Biphenyl quinolizidine lactone alkaloids from “sinicuichi” (Heimia salicifolia)

Six new biphenyl quinolizidine lactone alkaloids: 14α-hydroxydecodine (1), 14β-hydroxydecodine (2), 4″-O-demethylheimidine (3), 4″-O-demethyl-9β-hydroxyvertine (4), 4″-O-demethylvertine N-oxide (5), and 4″-O-demethyl-9β-hydroxyvertine N-oxide (6) were isolated from so-called “sinicuichi” (origin: Heimia salicifolia) together with 18 known alkaloids. Their structures were determined by spectroscopic analyses and chemical conversions.     

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.     

Enantioselective synthesis of some tetrahydroisoquinoline and tetrahydro-β-carboline alkaloids

Four alkaloids: (R)-(+)-cryspine A 5, (R)-(+)-octahydroindolo[2,3-a]quinolizidine 8, (R)-(+)-harmicine 19 and (R)-(+)-desbromoarborescidine 22 were prepared via the asymmetric transfer hydrogenation reaction of a prochiral enamine (iminium salt). The enantiomeric excesses of the isolated alkaloids were determined from their ¹H NMR spectra measured in the presence of (+)-(R)-tert-butylphenylphosphinothio(seleno)ic acids as chiral solvating agents. The absolute configurations at the newly created stereogenic carbon atoms were confirmed, in all cases, by X-ray crystallography.     

New quinolizidine and diaza-adamantane alkaloids from Acosmium dasycarpum (Vog.) Yakovlev—Fabaceae

The phytochemical investigation of the methanol crude extract obtained from Acosmium dasycarpum (Vog.) Yakovlev root bark led to the isolation of the quinolizidine alkaloids lupanine, acosmine, acosminine and lupanacosmine, as well as the diaza-adamantane alkaloids panacosmine and dasycarpumine. Lupanacosmine (4) and dasycarpumine (6) have been described for the first time herein.     

Senepodines B-E, new C22N2 alkaloids from Lycopodium chinense

Four new C₂₂N₂Lycopodium alkaloids, senepodines B-E (2-5), consisting of an octahydroquinoline ring and a quinolizidine ring have been isolated together with senepodine A (1) from the club moss Lycopodium chinense. The relative and absolute stereochemistry of 2-5 were determined by combination of NOESY correlations and chemical transformation, while the absolute configuration of 1 was assigned by exciton chirality method.     

Organocatalytic enantioselective synthesis of quinolizidine alkaloids (+)-myrtine, (−)-lupinine, and (+)-epiepiquinamide

The organocatalytic synthesis of quinolizidine alkaloids (+)-myrtine, (−)-lupinine, and (+)-epiepiquinamide is described. It involved, as the key step, an enantioselective intramolecular aza-Michael reaction (IMAMR) catalyzed by Jørgensen catalyst I, affording the common precursor with high enantioselectivity. This compound was subsequently transformed into the three alkaloids in a highly diastereoselective manner.     

Lycochinines A-C, novel C27N3 alkaloids from Lycopodiumchinense

Three novel C₂₇N₃-type Lycopodium alkaloids, lycochinines A-C (1-3) consisting of an octahydroquinoline or a decahydroquinoline, a quinolizidine, and a piperidine, were isolated from the club moss Lycopodium chinense. The relative stereochemistry of 1-3 was determined by a combination of NOESY correlations and chemical transformations.     

Alkaloids from the roots of Stemona tuberosa and their anti-tobacco mosaic virus activities

Stemtuberlines A (1) and B (2), two new alkaloids with a unique tricyclic pyrrolo [3,2,1-jk]benzazepine-12-one nucleus, three new croomine-type alkaloids, stemtuberlines C-E (3–5), together with seven known ones were isolated from the roots of Stemona tuberosa. The structures of the new alkaloids were elucidated based on a comprehensive spectroscopic data analysis. The absolute configurations of 1 and 2 were determined by quantum ECD calculations. The anti-tobacco mosaic virus activity of the Stemona alkaloids was firstly evaluated and compound 11 exhibited significant anti-tobacco mosaic virus activity with the curative inhibition rate of 84.6% at concentration of 50?μg/mL.     

