Alkaloid production by callous tissue cultures of Cereus peruvianus (Cactaceae)

The morphologically undifferentiated cells of nonregenerant callous tissue of Cereus peruvianus cultured in the original medium and in medium supplemented with tyrosine were used as an alkaloid source. Comparison of alkaloid production by C. peruvianus plants and by callous tissues indicated that alkaloid levels were almost twice as high in callous tissues as in shoots of C. peruvianus plants. The ratio of alkaloid concentration between mature plant and morphologically und ifferentiated cells of callous tissue was 1∶1.7. A relationship between culture medium containing tyrosine and alkaloid production was also observed in the callous tissues of C. peruvianus. Since increased alkaloid production may be induced by additional factors such as tyrosine, increasing levels of tyrosine or other conditions of the culture medium may be considered factors for inducing higher alkaloid production by C. peruvianus callous tissues.     

Alkaloidal variation in cissampelos capensis (Menispermaceae)

Cissampelos capensis, commonly known by the Afrikaans name "dawidjies" or "dawidjieswortel", is the most important and best known medicinal plant of the family Menispermaceae used by the Khoisan and other rural people in the western region of South Africa. The main alkaloids in the leaves, stems and rhizomes were isolated and identified. Several of the main compounds were previously found in species of the related genus Antizoma and this similarity indicates that the two genera are closely related if not congeneric. Bulbocapnine (an aporphine alkaloid), dicentrine (an aporphine alkaloid) and salutaridine (a morphinane alkaloid) were the main alkaloids in the leaves, while bulbocapnine, cissacapine, cycleanine and insularine (the last three are bisbenzyltetrahydro-isoquinoline alkaloids) are the major compounds in the stems. The rhizome contains mostly bisbenzyltetrahydroisoquinoline alkaloids, with 12-O-methylcurine, cissacapine and cycleanine as the main ones. Alkaloids appear to be quite variable within different plant parts and different provenances, as confirmed by the difference in alkaloid patterns between coastal and inland forms of Cissampelos capensis (the morphinane alkaloid salutaridine, for example, is the major leaf alkaloid along the coast but is practically absent from the inland form of the species). The variety of alkaloids identified may contribute to the medicinal value of this species. The data on alkaloidal variation in the species has potential value and practical applications in chemotaxonomy, toxicology and pharmacognosy.     

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.     

Diastereoselective Pomeranz–Fritsch–Bobbitt synthesis of (S)-(−)-O-methylbharatamine using (S)-N-tert-butanesulfinimine as a substrate

The protoberberine-type alkaloid, (S)-(−)-O-methylbharatamine, has been synthesized in six steps involving the addition of laterally lithiated o-toluamide to (S)-N-tert-butanesulfinimine as the crucial process. The target alkaloid was obtained in 24.4% overall yield with 88% ee.     

Aporphine alkaloid contents increase with moderate nitrogen supply in Annona diversifolia Saff. (Annonaceae) seedlings during diurnal periods

Aporphine alkaloids are secondary metabolites that are obtained in low levels from species of the Annonaceae family. Nitrogen addition may increase the alkaloid content in plants. However, previous studies published did not consider that nitrogen could change the alkaloid content throughout the day. We conducted this short-term study to determine the effects of nitrogen applied throughout the diurnal period on the aporphine alkaloids via measurements conducted on the roots, stems and leaves of Annona diversifolia seedlings. The 60-day-old seedlings were cultured with the addition of three levels of nitrogen (0, 30 and 60 mM), and alkaloid extracts were analysed using high-performance liquid chromatography. The highest total alkaloid content was measured in the treatment with moderate nitrogen supply. Further, the levels of aporphine alkaloids changed significantly in the first few hours of the diurnal period. We conclude that aporphine alkaloid content increased with moderate nitrogen supply and exhibited diurnal variation.     

Microbial transformation of the phthalideisoquinoline alkaloid, (-)-beta-hydrastine

The phthalideisoquinoline alkaloid (-)-beta-hydrastine is one of the main active constituents of the medicinal plant, Hydrastis canadensis, which is used in many dietary supplements intended to enhance the immune system. Treatment of hydrastine with the fermentation broth of Polyporous brumalis (ATCC 34487) as a model for mammalian metabolism, gave a new alkaloid, (1S)-hydroxyhydrastine. Structure elucidation was based primarily on NMR and chiroptical studies.     

Chemotaxonomy of the rutaceae—II Extractives of severinia buxifolia (Poir._) Ten.

Leaf extracts of Severinia buxifolia (Poir.) Ten. were found to contain seselin, small amounts of an alkaloid and a new coumarin which was shown by chemical spectroscopic studies to be 5,7-dimethoxy-8-(3′methyl-2′-oxobutyl)coumarin. Extracts of the fruit gave small amounts of seselin, imperatorin, isopimpinelin, bergapten and the same alkaloid as that found in the leaf extracts. Base saponification of the alkaloid gave palmitic acid and an alcohol named severine. Severine in a N-bezoyl-tyramine derivative and was shown to have stucture 16 by chemical and spectroscopic studies.     

Total Synthesis of (−)-(2R)-Dihydromyricoidine

An asymmetric synthesis of the spermidine alkaloid (?)-(2R)-dihydromyricoidine ( 5 ) was performed by employing two ring-enlargement reactions. The chiral center was introduced by a diastereoselective Michael addition of perhydropyridazine ( 7 ) to the α,β-unsaturated ester 6 . The (Z)-C?C bond was obtained by a selective Wittig reaction. The synthetic compound 5 was found to have a negative value for the specific rotation. This is in contrast to that of the natural product reported in the literature. Therefore, as an outcome of this synthesis, the absolute configuration of the natural alkaloid should be inverted to be as shown in structure V .     

