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.     

Nonaqueous CE ESI‐IT‐MS analysis of Amaryllidaceae alkaloids

The Amaryllidaceae are widely distributed medical plants. Lycorine, lycoramine, lycoremine, and lycobetaine are the major active alkaloids in Amaryllidaceae plants. A nonaqueous CE ESI‐IT‐MS method for separation, identification, and quantification of the Amaryllidaceae alkaloids has been developed. The MS^1–3 behavior has been studied and the fragmentation pathways of main fragment ions have been proposed. The effects of several factors such as composition and concentration of buffer, applied voltage, composition, and flow rate of the sheath liquid, nebulizing gas pressure, flow rate, and temperature of drying gas were investigated. Under the optimal conditions, the linear concentration range of these compounds was wide with the correlation coefficient (R²) >0.99. RSDs of migration time and peak areas were <10%. The LODs were <240 ng/mL. The proposed method can be successfully applied to the determination of the related alkaloids in the Lycoris radiata roots.     

Three New C19‐Diterpenoid Alkaloids from Aconitum forrestii

A further study of the alkaloid constituents of Aconitum forrestii led to the isolation of three new C₁₉‐diterpenoid alkaloids, named 14‐acetoxy‐8‐O‐methylsachaconitine ( 1 ), 14‐acetoxyscaconine ( 2 ), and 8‐O‐ethylcammaconine ( 3 ). Their structures were determined by UV, IR, and MS, 1D‐ and 2D‐NMR analyses.     

Asymmetric formal total synthesis of the stemofoline alkaloids: the evolution,development, and application of a catalytic dipolar cycloaddition cascade

A formal synthesis of didehydrostemofoline and isodidehydrostemofoline has been accomplished by preparing an intermediate in the Overman synthesis of these alkaloids from commercially available 2-deoxy-d-ribose. The work presented in this account chronicles the evolution of our explorations to identify the optimal steric and electronic control elements necessary to generate the tricyclic core structure of these alkaloids in a single operation from an acyclic precursor. The key step in the synthesis is a novel dipolar cycloaddition cascade sequence that is initiated by cyclization of a rhodium-derived carbene onto the nitrogen atom of a proximal imine group to generate an azomethine ylide that then undergoes spontaneous cyclization via dipolar cycloaddition. The synthesis features several other interesting reactions, including a Boord elimination to prepare a chiral allylic alcohol, a highly diastereoselective Hirama–Itô cyclization, and a useful modification of the Barton decarboxylation protocol.     

Stereocomplementary Routes to Hydroxylated Nitrogen Heterocycles: Total Syntheses of Casuarine,Australine, and 7‐epi‐Australine

Addition of lithiated 1‐benzyloxyallene to a D ‐arabinose‐derived cyclic nitrone occurred with perfect diastereoselectivity furnishing a bicyclic 1,2‐oxazine derivative, which is an excellent precursor for pyrrolizidine alkaloids hydroxylated at C‐7 with optional configuration at this stereogenic center. Depending on the stage of the N? O bond cleavage and ring re‐closure, 7‐hydroxypyrrolizidines with 7R or 7S configuration were obtained, as a result of completely selective addition reactions occurring complementarily at the bottom or top face of the endocyclic C? C double bond in six‐ and five‐membered B rings, respectively. Applicability of these stereodivergent routes to obtain polyhydroxy pyrrolizidine alkaloids is demonstrated by the efficient syntheses of casuarine and australine as examples of the two classes of diversely configured 7‐hydroxypyrrolizidine alkaloids. An alternative synthesis of australine and two strategies for the preparation of 7‐epi‐australine are also reported, which demonstrate that the stereoselectivity of hydride reduction of an exocyclic C? O double bond is independent of the ring size, occurring preferentially from the top face either in a six‐ or five‐membered ring.     

Towards the Core Structure of Strychnos Alkaloids Using Samarium Diiodide‐Induced Reactions of Indole Derivatives

This report describes the development of a first and second generation approach towards the synthesis of the ABCEG pentacyclic core structure of Strychnos alkaloids. First, we discuss a sequential approach applying a series of functional group transformations to prepare suitable precursors for cyclization reactions. These include attempts of samarium diiodide‐induced cyclizations or a Barbier‐type reaction of a transient lithium organyl, which successfully led to a tetracyclic key building block earlier used for the synthesis of strychnine. Secondly, we account our first steps towards the development of an atom‐economical samarium diiodide‐induced cascade reaction using “dimeric” indolyl ketones as cyclization precursors. In this context, we discuss plausible mechanisms for the samarium diiodide‐induced cascade reaction as well as transformations of the obtained tetracyclic dihydroindoline derivatives.     

Addition of Organometallic Reagents to Chiral N‐Methoxylactams: Enantioselective Syntheses of Pyrrolidines and Piperidines

Enantioselective iridium‐catalyzed allylic substitutions were used to prepare N‐allyl hydroxamic acid derivatives that were suitable for ring‐closing metathesis, giving N‐methoxylactams. Reactions of these derivatives with Grignard or organolithium compounds gave hemiaminals, which could be reduced diastereoselectively via acyliminium intermediates to give cis‐piperidines or cis‐pyrrolidines with substituents in the 2,6‐ or 2,5‐positions, respectively. In addition, compounds with a quaternary carbon center could be synthesized by corresponding reactions with potassium cyanide/AcOH. The procedures were applied in the syntheses of alkaloids (?)‐209D and (+)‐prosophylline.