Chartrenoline,a novel alkaloid isolated from a marine Streptomyces chartreusis NA02069

A novel alkaloid featuring a unique tetracyclic ring system was isolated from a marine actinobacterium.     

Regio- and stereospecific models for the biosynthesis of the indole alkaloids—I : Development of strategic approaches and preliminary experiments

Potential models for both proven and presumed rearrangement processes of indole alkaloid biosynthesis are presented which impute a key role to the reactive dihydropyridine-acrylic ester, dehydrosecodine (19). Plausible mechanisms are considered for the generation of 19 from the Corynanthé-Strychnos alkaloids which lead to several important consequences for both regio- and stereochemical control of the cyclisation of 19 and its close relatives, including the prediction of some hitherto undiscovered classes of indole alkaloid. Preliminary experimental observations are described which indicate the feasibility of generating and utilising dehydrosecodines (as 19) as models for several rearrangement processes of the biosynthetic pathway. A recent criticism of these experiments is analyzed.     

Synthesis of a proposed biosynthetic intermediate of a marine cyclic ether brevisamide for study on biosynthesis of marine ladder-frame polyethers

A monocyclic ether alkaloid, brevisamide (1) was isolated from the dinoflagellate Karenia brevis that produces a variety of ladder-frame polyethers. Its proposed biosynthetic intermediate (2) comprising a linear backbone with an E-olefin functionality was synthesized for biosynthetic studies on the marine ladder-frame polyethers.     

Anti-inflammatory chromone alkaloids and glycoside from Dysoxylum binectariferum

Herein we report isolation of a new chromone alkaloid chrotacumine K (12) from fruits and a chromone glycoside schumaniofioside A (13) from leaves of Dysoxylum binectariferum Hook f. Schumaniofioside A is reported for the first time from Meliaceae family. Other known alkaloids isolated include rohitukine (1) and chrotacumine E (6). The structure of new alkaloid 12 was elucidated on the basis of extensive 1D and 2D NMR analysis, synthesis and chemical hydrolysis. Chemically, chrotacumine K (12) is a 3′-O-acetyl rohitukine which on chemical or enzymatic hydrolysis produces rohitukine. The new alkaloid 12 is also present in seeds and stem-barks of this plant. The glycoside schumaniofioside A (13) is present only in leaves, and in abundance (～1% w/w of dried leaves). The isolated compounds and extracts were evaluated for in vitro effect on the proinflammatory cytokines (TNF-α and IL-6) in human monocytic THP-1 cells. The alkaloid 12 displayed potent inhibition (57%) of TNF-α at 0.3 µM, and was non-toxic to THP-1 cells up to 40 µM, indicating its excellent therapeutic window. Furthermore, a nitrobenzoyl ester analog 15e showed better inhibition of IL-6 than parent natural product chrotacumine K.     

Isatindigodiphindoside,an alkaloid glycoside with a new diphenylpropylindole skeleton from the root of Isatis indigotica

A novel indole alkaloid glycoside with an unprecedented 2-(diphenylpropyl)-indole skeleton, isatindigodiphindoside (1), was isolated from an aqueous extract of the roots of Isatis indigotica. The structure was determined by extensive spectroscopic studies, especially by 2D NMR data analysis combined with enzymatic hydrolysis and ECD calculations. Plausible biosynthetic pathways of compound 1 are also discussed.     

Campylopin from Delphinium campylocentrum, the first hetidane C20-diterpene, suggests a new alkaloid biogenetic pathway

A novel C₂₀-diterpene, campylopin (1), was isolated from the whole herb of Delphinium campylocentrum. The elucidation of its structure was accomplished through extensive spectroscopic methods. Compound 1 represents the first hetidane-type diterpene skeleton, which may imply a new biosynthetic pathway from the atisane or hetidane-type diterpene to the hetidine-type diterpenoid alkaloid.     

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.     

First total synthesis of isoquinolinone alkaloid marinamide and its methyl ester

The first total synthesis of isoquinolinone alkaloid marinamide 1 and its methyl ester 2 was described. The key steps involved a regioselective Frieclel-Crafts reaction of 1-benzyl-1H-pyrrole to form the intermediate 8.     

