Four novel gelsedine-type oxindole alkaloids from Gelsemium elegans

Four new gelsedine-type oxindole alkaloids (1-4) were isolated from the leaves and branches of Gelsemium elegans, together with 10 known alkaloids. The structures of the new alkaloids were determined by spectroscopic analyses and partial synthesis from known compounds. Gelsecrotonidine (1), 14-hydroxygelsecrotonidine (2), and 11-methoxygelsecrotonidine (3) possess an additional C₂ unit with an acetic acid residue compared to gelsenicine-related monoterpenoid indole alkaloids. 14-Hydroxygelsedilam (4) is an 18,19-nor-type monoterpenoid indole alkaloid.     

New humantenine-type indole alkaloids with iridoid unit from Gelsemium species

Two new oxindole alkaloids, rankiniridine (1) and humanteniridine (2), having a nitrogen-carbon linkage between a humantenine-type monoterpenoid indole alkaloid and a monoterpene unit with an iridoid skeleton, were isolated from Gelsemium rankinii and Gelsemium elegans, respectively.     

Agelasines O-U, new diterpene alkaloids with a 9-N-methyladenine unit from a marine sponge Agelas sp.

New diterpene alkaloids, agelasines O-U (1-7), have been isolated from an Okinawan marine sponge Agelas sp. The gloss structures and relative stereochemistries of 1-7 were elucidated from the spectroscopic data. Agelasines O-R (1-4) were the third examples of diterpene alkaloid with a 9-N-methyladenine and a pyrrole units. Agelasine O (1) has a halimane skeleton, while agelasines P-R (2-4) have a clerodane skeleton. Agelasines S-U (5-7) were new diterpene alkaloids with a 9-N-methyladenine unit consisting of a halimane skeleton, a labdane skeleton, and a clerodane skeleton, respectively. Agelasines O-R (1-4) and T (6) showed antimicrobial activities against several bacteria and fungi.     

Three new monoterpene indole alkaloids from Psychotria umbellata Thonn.

Three new psychollatine-derived monoterpene indole alkaloids were obtained from Psychotria umbellata Thonn.: 3,4-Dehydro-18,19-β-epoxy-psychollatine (2), N⁴-[1-((R)-2-hydroxypropyl)]-psychollatine (3), and N⁴-[1-((S)-2-hydroxypropyl)]-psychollatine (4). Their structures were determined by ¹H and ¹³C NMR spectra, 2D correlations (COSY, HMQC, and HMBC), and mass and UV spectra. Compounds 3 and 4 were synthesized for structural confirmation and for the determination of the stereochemistry of the hydroxyl group.     

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.     

Aminocadambines A and B, two novel indole alkaloids from Neolamarckia cadamba

Two novel monoterpenoid indole alkaloids, aminocadambines A (1) and B (2), characterized by tetrahydrofuran and 1,2,3,4-tetrahydropyridine rings, were isolated from the leaves of Neolamarckia cadamba. Their structures were elucidated on the basis of spectroscopic and computational methods. The absolute configuration of 1 was established by CD analysis. A plausible biosynthetic pathway for 1 and 2 is proposed.     

Three new sulfur-containing alkaloids, polycarpaurines A, B, and C, from an Indonesian ascidian Polycarpa aurata

Three new sulfur-containing alkaloids, polycarpaurines A (1), B (2), and C (3) were isolated from the tropical ascidian Polycarpa aurata collected in Indonesia, together with six known compounds (4-9). The structures of new compounds were assigned on the basis of their spectral data. Compounds 1, 3, 4, and 8 inhibited colony formation of Chinese hamster V79 cells with EC₅₀ values of 6.8, 8.6, 3.8, and 10 μM, respectively. Compounds 2 and 7 showed modest activity against V79 cells (EC₅₀>10 μM).     

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.     

Voacalgines A–E,new indole alkaloids from Voacanga grandifolia

Five new indole alkaloids, voacalgines A–E (1–5) consisting of a C-mavacurine type of skeleton with 2,3-dihydroxybenzoate moiety, a macroline-type of skeleton, or a macroline-type of skeleton with C₆ unit, were isolated from the bark of Voacanga grandifolia. Their relative structures were determined by means of NMR data. Voacalgine A showed moderate cell growth inhibitory activities against HL-60 and HCT116 cells.     

The alkaloids of the mersinine group: a new subclass of the monoterpenoid indole alkaloids from Kopsia

A total of 16 alkaloids, exemplified by mersinine A and its congeners, and constituting a new subclass of the monoterpenoid indoles, were isolated exclusively and for the first time from Kopsia singapurensis. The structures of these alkaloids were established by spectroscopic methods and in some instances confirmed by X-ray diffraction analysis. A possible biogenetic route from an aspidofractinine precursor is proposed. Compounds 1, 2, 3, 9, and 10 were found to reverse multidrug-resistance in drug-resistant KB cells.     

Lycopladines F and G, new C16N2-type alkaloids with an additional C4N unit from Lycopodium complanatum

Two new Lycopodium alkaloids, lycopladines F (1) and G (2), have been isolated from the club moss Lycopodium complanatum, and the structures and relative stereochemistries of 1 and 2 were elucidated on the basis of spectroscopic data. Lycopladine F (1) is a rare C₁₆N₂-type Lycopodium alkaloid possessing an amino acid residue (C₄N).     