Total synthesis of the Securinega alkaloid (-)-secu'amamine A

The first enantioselective total synthesis of the rearranged Securinega alkaloid (-)-secu'amamine A is reported starting from D-proline as the source of absolute chirality. The synthesis requires 15 steps starting from D-proline-derived N-trityl aldehyde 11 and proceeds in approximately 9% overall yield. Key steps include a stereoselective conjugate addition of pyrrolidino enedione 19 to afford indolizidine 24 as the major product and cyclization/lactonization of diketoester 25 to produce tetracycle 26. In addition, 1H NMR NOE studies and X-ray analysis on the synthetic alkaloid have established that the indolizidine moiety is trans-fused.     

Total synthesis of the neotropical poison-frog alkaloid (-)-205B

[reaction: see text]. A stereocontrolled total synthesis of the neotropical poison-frog alkaloid (-)-205B (1) has been achieved, employing a dithiane three-component linchpin coupling, a one-pot sequential construction of the embedded indolizidine ring, and ring-closing metathesis (RCM) to arrive at the novel 8b-azaacenaphthylene ring system comprising the alkaloid. The synthesis proceeded with a longest linear sequence of 19 steps, affording (-)-1 in 5.6% overall yield.     

Stereospecific total synthesis of (±)-strempeliopine

The 18-methylene-1,2-dehydroaspidospermidine (III) was stereospecifically transformed into the schizozygane alkaloid strempeliopine (II) in 16,6 % overall yield.     

BF(3)-Induced rearrangement of aziridino cyclopropanes derived from 2-phenylsulfonyl 1,3-dienes. Application to the total synthesis of (+/-)-ferruginine

Total synthesis of the alkaloid (+/-)-ferruginine (1) has been developed via the 2-phenylsulfonyl 1,3-diene approach. BF(3)-induced rearrangement of the N-protected cyclohexane aziridino cyclopropane 8, derived from its corresponding epoxy cyclopropane, afforded the desired tropane alkaloid skeleton 9 in good yield. Michael addition of nitroethane (as an acyl anion equivalent) and transformation of the nitro group of the adduct 10 to a keto function gave 11. Elimination of benzenesulfinic acid and subsequent replacement of the tosyl group by a methyl group afforded the title compound 1.     

Six-step synthesis of (S)-brevicolline from (S)-nicotine

[reaction: see text] A six-step synthesis of (S)-brevicolline from (S)-nicotine is reported. Regioselective trisubstitution of the pyridine ring of nicotine, followed by successive Suzuki cross-coupling and Buchwald amination reactions, afforded the enantiopure beta-carboline alkaloid, brevicolline.     

Lihouidine, a novel spiro polycyclic aromatic alkaloid from the marine sponge Suberea n. sp. (Aplysinellidae, Verongida)

An investigation of a new species of sponge from the genus Suberea collected at Lihou Reef in the Coral Sea afforded lihouidine, an unprecedented cytotoxic spiro nonacyclic polyaromatic alkaloid. The structure of the alkaloid, which was racemic, was determined by a combination of 1D and 2D NMR techniques and single-crystal X-ray structural analysis.     

Synthesis of (--)-lasubine(I) via a planar chiral [(eta6-arene)Cr(CO)3] complex

Key steps of the synthesis of the Lythracaea alkaloid (--)-lasubine(I) are the formation of an enantiopure planar chiral arylaldehyde tricarbonylchromium complex and highly diastereoselective aza-Diels-Alder cycloaddition and intramolecular radical cyclization reactions to afford a quinolizidinone intermediate. Ketone reduction, desilylation, and decomplexation yield the enantiomerically pure product.     

Synthesis of (±)-aporphine utilizing Pictet-Spengler and intramolecular phenol ortho-arylation reactions

A synthesis of the alkaloid (±)-aporphine is reported. The initial key step of the synthesis involves a Pictet-Spengler cyclization of N-tosyl tyramine with 2-bromophenylacetaldehyde in trifluoroacetic acid. This step was followed by the second strategic transformation a palladium-mediated intramolecular phenol ortho-arylation reaction utilizing tricyclohexylphosphine as co-catalysts in the presence of cesium carbonate. Finally, de-oxygenation of the phenol, removal of the tosyl group and methylation gave the desired alkaloid.     

Concise synthesis of the (+/-)-Nb-desmethyl-meso-chimonanthine

The first total synthesis of the bis-pyrroloindoline alkaloid (+/-)-Nb-desmethyl-meso-chimonanthine, having a pseudo C2-symmetry, was realised in a seven-step convergent sequence without the use of protecting groups.     

A short synthesis of staurosporinone (K-252c)

A new, simple, high-yield synthesis of the indolo[2,3-a]carbazole alkaloid staurosporinone is described.     

The enantioselective total synthesis of a beta-carboline alkaloid, (S)-(-)-dichotomine C

The first enantioselective synthesis of a beta-carboline alkaloid, dichotomine C, possessing antiallergic effects, was achieved by constructing a beta-carboline framework based on the microwave-assisted thermal electrocyclic reaction of a 1-azahexatriene system, followed by the Sharpless asymmetric dihydroxylation.     

Enantioselective fluorination mediated by N-fluoroammonium salts of cinchona alkaloids: first enantioselective synthesis of BMS-204352 (MaxiPost)

We have employed a cinchona alkaloid/Selectfluor-mediated enantioselective fluorination of the oxindole 2 to achieve the first enantioslective synthesis of BMS-204352 (MaxiPost, S-1), an effective opener of maxi-K channels. Fluorination occurred to produce S-1 with 84% ee using the bis-cinchona alkaloid (DHQ)(2)AQN. Recrystallization produced enantiomerically pure (>99% ee) product. Quinidine-mediated fluorination of 2 gave the (R)-antipode of 1 with 68% ee.