A New Route to Pyrrolidines: One-Step Cyclization of 1,4-Azido Alcohol Synthesis of 1,4-Dideoxy-1,4-Imino-L-Lyxitol

Several optically active 3,4-dihydroxy-2-hydroxymethyl pyrrolidines are potent α-glycosidase inhibitors; for example, 1,4-dideoxy-1,4-imino-D-lyxitol (1) is a powerful inhibitor of α-galactosidase.¹ Furthermore, pyrrolidine 1 can be easily converted into the indolizidine alkaloid swainsonine to which it is structurally related.² (-) Swainsonine exhibits α-D-mannosidase inhibitory activity and immunoregulatory activity. Certain swainsonine stereoisomers have glycosidase inhibitory activity as well, and therefore have attracted considerable interest.³ 1,4-Dideoxy-1,4-imino-L-lyxitol (2) (enantiomer of 1) could be of biological interest. This communication describes the first synthesis of 2, starting from D-ribonolactone.     

Myrioneurinol: a novel alkaloid skeleton from Myrioneuron nutans

A new alkaloid, myrioneurinol (1), was isolated from the leaves of Myrioneuron nutans and its structure determined from spectral analysis, including mass spectrometry and 2D NMR. Myrioneurinol (1) presented an unprecedented fused tetracyclic skeleton. The absolute configuration was established by the modified Mosher's method, using (R)- and (S)-9-anthrylmethoxyacetic acid (9-AMAA). A plausible biosynthetic pathway starting from l-lysine via Δ-piperideine was proposed for 1 in comparison with nitraramine biosynthesis and related alkaloids.     

Biomimetic approach to communesin B (a.k.a. nomofungin)

The development of an approach to the alkaloid communesin B (2) is presented. The approach is based on considerations of a possible biosynthetic sequence involving an oxidative coupling of tryptamine with a derivative of the ergot alkaloid aurantioclavine. Structure revision is also suggested for the recently isolated microfilament disrupting alkaloid nomofungin.     

Further applications of endocyclic enamine-enone annulations : The total syntheses of rac-Sceletium alkaloid A4 and 3'-demethoxy sceletium alkaloid A4

The total synthesis of rac-sceletium alkaloid A₄1a and of its 3'-demethoxy analogue 1b via the annulation of endocyclic enamines 4a–b is presented. The Michael acceptor 5a is a useful synthon for the two-step synthesis of 2,3-disubstituted pyridines from Δ²-pyrrolines.     

Penioxalamine A,a novel prenylated spiro-oxindole alkaloid from Penicillium oxalicum TW01-1

Penioxalamine A (1), a novel prenylated spiro-oxindole alkaloid having a unique seven-membered nitrogen heterocycle system, was isolated from the fungus Penicillium oxalicum TW01-1. The structure of 1 was elucidated on the basis of the spectral data, single-crystal X-ray diffraction, and CD analysis. Compound 1 showed moderate cytotoxicity against HL-60 cell line. The possible biosynthetic pathway of 1 was also proposed.     

Mechanism of alkaloid cyclopeptide synthesis in the ergot fungus Claviceps purpurea

Background: Previous analyses of the biosynthesis of the alkaloid cyclopeptides from the ergot fungus Claviceps purpurea were hampered by a lack of suitable systems for study in vitro, and this led to conflicting results concerning the mechanism of alkaloid cyclopeptide formation. Recently, D-lysergyl peptide synthetase (LPS) of the ergot fungus Claviceps purpurea, which assembles the non-cyclol precursors of the ergopeptines, has been partially purified and shown to consist of two polypeptide chains of 370 kDa (LPS 1) and 140 kDa (LPS 2); these contain all the sites necessary for the assembly of the D-lysergyl peptide backbone. The mechanism of D-lysergyl peptide synthesis remained unclear, however.Results: We have identified the obligatory peptidic intermediates in d-lysergyl peptide synthesis and the sequential order of their formation. The two LPS subunits catalyze the formation of d-lysergyl mono-, di-, and tripeptides as enzyme-thioester intermediates, the formation of which appears to be irreversible. Peptide synthesis starts when d-lysergic acid binds to the LPS 2 subunit, which most probably occurs after the previous round of synthesis has been completed by the release of the end product from the LPS enzyme.Conclusions: We have shown that the mechanism of d-lysergyl peptide synthesis is an ordered process of successive acyl transfers on a multienzyme complex. This knowledge opens the way for enzymatic and genetic investigations into the formation of novel alkaloid cyclopeptides.     

