A Direct, Early Stage Guanidinylation Protocol for the Synthesis of Complex Aminoguanidine-containing Natural Products

The overall goal of this direct synthetic approach which is applied here to prepare the marine natural product, clavatadine A, is to reduce the number of chemical transformations needed to prepare linear aminoguanidine-containing molecules. This method can be used to prepare natural and engineered compounds quickly and efficiently to further understand their biology which may lead to new and better medicines for human health. The main advantage of early stage guanidinylation is that a mass guanidine can remain intact if an appropriate protecting group strategy is devised to avoid chemo selectivity issues in subsequent reactions.

To begin this procedure weigh 0.933 grams of 2, 4-dibromo homogentisic acid lactone on an analytical balance. Add this solid to a round bottomed reaction flask containing a magnetic stir bar under a nitrogen umbrella. Add 30 milliliters of anhydrous dichloromethane to the flask.