strychnine and indole

We describe enantioselective syntheses of strychnos and chelidonium alkaloids. In the first case, indole acetic acid esters were established as excellent partner nucleophiles for enantioselective cooperative isothiourea/Pd catalyzed α-alkylation. This provides products containing indole-bearing stereocenters in high yield and with excellent levels of enantioinduction in a manner that is notably independent of the N-substituent. This led to concise syntheses of (-)-akuammicine and (-)-strychnine. In the second case, the poor performance of ortho-substituted cinnamyl electrophiles in the enantioselective cooperative isothiourea/Ir catalyzed α-alkylation was overcome by appropriate substituent choice, leading to enantioselective syntheses of (+)-chelidonine, (+)-norchelidonine, and (+)-chelamine.

Topics: Alkaloids; Alkylation; Benzophenanthridines; Berberine Alkaloids; Catalysis; Chelidonium; Humans; Indoles; Iridium; Palladium; Sirtuin 1; Stereoisomerism; Strychnine; Strychnos; Thiourea

The total synthesis of the flagship Strychnos indole alkaloid, strychnine, has been accomplished. The developed synthetic sequence features a novel vinylogous 1,4-addition, a challenging iodinium salt mediated silyl enol ether arylation, a palladium-catalyzed Heck reaction, and a streamlined late-stage conversion to strychnine. Furthermore, an application of asymmetric counterion-directed catalysis (ACDC) in the context of target-oriented organic synthesis has been rendered access to an optically active material. The synthetic sequence described herein represents the most concise entry to optically active strychnine to date.

Topics: Alkaloids; Catalysis; Indoles; Palladium; Stereoisomerism; Strychnine

The first chemical syntheses of complex, bis-Strychnos alkaloids (-)-sungucine (1), (-)-isosungucine (2), and (-)-strychnogucine B (3) from (-)-strychnine (4) is reported. Key steps included (1) the Polonovski-Potier activation of strychnine N-oxide; (2) a biomimetic Mannich coupling to forge the signature C23-C5' bond that joins two monoterpene indole monomers; and (3) a sequential HBr/NaBH3 CN-mediated reduction to fashion the ethylidene moieties in 1-3. DFT calculations were employed to rationalize the regiochemical course of reactions involving strychnine congeners.

Topics: Alkaloids; Cyclic N-Oxides; Indole Alkaloids; Indoles; Stereoisomerism; Strychnine; Strychnos

Brucine is a widely prescribed glycine antagonist, but a complete understanding of its metabolic pathway is still lacking. The present work represents the first investigation of in vivo metabolism of brucine in rats using LC-ESI-ion trap-TOF-MS.. A total of 12 Phase I and five Phase II metabolites were tentatively identified. Brucine can be metabolized by hydrolysis, demethylation and methoxylation, in addition to diverse oxidations in a Phase I manner followed by glucuronidation in Phase II metabolism. Both the renal and biliary routes were observed for the excretion of brucine and its metabolites.. Our results update the metabolism and disposition data on brucine, which provides basic information for better understanding of the pharmacological and toxicological activities of brucine-containing medicines.

Topics: Alkaloids; Animals; Bile; Biotransformation; Chromatography, High Pressure Liquid; Glucuronidase; Hydrolysis; Hydroxylation; Indoles; Metabolic Networks and Pathways; Oxidation-Reduction; Rats; Spectrometry, Mass, Electrospray Ionization; Strychnine

Gardovatine (1), the first Strychnos-Strychnos alkaloid with a C3/C7 cleaved backbone, was isolated from twigs and leaves of Gardneria ovate, together with an analogue divarine (2). The structure was established by extensive spectroscopic methods. Both compounds showed potential cytotoxicities against five human cancer cell lines.

Topics: Alkaloids; Cell Line, Tumor; Cell Survival; Drug Screening Assays, Antitumor; Humans; Indole Alkaloids; Indoles; Loganiaceae; Magnetic Resonance Spectroscopy; Molecular Conformation; Plant Leaves; Strychnos

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.

Topics: Alkaloids; Cyclization; Indoles; Iodides; Molecular Structure; Samarium; Strychnos

Topics: Contracture; Electric Stimulation; Electrophysiology; Indoles; Insecta; Kymography; Leg; Muscle Contraction; Muscles; Neuromuscular Junction; Pharmacology; Physiology; Research; Reserpine; Strychnine