Cage-like monoterpenoid indole alkaloids with antimicrobial activity from Alstonia scholaris

Three new cage-like monoterpenoid indole alkaloids, scholarisines T–V (1–3), together with three known analogues 4–6 were isolated from the leaves of Alstonia scholaris. Among them, 2 represents a unique degraded derivative, whereas 3 shares a rare 5,16-seco lactone scaffold. The structures were mainly established by extensive spectroscopic data analyses, and their plausible biosynthesis pathway from picrinine were proposed. Compared with positive control cefotaxime, alkaloid 2 showed remarkable antibacterial activity against Bacillus subtilis with an MIC value of 3.12?μg/mL, whereas 1–3 exhibited significant antibacterial effects on Escherichia coli with an MIC value of 0.78?μg/mL.     

Novel quinolinone alkaloids bearing a lignoid moiety and related constituents in the leaves of Melicope denhamii

Six novel quinolinone alkaloids bearing a phenylpropanoid or a coumarin moiety, named melicodenines C–H (1–6), two new cinnamyl alcohol derivatives, named melicodins A (7) and B (8), and a new coumarinolignan, named melicodin C (9), were isolated from the leaves of Melicope denhamii (Seem.) T. G. Hartley. Their structures were established by spectroscopic analyses including extensive 2D-NMR experiments. Compounds 1–5 and 9 possess a cyclobutane ring and are hypothetically produced by a [2+2] cycloaddition, whereas compound 6 is presumed to form through a Diels–Alder cycloaddition followed by the elimination of an acetone molecule. Ten quinolinone alkaloids (1–6, 10–13) and a coumarinolignan (9) were tested for anti-proliferative activity against DLD-1 human colon cancer cells. Melicodenine G (5) showed the most potent inhibitory activity, causing the induction of apoptosis with an IC₅₀ value of 9.4±0.3 μM.     

Prenylated indole alkaloids and chromone derivatives from the fungus Penicillium sp. SCSIO041218

Four new prenylated indole alkaloids (1–4), and four new chromone derivatives (7–10), together with six known compounds (5, 6, and 11–14), have been isolated from the mangrove sediment derived fungus Penicillium sp. SCSIO041218, cultured in the 1% NaCl PDB substrate. The structures of new compounds were determined by analysis of the NMR and MS spectroscopic data. The absolute configuration of the prenylated indole alkaloids were elucidated based on the comparison of ECDs with known analogues. The absolute configurations of the chromone derivatives were determined by time-dependent density functional theory calculations of the ECD spectra. In all of these isolated compounds, penixanthones A and B (12 and 13) exhibited antiallergic activities in vitro.     

Lycogladines A-H,fawcettimine-type Lycopodium alkaloids from Lycopodium complanatum var. glaucum Ching

Five new fawcettimine-type alkaloids (1–5) and three new natural products (6–8), along with four known analogues, fawcettimine (9), fewcettidine (10), lycopoclavamine B (11), and lycopladine B (12), were isolated from the whole plant of Lycopodium complanatum var. glaucum Ching. The structures of lycogladines A-H (1–8) were determined based on HRESIMS, 1D and 2D NMR spectroscopic analysis, as well as single-crystal X-ray diffraction. Compound 1 possesses a new ring system that is formed through the linkage of C-13-OC-2, which is rarely present in Lycopodium alkaloids (LAs). Compounds 1–8 were tested for their β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) and acetylcholinesterase (AChE) inhibitory activities.     

A general strategy for the formal synthesis of (−)-trans-kumausyne and total synthesis of (5R)-Hagen’s gland lactones from diacetone-d-glucose

A general strategy for the formal synthesis of (−)-trans-kumausyne 1 via the bicyclic lactone (3aR,5R,6aR)-4 and total synthesis of (5R)-Hagen’s gland lactones 2 and 3 via bicyclic lactone (3aR,5S,6aR)-5 starting from diacetone-d-glucose 6 is described. Syntheses of 4 and 5 were achieved by Wittig olefination–lactonization–Michael addition of the corresponding lactols 16 and 17, respectively.     

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.     

Pyranoside phosphite–phosphoroamidite ligands for Pd-catalyzed asymmetric allylic alkylation reactions

We have designed and synthesized a new family of readily available phosphite–phosphoroamidite ligands for Pd-catalyzed allylic substitution reactions of several substrates with different steric and electronic properties. These ligands are derived from d-glucosamine and contain several substituents in the biphenyl moieties, with different steric and electronic properties. Systematic variation of the ligand parameters indicates that enantioselectivities are mainly affected by the substituents at the para-positions of the biphenyl moieties. Enantiomeric excesses of up to 89% with high activities were obtained for rac-1,3-diphenyl-3-acetoxyprop-1-ene S1, rac-(E)-ethyl-2,5-dimethyl-3-hex-4-enylcarbonate S2 and rac-3-acetoxycycloheptene S5.     

