscopic data of isospeciofoline (3), isorotundifoline (4), paynantheine (5), and 3-isopaynantheine (6) were also reported for the first time.     

A novel approach to the taxane ABC ring system through chemical conversion from C19-diterpenoid alkaloid deltaline

A novel approach to the highly functionalized taxane ABC ring system through chemical conversion of the C₁₉-diterpenoid alkaloid deltaline (1) was achieved in six steps (1→17) in 18% overall yield mainly by Grob fragmentation, fission of the Δ⁹⁽¹⁴⁾ double bond, followed by aldol condensation, and Pelletier's cleavage process.     

Vincamajorines A and B,monoterpenoid indole alkaloids with new carbon skeletons from Vinca major

Two new monoterpenoid indole alkaloids, vincamajorines A (1) and B (2), were isolated from Vinca major. Their structures were elucidated by means of 1D and 2D NMR, and HREIMS spectroscopic data. The relative and absolute configurations were deduced by comparing the experimental ¹³C NMR, ECD spectra, and OR data with those theoretically calculated. Vincamajorine A (1) represents a new C₂₀ carbon skeleton arranged compactly in seven rings, and vincamajorine B (2) is an alkaloid with an unprecedented 6/5/7/5/6 pentacyclic ring system. A possible biosynthetic pathway was also proposed for the formation of 1 and 2.     

Hyrtimomines,indole alkaloids from Okinawan marine sponges Hyrtios spp.

Six new indole alkaloids, hyrtimomines F–K (1–6), were isolated from Okinawan marine sponges Hyrtios spp. The structures of 1–6 were elucidated on the basis of spectroscopic analysis. Hyrtimomine F (1) is a structurally unique bisindole alkaloid possessing an α-keto-?-caprolactam ring, while hyrtimomine G (2) is a symmetrical bisindole alkaloid. Hyrtimomines H–K (3–6) are indole alkaloids possessing β-carboline skeleton with an imidazolium unit. Antimicrobial activities of hyrtimomines F–K (1–6) were evaluated.     

Nagelamides M and N, new bromopyrrole alkaloids from sponge Agelas species

Two new bromopyrrole alkaloids, nagelamides M (1) and N (2), have been isolated from an Okinawan marine sponge Agelas species, and the structures and stereochemistry were elucidated from the spectroscopic data. Nagelamide M (1) is a novel bromopyrrole alkaloid possessing a 2-amino-octahydropyrrolo[2,3-d]imidazole ring with a taurine unit, while nagelamide N (2) is a new bromopyrrole alkaloid possessing a 2-amino-tetrahydroimidazole-4-one ring with a taurine unit and 3-(dibromopyrrole-2-carboxamido)propanoic acid moiety. Nagelamides M (1) and N (2) exhibited antimicrobial activity.     

Novel alkaloids, paxdaphnines A and B with unprecedented skeletons from the seeds of Daphniphyllum paxianum

Two novel Daphniphyllum alkaloids with unprecedented skeletons, namely paxdaphnines A (1) and B (2), have been isolated from the seeds of Daphniphyllum paxianum. Paxdaphnine A (1) is a 19-nor-Daphniphyllum alkaloid with highly caged skeleton, and paxdaphnine B (2) is the first 1,19-bisnor-Daphniphyllum alkaloid. The relative structures of 1 and 2 were elucidated by spectral methods, and their unique biosynthetic pathway postulated. The absolute structure of 1 was determined by X-ray diffraction of the iodide derivative (1a) of 1, and the absolute stereochemistry of 2 was proposed by correlation with the biosynthetic pathway for 1.     

Mekongenines A and B, two new alkaloids from Bousigonia mekongensis

Mekongenine A (1) possessing an unprecedented structure constituted from the union of a rare 2,7-seco eburnamine half and an aspidospermine alkaloid, together with a new bisindole alkaloid, mekongenine B (2), consisting of an eburnamine-aspidospermine type skeleton, was isolated from Bousigonia mekongensis. Their structures were elucidated by means of spectroscopic methods and those of 2 were further confirmed by X-ray diffraction. The absolute configurations of 1 and 2 were determined by comparison of quantum chemical TDDFT calculated and experimental ECD spectra. Mekongenines A (1) and B (2) exhibited cell growth inhibitory activities against various human cancer cell lines.     