Lyconadins C and F, new Lycopodium alkaloids from Lycopodium complanatum

New Lycopodium alkaloids, lyconadins C (1) and F (2), were isolated from the club moss Lycopodium complanatum. Lyconadin C (1) is a new C₁₆N₂-type Lycopodium alkaloid possessing unique fused-tetracyclic ring system consisting of a cycloheptene ring fused to a decahydroquinoline and pyridone rings. Lyconadin F (2) possesses a primary amide moiety in its molecular, which is the first example of Lycopodium alkaloids. Biogenetically, lyconadins C (1) and F (2) might be related to lyconadins A (4) and B (5). The structures and relative stereochemistry of 1 and 2 were elucidated on the basis of spectroscopic data. The absolute stereochemistry of 2 was elucidated by chemical correlations with lyconadin B (5) through hemiaminal form of lyconadin F (3).     

Alkaloids and citrinins from marine-derived fungus Nigrospora oryzae SCSGAF 0111

A new pyrrolidinone, nigrospine (1), a new indole alkaloid, nigrospin A (2) and two new citrinins, nigrospins B and C (3-4) were isolated from a culture broth of the marine-derived fungal strain Nigrospora oryzae SCSGAF 0111. Their structures were determined by spectroscopic analysis, and the absolute configurations of 1 and 2 were determined by the Mosher ester technique. Compound 1 contains a rare 2,3-dihydro-benzofuran[2,3-c]2-pyrrolidone skeleton.     

New alkaloids sinomacutines A–E,and cephalonine-2-O-β-d-glucopyranoside from rhizomes of Sinomenium acutum

Phytochemical investigation on the rhizomes of Sinomenium acutum led to the isolation of new alkaloids sinomacutines A–E (1–5), and cephalonine-2-O-β-d-glucopyranoside (6), along with known tetrahydroisoquinoline alkaloids (7–9). Among them, sinomacutines A–C were new bistetrahydroisoquinoline alkaloids with morphinane–proaporphine and morphinane–benzyltetrahydroisoquinoline types, and coupled with unique C–CH₂–N unit. Their structures with absolute configuration were elucidated on the basis of 1D and 2D NMR, and ECD spectra analysis. The new compounds were evaluated for their anti-inflammatory and cytotoxic activities, and sallisonine B (2) showed moderate ability to inhibit NO production of LPS-stimulated RAW264.7 macrophages, as well as sallisonine A (1) showed weak inhibitory effects against five cancer cell lines.     

The first enantiospecific total synthesis of a C-quaternary voachalotine alkaloid, (+)-dehydrovoachalotine

The first enantiospecific total synthesis of the indole alkaloid (+)-dehydrovoachalotine (1) has been achieved from d-(+)-tryptophan methyl ester in 28% overall yield. The formation of the prochiral quaternary carbon center at C-16 in the key intermediate (12) was realized via a Tollens reaction from N_a-methylvellosimine (13) in 95% yield. This approach could also be applied to the synthesis of many other indole alkaloids that contain a quaternary carbon center at C(16).     

Complanadine B, obscurumines A and B, new alkaloids from two species of Lycopodium

A new dimer of C₁₆N₂ type alkaloid, complanadine B (1), and two new C₁₆N type alkaloids, obscurumines A (2) and B (3), have been isolated from the club moss Lycopodium complanatum and L. obscurum, respectively. The structures and stereochemistry of 1-3 were elucidated by combination of 2D NMR spectra and chemical transformation. Complanadine A (4) isolated together with 1 induced secretion of neurotrophic factors from human astrocytoma cells.     

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.     

New phlegmarane-type, cernuane-type, and quinolizidine alkaloids from two species of Lycopodium

Two new phlegmarane-type alkaloids, cermizines A (1) and B (2), three new quinolizidine alkaloids, cermizine C (3) and senepodines G (4) and H (5), and a new C₁₆N₂ type alkaloid consisting of a quinolizidine and a piperidine ring, cermizine D (6), as well as two new cernuane-type alkaloids, cernuine N-oxide (7) and lycocernuine N-oxide (8), have been isolated together with cernuine (9) and lycocernuine (10) from the club moss Lycopodium cernuum and L. chinense. The relative stereochemistry of 1-4 and 6, and the absolute stereochemistry of 5, 7, and 8 were elucidated by combination of NOESY correlations, modified Mosher's method, chemical transformations, and computational methods. Cermizine D (6) might be a biosynthetic intermediate of cernuane-type alkaloids such as 7-10.     

To seek an approach toward the chemical conversion of C19-diterpenoid alkaloids to taxoids

This study, as a part of conversion of the C₁₉-diterpenoid alkaloids to the taxoids, described the search of a suitable route to the key intermediate B with four approaches (ABC, ACB, BCA, and CAB) designed and examined. In these cases, a new and efficient approach (CAB) toward the synthesis of the vital intermediates 51 or 52 has been developed. The key steps include the use of a semipinacol rearrangement treatment of 41 with NaOH/DMF under refluxing conditions for 30 min to afford 42, and the rupture of the N-C-19 bond found in 45 or 48 to give 51 or 52, respectively, through NBS imination followed by the creation of the oxaziridine 47 or the nitrone 50 and finally HIO₄ oxidation cleavages.     

Bistabercarpamines A and B,first vobasinyl-chippiine-type bisindole alkaloid from Tabernaemontana corymbosa

Two novel dimeric monoterpene indole alkaloids, bistabercarpamines A (1) and B (2) possessing unprecedented bis-vobasinyl-chippiine-type skeleton, were isolated from the leaves of Tabernaemontana corymbosa. The structures were elucidated on the basis of spectroscopic data, and the absolute configurations of these isolates were determined by CD excition chirality method. Bistabercarpamine A (1) exhibited moderate cell growth inhibitory activity against HepG-2 cells with IC₅₀ of 38.14 ± 1.1 μM.