Concise Construction of the ACDE Ring System of Calyciphylline A Type Alkaloids by a [5+2] Cycloaddition

A concise route for construction of the ACDE ring skeleton in calyciphylline A type alkaloids was developed using an intramolecular [5+2] cycloaddition reaction of an oxidopyrylium species bearing a tetrasubstituted olefin. Key to the success of this reaction was the combination of acid and base, which accelerated the construction of this skeleton containing a spiro ring and vicinal quaternary carbon centers. The resultant tricyclic ADE ring compound was converted to an ACDE ring model through C−H oxidation and an aza-Wittig reaction.     

Access to Enantiopure Advanced Intermediates en Route to Madangamines

The synthesis of enantiopure ABCE and ABCD tetracyclic advanced intermediates en route to madangamine alkaloids and studies for the construction of the triunsaturated 15-membered D ring of madangamine B and the saturated 13-membered D ring of madangamine E are reported.     

Pharmacokinetics of monoester‐diterpenoid alkaloids in myocardial infarction and normal rats after oral administration of Sini decoction by microdialysis combined with liquid chromatography–tandem mass spectrometry

Monoester‐diterpenoid alkaloids are the main bioactive components of Sini decoction, which is a well‐known traditional Chinese medicine formula for the treatment of myocardial infarction (MI) and heart failure in China. In this work, an ultra‐high‐performance liquid chromatography–mass spectrometry combined with microdialysis method was successfully established and applied for investigating for the first time comparative plasma pharmacokinetics of three monoester‐diterpenoid alkaloids (benzoylmesaconitine, benzoylaconitine and benzoylhypacoitine) in normal and MI rats after oral administration of Sini decoction. The statistical results of pharmacokinetic parameters demonstrated that benzoylmesaconitine, benzoylaconitine and benzoylhypacoitine showed lower peak concentration, longer half‐life, smaller area under the concentration–time curve, slower clearance, time to peak concentration and mean residence time in MI rats than in normal rats (p < 0.05), which indicated that monoester‐diterpenoid alkaloids exhibited lower systemic exposure and slower elimination in the MI rats. The results provided the experimental basis for understanding the metabolic fate and therapeutic effects of Sini decoction.     

Synthesis of Azabicyclic Building Blocks for Daphniphyllum Alkaloid Intermediates Featuring N‐Trichloroacetyl Enamide 5‐endo‐trig Radical Cyclizations

A general procedure is reported for the synthesis of cis ring fused azapolycyclic compounds bearing an all‐carbon quaternary stereocenter at the ring fusion and an adequate functionalization for the assembly of new rings leading to advanced synthetic intermediates for Daphniphyllum alkaloid synthesis. The key carbon?carbon bond‐forming step in this approach is a radical cyclization of an N‐cycloalkenyl trichloroacetamide derivative involving a tetrasubstituted enamide to achieve polyfunctionalized lactams.     

A review on analytical methods for natural berberine alkaloids

Berberine alkaloids, a group of protoberberine alkaloids under the classification of isoquinoline alkaloids, include berberine, coptisine, palmatine, columbamine, dehydrocorydaline, jatrorrhizine, and epiberberine from natural sources. Studies have shown that berberine alkaloids have various pharmacological functions, such as antibacterial, antiviral, blood pressure‐lowering, hypoglycaemic, antiarrhythmia, and anticancer effects. Therefore, it is worthwhile to develop analytical methods to investigate the pharmacokinetics and activity mechanisms of berberine alkaloids and to study berberine alkaloids more comprehensively. Current analytical methods for berberine alkaloids include liquid chromatography, thin‐layer chromatography, ultraviolet spectroscopy, capillary electrophoresis, and gas chromatography. The most widely used detection method is mass spectrometry. In order to provide a systematic and comprehensive summary and to serve as a reference for the future pharmacokinetics studies and analysis of berberine alkaloids, analytical methods for natural berberine alkaloids that have been used in the past ten years are reviewed here.     

Study on the racemization of synephrine by off-column chiral high-performance liquid chromatography

In this study, the racemization kinetic parameters of R-(−)-synephrine, the active phenethylamine alkaloid of Citrus aurantium L., were determined by means of an off-column HPLC method. Enantioseparation was carried out in different buffer solutions and solvents on a chiral stationary phase (CSP) with cellobiohydrolase as the chiral selector (Chiral-CBH, 100 mm × 4.0 mm i.d., 5 μm). The mobile phase was 10 mM sodium phosphate buffer (pH 6.0)-2-propanol (95:5, w/w), with 50 μM disodium EDTA, at 0.8 mL/min. The column was thermostatted at 20 °C and detection was set at 225 nm. The influence of pH value, ionic strength, temperature and addition of organic modifier on the rate constant, the half-life of racemization and the free energy barrier of racemization of R-(−)-synephrine were determined. Among the different chemical and physical parameters evaluated as affecting the racemization of naturally occurring R-(−)-synephrine, pH, temperature and addition of an organic co-solvent appear to have the strongest effect, while ionic strength does not exert a significant influence on the racemization rate. The results of the present study indicated that synephrine racemization is possible at high temperature at both acidic and basic pH values; therefore, the extraction procedure of R-(−)-synephrine from the plant material should be carried out under specific conditions to preserve the stereochemical integrity and the biological activity of this secondary metabolite.     

Synthesis of functional 2-substituted 4-phenyl-9H-pyrimido[4,5-b]indoles

A method was developed for the synthesis of 2-oxo-4-phenyl-2,3-dihydro-9H-pyrimido[4,5-b]indole as well as of 2-chloro- and 2-nitramino-4-phenylpyrimido[4,5-b]indoles. The replacement of the chlorine atom in 2-chloropyrimidoindole gave rise to a number of its functional derivatives (morpholino, azido, and cyano). The reaction of 2-chloro-substituted pyrimidoindole with hydrazine hydrate and catalytic hydrogenation of 2-nitraminopyrimidoindole were studied.     

超声波辐射下β-吲哚衍生物的合成

在超声波下以吲哚、芳香醛、丙二酸亚异丙酯为原料一锅法合成了β-吲哚衍生物——5-[(3-吲哚基)．芳甲基]-2,2-二甲基-1,3-二氧六环4,6-二酮,其结构经IR和1H NMR确认。     

On the reduction of 1-aryl-2-oxo-1,2,3,6-tetra-hydro[1,4]diazepino[6,5-<Emphasis Type="Italic">b</Emphasis>]indole 4-oxides

Electrochemical reduction of 1-aryl-2-oxo-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole 4-oxides, 2-oxo-1-phenyl-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole, and 2-oxo-1-phenyl-1,2,3,4,5,6-hexahydro[1,4]diazepino[6,5-b]indole was studied. The results obtained were compared with previous data for the reduction of 4-oxides with formamidinesulfinic acid.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2715–2718, December, 2004.     

Radical amination with sulfonyl azides: a powerful method for the formation of C-N bonds

A novel reaction for the introduction of an azide moiety by means of a mild radical process is currently under development. Sulfonyl azides are suitable azidating agents for nucleophilic radicals, such as secondary and tertiary alkyl radicals. More electrophilic radicals, such as enolate radicals, do not react with sulfonyl azides. This feature allowed the development of efficient intra- and intermolecular carboazidations of olefins. Due to the versatility of the azido group, this reaction has an important synthetic potential, as already demonstrated by the preparation of the core of several alkaloids, particularly those containing an amino-substituted quaternary carbon center, such as FR901483.