Solvent effect on pyridine derivatives. Molecular iodine donor-acceptor equilibria. The isoquinoline-I2-organic solvent system and the 2,4-lutidine-I2-organic solvent system

The absorption spectra of isoquinoline-iodine or 2,4-lutidine-iodine solutions in organic solventsn-hexane,n-heptane, cyclohexane, carbon tetrachloride, benzene, toluene, chlorobenzene, ando-dichlorobenzene have been measured and interpreted in terms of the D+I₂=DI₂ equilibrium, where D is isoquinoline or 2,4-lutidine. Values ofK (288–320°K), ΔH^o, and ΔS^o for the reaction were calculated. A correlation between theK values and the solubility parameter of the solvent (Buchowski's relation) has been found.     

Synthesis of stable azomethine ylides by the rearrangement of 1,3-dipolar cycloadducts of 3,4-dihydroisoquinoline-2-oxides with DMAD

1-Aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines were prepared according to a one-pot procedure involving the reaction of 2-(3,4-dimethoxyphenyl)-ethylamine with aromatic aldehydes in TFA at reflux. The tetrahydroisoquinolines were treated with H₂O₂-WO₄²⁻ in methanol at room temperature to give the corresponding 3,4-dihydroisoquinoline-2-oxides. Treatment of these cyclic nitrones with DMAD in toluene at room temperature gave the corresponding isoxazolo[3,2-a]isoquinolines. These compounds were heated in toluene at reflux to give the corresponding ylides in high yields (Method A). The effect of the substituents on the rate of the rearrangement of such compounds prompted us to discuss a new mechanism involving consecutive C-C bond heterolysis and 1,3-sigmatropic shift. A one-pot reaction involving the treatment of the nitrones with equimolar amounts of DMAD in refluxing toluene also gave the ylides (Method B). The structures of the prepared compounds were elucidated by spectral means and elemental analyses.     

Pictet-Spengler reactions catalyzed by Brønsted acid-surfactant-combined catalyst in water or aqueous media

Perfluorooctanesulfonic acid (PFOSA), Brønsted acid-surfactant-combined catalyst, efficiently catalyzes the Pictet-Spengler reactions of β-arylethyl carbamate derivatives with aldehydes in water. The present reaction is accelerated by the addition of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP).     

A synthesis of pyrrolo[2,1-a]isoquinolines through the reaction of activated acetylenes and isoquinoline in the presence of ethyl bromopyruvate

Isoquinoline reacts with ethyl bromopyruvate in the presence of dialkyl acetylenedicarboxylates or diaryloylacetylenes to produce dialkyl 1-(2-ethoxy-2-oxoacetyl)pyrrolo[2,1-a]isoquinoline-2,3-dicarboxylates or ethyl 2-[2,3-diaryloylpyrrolo[2,1-a]isoquinoline-1-yl]-2-oxoacetates in good yields.     

Enantioselective synthesis of axially chiral 1-(1-naphthyl)isoquinolines and 2-(1-naphthyl)pyridines through sulfoxide ligand coupling reactions

Racemic 1-(1′-isoquinolinyl)-2-naphthalenemethanol rac-12 was prepared through a ligand coupling reaction of racemic 1-(tert-butylsulfinyl)isoquinoline rac-7 with the 1-naphthyl Grignard reagent 10. Resolution of rac-12 was achieved through chromatographic separation of the Noe-lactol derivatives 14 and 15, providing (R)-(−)-12 of >99% ee and (S)-(+)-12 of 90% ee. The ligand coupling reaction of optically enriched sulfoxide (S)-(−)-7 (62% ee) with Grignard reagent 10 furnished rac-12, with the absence of stereoinduction resulting from competing rapid racemisation of the sulfoxide 7. Reaction of optically enriched (S)-(−)-7 with 2-methoxy-1-naphthylmagnesium bromide was also accompanied by racemisation of the sulfoxide 7, and furnished optically active (+)-1-(2′-methoxy-1′-naphthyl)isoquinoline (+)-3b in low enantiomeric purity (14% ee). The absolute configuration of (+)-3b was assigned as R using circular dichroism spectroscopy, correcting an earlier assignment based on the Bijvoet method, but in the absence of heavy atoms. Optically active 2-pyridyl sulfoxides were found not to undergo racemisation analogous to the 1-isoquinolinyl sulfoxide 7, with the ligand coupling reactions of (R)-(+)- and (S)-(−)-2-[(4′-methylphenyl)sulfinyl]-3-methylpyridines, (R)-(+)-17 and (S)-(−)-17, with 2-methoxy-1-naphthylmagnesium bromide providing (−)- and (+)-2-(2′-methoxy-1′-naphthyl)-3-methylpyridines, (−)-18 and (+)-18, in 53 and 60% ee, respectively. The free energy barriers to internal rotation in 3b and 18 have been determined, and the isoquinoline (R)-(−)-12 examined as a ligand in the enantioselectively catalysed addition of diethylzinc to benzaldehyde; (R)-(−)-12 was also converted to (R)-(−)-N,N-dimethyl-1-(1′-isoquinolinyl)-2-naphthalenemethanamine (R)-(−)-19, and this examined as a ligand in the enantioselective Pd-catalysed allylic substitution of 1,3-diphenylprop-2-enyl acetate with dimethyl malonate.     

