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Alkaloid chemistry is no picnic. In fact, when I started my graduate studies, it was often joked that every nitrogen in your natural product would add a year to the time it’d take you to finish your PhD. Ever the empiricist, I found this to be true.

You see, even with careful planning, nitrogen-containing molecules will inevitably throw up roadblocks that’ll send you on lengthy detours or desperately hunting for workarounds. Unprotected amines alone are a challenge – to say nothing of the legendary intractability of guanidines. For one thing, they’re among nature’s strongest bases and nucleophiles. In addition, they make purification by conventional chromatography all but impossible – yes, I’ve tried adding triethylamine! To sidestep these issues, even virtuosic organic chemists will swaddle them with protecting groups to blunt their reactivity but, even so larded, they can still cause havoc with their lone pairs.