1Alkaloid Purification Strategies Using Flash Chromatography

Alkaloids are common compounds derived from natural products. Many alkaloids are also synthesized for their medicinal properties. They are challenging to purify on silica due to their polarity and basic-ity. The use of appropriate solvents and columns allow facile purifica-tion of this class of compounds. Examples are provided for silica, C18, ion exchange, and alternative media such as diol and amine columns. Background Alkaloids include a diverse class of nitrogen containing compounds that often exhibit pharmacological effects. These compounds are often found in plants, although they are also commonly synthesized com-pounds. As these compounds are ubiquitous in medicinal chemistry, strategies to purify this class of compounds is of great interest. Experimental and Results All experiments were run on a CombiFlash ® Rf 200 Flash chroma-tography system (PN 68-5230-006). Pure chemicals were obtained from Sigma-Aldrich (St. Louis, MO). Other details are described in each section below. All columns were RediSep Rf Gold ® packed with spherical 20–40 micron media. 3Silica Strategies Silica is the most common means to purify alkaloids because the media is relatively inexpensive and silica can be used to purify a wide variety of compounds. Choosing appropriate methods to purify alkaloids can be difficult due to the polarity range exhibited by these compounds. Some useful guidelines include: • Less polar alkaloids require less polar solvents such as hexane/ ethyl acetate. These alkaloids have nonpolar substituents or few basic centers (nitrogen). • Alkaloids of intermediate polarity are purified using dichloro-methane and methanol. • Very polar alkaloids can be purified with mobile phases contain-ing a large percentage of methanol or water with RediSep Rf Gold silica. An example of a relatively nonpolar alkaloid is shown in Figure 1. The non-polar substituents on the purine ring allow purification with gradients from 50 to 75 % ethyl acetate1. As the number of substituents decrease, or as they become more polar, dichloromethane and metha-nol are required to elute the compound