Spectroscopic analyses and chemical transformation for structure elucidation of two novel indole alkaloids from Gelsemium elegans

Two new monoterpenoid oxindole alkaloids, gelsevanillidine (1) having an additional vanillin residue on gelsenicine-type alkaloid and gelseoxazolidinine (2) possessing an unusual oxazolidine ring, were isolated from Gelsemium elegans. To confirm their structures, the chemical transformation of a humantenine-type alkaloid into gelsevanillidine (1) and the deacetoxy derivative of gelseoxazolidinine was performed.     

Indole alkaloids from Kopsia jasminiflora

Seven new indole alkaloids (aspidofractinine type 1–3, kopsine type 5, strychnos type 6, and vincamine type 7, 8) were isolated from Kopsia jasminiflora (Apocynaceae) collected in Thailand. 5-Oxokopsinic acid (4) was isolated from nature for the first time. The structures of the new alkaloids were determined by spectroscopic analyses and chemical transformation of a known alkaloid. 5,6-Secokopsinine (1) possesses a dialdehyde function that is formed by oxidative cleavage of the C-5–C-6 bond of kopsinine (9). New vincamine-type alkaloid 8 showed potent inhibitory activity toward human cancer cell lines (A549, HT29, HCT116).     

Marine bacterial inhibitors from the sponge-derived fungus Aspergillus sp.

Chromatographic separation of a crude extract obtained from the fungus Aspergillus sp., isolated from the Mediterranean sponge Tethya aurantium, yielded a new tryptophan derived alkaloid, 3-((1-hydroxy-3-(2-methylbut-3-en-2-yl)-2-oxoindolin-3-yl)methyl)-1-methyl-3,4-dihydrobenzo[e][1,4]diazepine-2,5-dione (1), and a new meroterpenoid, austalide R (2), together with three known compounds (3–5). The structures of the new compounds were unambiguously elucidated on the basis of extensive one and two-dimensional NMR (¹H, ¹³C, COSY, HMBC, and ROESY) and mass spectral analysis. Interestingly, the compounds exhibited antibacterial activity when tested against a panel of marine bacteria, with 1 selectively inhibiting Vibrio species and 2 showing a broad spectrum of activity. In contrast, no significant activity was observed against terrestrial bacterial strains and the murine cancer cell line L5178Y.     

Total synthesis of a dibromotyrosine alkaloid inhibitor of mycothiol S-conjugate amidase

Two complementary synthetic sequences are described for the first total synthesis of a dibromotyrosine alkaloid (1) reported to inhibit a critical mycobacterial enzyme, mycothiol S-conjugate amidase. The O-benzyloxime of 4-hydroxyphenylpyruvic acid was dibrominated and successively linked to a 3-aminopropyl chain, then to a 4-aminobutylguanidine unit, followed by selective deprotections to yield alkaloid 1. In an improved variant, the O-tetrahydropyranyloxime 12 was condensed with 4-aminobutylguanidine then dibrominated to phenol 14, which upon Mitsunobu coupling to a 3-aminopropyl segment and deprotection produced the target 1.     

New oxindole and indole alkaloids from Gelsemium rankinii

Six new humantenine-type (1-6) and two new gelsemine-type (7, 8) oxindole alkaloids and one new indole alkaloid (9) were isolated from the leaves and branches of Gelsemium rankinii. The structures of the new alkaloids were determined by spectroscopic analyses. Among them, 6-hydroxyhumantenine (5) is the first example of a Gelsemium alkaloid with an oxygen function at C-6 position, and is a plausible biogenetic precursor of gelsemine-type alkaloids.     

Pseudoceratinazole A: a novel bromotyrosine alkaloid from the Australian sponge Pseudoceratina sp.

Mass-directed fractionation based on a Trypanosoma brucei brucei active fraction from the Australian sponge Pseudoceratina sp. led to the isolation of a novel bromotyrosine alkaloid, pseudoceratinazole A (1). Compound 1 is the first dimeric bromotyrosine alkaloid containing an imidazole-bridging moiety.     