New nitro-benzo[c]phenanthridine and indolopyridoquinazoline alkaloids from Zanthoxylum atchoum

The first phytochemical investigation of the roots of Zanthoxylum atchoum has led to the isolation of two new nitro-benzo[c]phenanthridine alkaloids 6-nitronitidine (1) and 6-nitro-8-methoxy-7,8-dihydronitidine (2), two new salts of indolopyridoquinazoline alkaloids 3-hydroxy-8,13-dihydro-14-methyl-5-oxo-7H-indolo[2’,3’:3,4]pyrido[2,1-b]quinazolin-14-ium (3) and its zwitterionic form 3-phenolate-8,13-dihydro-14-methyl-5-oxo-7H-indolo[2’,3’:3,4]pyrido[2,1-b]quinazolin-14-ium (4) along with 18 (5–22) known compounds. Their chemical structures were elucidated by spectroscopic analysis including 1D and 2D NMR and MS techniques. This is the first report of the nitro group on the biosynthesis of the natural benzo[c]phenantridine alkaloids. Compound 2 exhibited potent antibacterial activity against Staphylococcus aureus of MIC₅₀ = 4 μg·mL⁻¹.     

Preparation of optically active bridged biphenyls via a stereoselective synthesis of their mono (tricarbonylchromium) complexes. Chiroptical properties and absolute chiralities of the complexes and ligands12

Reaction of the mono(tricarbonylchromium) complex 3 of diphenic acid anhydride with chiral amines gave the optically active imides 9-11. 10 and 11, from (S)-(?) and (R)(+)-phenylalaninol, respectively were separated by chromatography into exo- and endo-diastereomers (a and b) with opposite metallocene chiralities but with the same axial chirality. The (S)-(?) amino-alcohol induces (S)_a-chirality and vice versa. The absolute configurations of the metallocene and axial-chiral parts of the biphenyl system were deduced from the circular dichroism spectra, the former [(R)_m or (S)_m] by comparison with the CD of benchrotrenes of known absolute configuration, the latter [(R)_a or (S)_a] by applying the exciton model of coupled oscillators to the optically stable biphenyl ligands [i.e. the imides (?)- and (+)-8 easily accessible from 10 and 11 by photochemical decomplexation]. (R)_m-(S)_a for the complex (+)-10a (exo) and (S)_m-(S)_a for the endo-isomer (?)-10b, and vice versa for the complex 11. The parent ligands have the configurations (S)_a(?)-8 and (R)_a(+)-8, respectively.Photochemical cleavage of the optically active bis(tricarbonylchromium) complex (?)-13 of the biphenyl lactone 12 at ?60°C afforded optically labile 12 with a half-life time of racemization of ca 10 min at ?20°. On the basis of its CD the configuration (R)_a is tentatively proposed for 12.The work described represents the first example of the preparation of optically-active biphenyls via benchrotrene precursors.     

Synthesis of trihydroxy quinolizidine alkaloids: 1,3-addition reaction of allylmagnesium bromide to a sugar nitrone

The synthesis of (1R,2R,3S,9aR) and (1R,2R,3S,9aS) trihydroxy quinolizidine alkaloids 3a and 3b from d-glucose derived nitrone 4 is described. The key transformation involves the 1,3-addition of allylmagnesium bromide to nitrone 4 that afforded high diastereoselectivity in the presence of TMSOTf. The N-O bond reductive cleavage, N-Cbz protection, ozonolysis, Wittig olefination, lactum formation and reductive amination cascade afforded the target compounds 3a and 3b in good overall yield.     

Synthesis of Diels–Alder adducts of the quinolizidine alkaloids N-methylcytisine, (−)-leontidine,and (−)-thermopsine with N-phenylmaleimide

The Diels–Alder adducts of the quinolizidine alkaloids N-methylcytisine, (?)-leontidine, and (?)-thermopsine with N-phenylmaleimide have been synthesized. The structures and absolute configurations of the new asymmetric centers of the products were determined by NMR spectroscopy experiments, QC-calculations, and X-ray data.     

Cyclopeptide alkaloids of Zizyphus oenoplia

The known alkaloids zizyphine-A (1) and -B (2), abyssinine-A (4) and -B (5), and the previously undescribed zizyphine-C (3), -D (6) and -E (7) have been isolated from the stem bark of Zizyphus oenoplia. The structures of the new compounds were elucidated by spectroscopic methods applied to the alkaloids and to some of their transformation products, and by chemical degradation reactions.