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Fresh water cyanobacterial algal blooms represent a major health risk because these organisms produce cylindrospermopsin, a toxic, structurally complex, zwitterionic uracil-guanidine alkaloid recognized by the EPA as a dangerous drinking water contaminant. At present, the ability to detect and quantify the presence of cylindrospermospin in water samples is severely hampered by the lack of an isotopically labeled standard for analytical mass spectrometry. Herein, we present a concise, scaled total synthesis of 15N cylindrospermosin from 15N ammonium chloride, which leverages a unique stereoselective intramolecular double conjugate addition step to assemble the tricyclic guanidine core. In addition to providing the first pure isotopically labeled probe for precise quantification of this potent biotoxin in fresh water sources, our results demonstrate how unique constraints associated with isotope incorporation compel novel solutions to synthesis design. [ABSTRACT FROM AUTHOR]

Pyridines were found to be a convenient nucleophile in the copper(I)-catalyzed synthesis of N -tosyl-4-iminoquinolizines from 2-pyridyl compounds. Intramolecular cyclization of an in situ generated ketenimine and a tethered pyridine, followed by a base-promoted oxidation, affords the desired products in moderate to good yields under mild reaction conditions. [ABSTRACT FROM AUTHOR]

Ketenimines generated in situ from 2-pyridyl compounds and azide (II) undergo an intramolecular cyclization reaction to yield iminoquinolizines. [ABSTRACT FROM AUTHOR]

A method for a directed stereoselective guanidinylation of alkenes is described. The guanidine unit can be delivered as an intact fragment by a hydroxy or carboxy group, usually with a high level of stereocontrol. After the guanidine delivery, the directing group can be cleaved under exceptionally mild conditions, typically by alcoholysis in the presence of acetic acid. Broad functional group tolerance and mild reaction conditions for the cycloguanidilation suggest applications in medicinal chemistry and natural products synthesis. [ABSTRACT FROM AUTHOR]