Total synthesis of α-yohimbine

A facile total synthesis of the indole alkaloid α-yohimbine (1) from the hydroisoquinoline derivative 5 has been completed.     

Gelegamines A-E: five new oxindole alkaloids from Gelsemium elegans

Five new oxindole alkaloids, gelegamines A-E (1-5), were isolated from the roots of Gelsemium elegans. Their structures were extensively elucidated on the basis of spectroscopic analysis. Among them, the epoxy ring (C-19/C-20) of gelegamine A (1) was assigned as α-orientation by ROESY experiment and DFT method at B3LYP/6-31g(d) level, and gelegamine B (2) is the first humantenine-type alkaloid with 19-(E) ethylidene configuration. The absolute configurations of gelegamines A-E (1-5) were established on biosynthetic consideration coupled with CD experiments.     

Isolation of indole alkaloid and anthranilic acid derivatives from Indigo Pulverata Levis

A new indole alkaloid, pulveratinol (1), and two new anthranilic acid derivatives (2 and 3) were isolated from Indigo Pulverata Levis, together with 12 known compounds (4–15). The structures of the new compounds (1–3) were determined through spectroscopic methods. The absolute configuration of 1 was confirmed further by electronic circular dichroism (ECD) data analysis and computational method with advanced statistics (DP4). All isolated compounds (1–15) were evaluated for their potential neuroprotective effects through induction of nerve growth factor (NGF) in C6 glioma cells.     

The directed metalation connection to aryl-aryl cross coupling.Regiospecific synthesis of phenanthridines,phenanthridinones and the biphenyl alkaloid ismine

Concise general routes to phenanthridines 4 and phenanthridinones 5 based on directed ortho metalation and cross coupling tactics are described; a short synthesis of the Amaryllidaceae alkaloid ismine (8b) is reported.     

seco-Polycyclic polyprenylated acylphloroglucinols with unusual carbon skeletons from Hypericum ascyron

Three new seco-polycyclic polyprenylated acylphloroglucinols (PPAPs), ascyronones A–C (1–3), and a new biosynthetic precursor, ascyronone D (4), were isolated from Hypericum ascyron together with three known analogues (5–7). Compounds 1 and 2, sharing an unusual seven-membered carbon core fused with a γ-lactone ring, could be derived from 1,9-seco-PPAPs via further rearrangement. A biomimetic transformation from 5 to 1 was performed by using base-driven retro-Claisen and rearrangement cascade reaction, which further confirmed the structure of 1 and shed light to its possible biosynthetic pathway. Interestingly, all these compounds are decorated with a methyl group at C-5 instead of a prenyl or geranyl group in many other PPAPs. The isolates were evaluated for their inhibitory activities against five human tumor cell lines.     

Palladium catalyzed insertion of carbon monoxide into benzyl-tetrahydroisoquinolines : A new synthesis of berbine alkaloids

A new total synthesis of the berbine alkaloid ring system has been achieved. Palladium catalyzed insertion of carbon monoxide into the 1 - (2 - bromobenzyl) - substituted - 1,2,3,4 - tetrahydroisoquinolines (1a–1d) by the use of catalytic amounts of palladium diacetate and triphenylphosphine in the presence of tri-n-butylamine afforded the berbin-8-ones (2a–2d) which, on reduction with lithium aluminium hydride gave the berbines (±)-berbine 3a, (±)2,3-dimethoxyberbine 3b, (±)-xylopinine 3c and (±)-pseudoepitetrahydroberbine 3d.