Orthidines A-E, tubastrine, 3,4-dimethoxyphenethyl-β-guanidine, and 1,14-sperminedihomovanillamide: potential anti-inflammatory alkaloids isolated from the New Zealand ascidian Aplidium orthium that act as inhibitors of neutrophil respiratory burst

In addition to the known dihydroxystyrylguanidine alkaloid tubastrine (1), five new dimers, orthidines A-E (2-6) and the biosynthetically unrelated 1,14-sperminedihomovanillamide (orthidine F, 7) were isolated from the New Zealand ascidian Aplidium orthium. The structures of the new compounds, elucidated by interpretation of spectroscopic data, encompass benzodioxane neolignan-type scaffolds (2-5) and a 1,2,3,4-tetrasubstituted cyclobutane (6), the latter likely having arisen via [_π2_s+_π2_s] dimerization of tubastrine. The subunit head-to-tail orientation of dimer 6 was established unambiguously by interpretation of data from a ²J,³J-HMBC NMR experiment. The structure of 7 was also confirmed by facile synthesis. Compounds 1-4, 6, and 7 inhibited the in vitro production of superoxide by PMA-stimulated human neutrophils in a dose-dependent manner with IC₅₀s of 10-36 μM and this was associated with inhibition of superoxide production by neutrophils in vivo in a murine model of gouty inflammation.     

Plakoridine C, a novel piperidine alkaloid from an Okinawan marine sponge Plakortis sp.

A new piperidine alkaloid plakoridine C (1) has been isolated from an Okinawan marine sponge Plakortis species, and the structure was elucidated from spectroscopic data. Plakoridine C (1) is a new alkaloid possessing a piperidine ring connected to a β-keto-γ-lactone through a double bond.     

Zamamidine C, 3,4-dihydro-6-hydroxy-10,11-epoxymanzamine A, and 3,4-dihydromanzamine J N-oxide, new manzamine alkaloids from sponge Amphimedon sp.

New manzamine alkaloids, zamamidine C (1), 3,4-dihydro-6-hydroxy-10,11-epoxymanzamine A (2), and 3,4-dihydromanzamine J N-oxide (3), have been isolated from an Okinawan marine sponge Amphimedon species. The structures and stereochemistries of 1-3 were elucidated from the spectroscopic data and chemical derivatization. Zamamidine C (1) is a new manzamine alkaloid possessing a second β-carboline ring via an ethylene unit at N-2 of manzamine D, while 3,4-dihydro-6-hydroxy-10,11-epoxymanzamine A (2) is the first manzamine alkaloid possessing an epoxide ring at C-10 and C-11. Zamamidine C (1) showed significant antitrypanosomal activity against Trypanosoma brucei brucei, the parasite associated with sleeping sickness, and antimalarial activity against Plasmodium falciparum, the causative agent of malaria in vitro.     

Daphlongeramine A, novel Daphniphyllum alkaloid from Daphniphyllum longeracemosum

A novel Daphyniphyllum alkaloid, Daphlongeramine A (1) with a unique fused octacyclic skeleton, together with a quite recently reported alkaloid Paxdaphnine A (2), were isolated from the fruits of Daphniphyllum longeracemosum. The structures were elucidated on the basis of spectroscopic data.     

Synthesis of bacillamide 3 and its analogue

The bacillamide 1 is a new algaecide from the marine bacterium Bacillus sp. SY-1. Its analogues bacillamide 3 and alkaloid 4 were firstly synthesized effectively from d-alanine. The key step was a coupling reaction via the mixed anhydride. All structures were confirmed by ¹H NMR and ¹³C NMR. The final compounds were confirmed by ¹H NMR, ¹³C NMR and HRMS and the results are consistent with the reported natural products.     

Ophiuroidine, the first indolo[2,1-b]quinazoline alkaloid from the Caribbean brittle star Ophiocoma riisei

A new indoloquinazoline alkaloid, ophiuroidine 1, having an indolo[2,1-b]quinazoline-6,12-dione skeleton, was isolated from the Caribbean ophiuroid, Ophiocoma riisei. The structure of 1 was determined as 4,8,9-trihydroxyindolo[2,1-b]quinazoline-6,12-dione from spectroscopic data. Ophiuroidine 1 is the first example of an indoloquinazoline alkaloid found in a marine invertebrate.     

Two novel indole alkaloids, Kopsiyunnanines A and B, from a Yunnan Kopsia

Two novel indole alkaloids having unusual skeletons were isolated from the aerial part of Yunnan Kopsia arborea. Kopsiyunnanine A (1) is a new class of bisindole alkaloid composed of vallesiachotamine (modified Corynanthe-type) and Aspidospermatan-type alkaloids. Kopsiyunnanine B (2) is a new Corynanthe-type oxindole alkaloid rearranged by D ring rotation.