Simultaneous quantification of 11 isoquinoline alkaloids in Corydalis impatiens (Pall.) Fisch by HPLC

Isoquinoline alkaloids are the primary active ingredients of Corydalis, but an analytical method for quality assessment of the active ingredients in Corydalis impatiens (Pall). Fisch has not been reported. A new, simple, and multiple‐component quantification method was developed for the simultaneous quantification of 11 isoquinoline alkaloids including capnoidine, chelianthifoline, bicuculline, protopine, isoapocavidine, apocavidine, cavidine, tetrahydroepiberberine, ochotensimine, tetrahydrocoptisine, and tetrahydrocorysamine in C. impatiens. Separation of the isoquinoline alkaloids was performed on a RP C₁₈ column (150 × 4.6 mm, 5 μm) with potassium dihydrogen phosphate buffer (pH 2.5, adjusted by phosphoric acid)/acetonitrile (53:47, v/v) containing 0.3% sodium dodecyl sulfonate. The flow rate and detection wavelength were set at 1 mL/min and 295 nm, respectively. Full validation of the assay was carried out including linearity, precision, accuracy, stability, LOD, and limit of quantitation. All calibration curves showed a good linear relationship (r > 0.999) in test range. The results demonstrated that the developed method was reliable, rapid, and specific. Six batches of C. impatiens samples from different sources were determined using the established method. The contents of alkaloids ranged from 11.68 to 351.83 μg/g. This method can be applied for quality evaluation and control of C. impatiens. Eleven isoquinoline alkaloids were first reported on simultaneous determination with HPLC.     

A novel multicomponent reaction involving isoquinoline,allenoate and activated ketone

The reaction of isoquinoline and allenoate with activated ketone resulted in a novel three component reaction, affording [1,3]oxazino[2,3-a]isoquinoline derivatives in moderate yields along with moderate diastereoselectivities via 1,4-dipolar cycloaddition. It was also found that when isatins were used as substrates, the regioselectivity of cycloadducts was different from those using ethyl trifluoropyruvate as substrate.     

One-pot synthesis of isoquinoline and related compounds via Cu-mediated tandem cross-coupling and cyclization

One-pot synthetic strategy has been developed to access isoquinolines and its analogs via Cu-mediated tandem cross-coupling and cyclization in good yields under mild reaction conditions. A mixture of suitably substituted α-bromoaldehyde, terminal alkyne, and aq NH₃ in CuI/1,10-phenanathroline catalytic system afforded the 3-substituted isoquinoline regio-selectively in good to excellent yields.     

异喹啉酸衍生物刷型手性键合固定相的制备及在联萘酚衍生物拆分中的应用

在(S)-THIQCA环上引入π 酸基团, 制备了一种新型的刷型手性固定相(CSP), 并用于联萘酚及其衍生物的拆分, 探讨了改性剂对色谱行为的影响.     

Additional Isoquinoline Alkaloids from Lltsea Cubeba

By combination of centrifugal partition chromatography (CPC) and common separation methods, seven additional known bases were isolated and characterized from the reinvestigation of L. cubeba besides three previously isolated bases- isocorydine (10), N-methyllaurotetanine (9), and boldine (2). They are laurolitsine (1), laurotetanine (3), isoboldine (4), norisocorydine (5), N-methyllindcarpine (7), isodomesticine (8), and glaziovine (6). Among these, compound 9 is the most abundant (7.5 × 10^?4) and will be modified for pharmacological tests. This work will be of value for chemotaxonomy.